Multiple SclerosisPhase 3ORACLE MSNCT00725985
Oral Cladribine in Early Multiple Sclerosis (MS)
A Phase 3 study testing Cladribine and Rebif® new formulation (RNF) in people with Multiple Sclerosis, run by EMD Serono Research & Development Institute, Inc. at 158 sites in 34 countries.
Trial summary
A randomized, double-blind, clinical trial to assess the safety and efficacy of two doses of oral cladribine versus placebo in participants who had a first clinical demyelinating event (clinically isolated syndrome). Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Cladribine and Rebif® new formulation (RNF)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 617 participants
- Where
- 158 sitesin 34 countries
- Study dates
- 31 Dec 2008to 30 Apr 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male or female between 18 and 55 years old, inclusive
- Weighed between 40 to 120 kilogram (kg), inclusive
- Participant has experienced a single, first clinical event suggestive of MS within 75 days prior to the Screening visit, (clock starts 24 hours after onset). The event must be a new neurological abnormality present for at least 24 hours, either mono- or polysymptomatic
- Participant has at least two clinically silent lesions on the T2-weighted MRI scan, at screening, with a size of at least 3 millimeter (mm), at least one of which is ovoid or periventricular or infratentorial on screening MRI
- Participant has EDSS 0 - 5.0 at Screening
- Participant has no medical history or evidence of latent tuberculosis infection (LTBI) or active tubercular disease, as evidenced by the Mantoux tuberculosis (TB) skin test or a comparable sensitive test according to local regulations/guidelines (if the Mantoux test is not available), and/or a chest X-ray
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- Participant has normal hematological parameters at Screening, as defined by the central laboratory that performed all the assessments
- If female, she must:
- be neither pregnant nor breast-feeding, nor attempting to conceive and
- use a highly effective method of contraception throughout the entire duration of the study and for 90 days following completion of the last dose of study medication. A highly effective method of contraception is defined as those which result in a low failure rate (that is less than 1 percent per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence or vasectomized partner, or
- be post-menopausal or surgically sterilized (Note: for Danish sites only, participants should use a hormonal contraceptive or intrauterine device for the duration of the trial)
- Male participants must be willing to use contraception to avoid impregnating partners throughout the study, and for 90 days following the last dose of study medication
- Be willing and able to comply with study procedures for the duration of the study
- Participant has to provide written informed consent voluntarily, including, for United states of America (USA), participant authorization under Health Insurance Portability and Accountability Act (HIPAA), prior to any study-related procedure that is not part of normal medical care
- Participant has refused any treatment already available for clinically isolated syndrome (CIS) such as interferons or glatiramer acetate, at the time of entry into the Initial Treatment Period of this study
Who cannot join
- Participant has a diagnosis of MS (per McDonald criteria, 2005)
- Participant has any other disease that could better explain the participant's signs and symptoms
- Participant has complete transverse myelitis or bilateral optic neuritis
- Participant using or has used any other approved MS disease modifying drug (DMD)
- Participant has used any investigational drug or undergone an experimental procedure within 12 weeks prior to Study day 1
- Participant received oral or systemic corticosteroids or adrenocorticotropic hormone (ACTH) within 30 days prior to screening MRI. The MRI had to be performed 30 days after the oral or systemic corticosteroids or ACTH treatment. In case this interfered with MRI timing the screening period could be extended accordingly.
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- Participant has abnormal total bilirubin, or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or alkaline phosphatase greater than 2.5 times the upper limit of normal
- Participant suffered from current autoimmune disease other than MS
- Participant suffered from psychiatric illness (including history of, or concurrent, severe depressive disorders and/or suicidal ideation) that in the opinion of the investigator creates undue risk to the participant or could affect compliance with the study protocol
- Participant suffered from major medical illness such as cardiac (for example angina, congestive heart failure or arrhythmia), endocrinologic, hepatic, immunologic, metabolic, renal, pulmonary, gastrointestinal, dermatologic, or other major disease that would preclude the administration of oral cladribine
- Participant has a history of seizures not adequately controlled by medications
- Participant has a known allergy to cladribine, interferon-beta, the excipient(s) of the study medications, or to gadolinium- diethylenetriamine penta-acetic acid (DTPA)
- Participant has any renal condition that would preclude the administration of gadolinium (for example acute or chronic severe renal insufficiency (glomerular filtration rate [GFR] less than 30 milliliter per minute per 1.73 square meter [mL/min/1.73 m^2])
- Participant has a history of chronic or clinically significant hematological abnormalities
- Participant has a history of active or chronic infectious disease or any disease that compromises immune function (for example human immunodeficiency virus positive [HIV+], human T-lymphotrophic virus [HTLV-1], Lyme disease, latent tuberculosis infection [LTBI] or TB, insulin-dependent diabetes).
- Participant has previously been screened in this study (signed an informed consent) and then withdrawn
- Participant has received any immunomodulatory or immunosuppressive therapy) at any time prior to Study Day 1, including, but not limited to, the following products: any interferon, glatiramer acetate (Copolymer I), cyclophosphamide, cyclosporine, methotrexate, linomide, azathioprine, mitoxantrone, teriflunomide, laquinimod, cladribine, total lymphoid irradiation, anti-lymphocyte monoclonal antibody treatment (for example natalizumab, alemtuzumab/Campath, anti-cluster of differentiation 4 [CD4]), intravenous immunoglobulin G (IVIG), cytokines or anti-cytokine therapy
- Participant has received experimental MS treatment
- Participant has a history of alcohol or drug abuse
- Participant has intolerance or any contraindication to both paracetamol (acetaminophen) and ibuprofen
- Participant has inability to administer subcutaneous injections either by self or by caregiver
- Participant has prior or current malignancy (with the exception of in situ basal or squamous cell skin cancer surgically removed without recurrence for at least five years)
- Participant has a positive stool hemoccult test at Screening
Trial locations and contacts
158 sites in 34 countries.
158 sites in 34 countries
Russia25 sites
Municipal Healthcare Institution "City Clinical Hospital #3"
Chelyabinsk
State Healthcare Institution "Kaluga Regional Hospital"
Kaluga
State Medical Institution "Republican Rehabilitation Clinic of Tatarstan Ministry of Health"
Kazan'
State Healthcare Institution "Kemerovo Regional Clinical Hospital"
Kemerovo
State Medical Institution " Jursk Regional Clinical Hospital"
Kursk
Moscow State Healthcare Institution City Clinical Hospital #11
Moscow
Non-State Healthcare Institution "Central Clinical Hospital #2 named after N.A. Semasko of Russian Railways"
Moscow
State Educational Institute of Higher Professional Education "I.M. Sechenov Moscow Medical Academy of Roszdrav" Russia based on A. Ya. Kozhevnikov Nervous Disease Clinic
Moscow
Municipal Treatment Prophylactic Institution "City Hospital #33"
Nizhny Novgorod
Federal State Institution " Siberian Reginal Medical Center of Roszdarv"
Novosibirsk
State institution Science Research Institute Clinical and Experimental Lymphology of Russian Academy of Medical Sciences
Novosibirsk
State Educational Institute of Higher Professional Education "Rostov State Medical University of Roszdrav"
Rostov-on-Don
State Healthcare Institution "Rostov Region Clinical Hospital"
Rostov-on-Don
Institute of Human Brain of Russian Academy of Science Dept. of Multiple Sclerosis
Saint Petersburg
International Clinic and Hospital, Neurology
Saint Petersburg
St. Petersburg State Healthcare Institution "Multifield City Hospital #2"
Saint Petersburg
State Educational Institution of Higher Professional Education "Military Medical Academy named after S. M. Korov of Dept of Defense of Russian Federation based on Clinic of Neurology of State Institution
Saint Petersburg
State Educational Institution of Higher Professional Education "Samara State Medical University of Roszdrav" on State Healthcare Institution "Samara Regional Clinical Hospital named after M. I. Kalinin"
Samara
State Educational Institution of Higher Professional Education "Saratov State Medical University of Roszdrav" based on Clincial Hosptial #3 of Saratov State Medical University
Saratov
Regional State Healthcare Institution "State Smolensk Region Clinical Hospital"
Smolensk
State Educational Institution of Higher Professional Education "Siberian State Medical University of Roszdrav"
Tomsk
Closed joint-stock society Medical sanitary unit "Nephtaynik" based the hospital
Tyumen
Vladimir Regional State Healthcare Institution "Regional Clinical Hospital"
Vladimir
Municipal Healthcare Institution "Yaroslavi Clinical Hospital #8"
Yaroslavl
State Healthcare Institution "Sverdlovsk Regional Clinical Hospital #1"
Yekaterinburg
United States24 sites
Upstate Clinical Research LLC 3
Albany, New York
MS Center of Atlanta
Atlanta, Georgia
Neurology and Sleep Medicine
Bethlehem, Pennsylvania
Carolinas Medical Center
Charlotte, North Carolina
University of Cincinnati
Cincinnati, Ohio
Michigan Neurology Associates
Clinton Township, Michigan
University of Colorado at Denver Health Sciences
Denver, Colorado
Bruce Hughes West Building
Des Moines, Iowa
Henry Ford Hospital
Detroit, Michigan
Meritcare Neuroscience Center Neurology
Fargo, North Dakota
Fort Collins Neurology
Fort Collins, Colorado
Dennis Dietrich
Great Falls, Montana
Neurological Specialists of Long Island
Great Neck, New York
MS Center of Brevard MIMA Centry Research Associates
Melbourne, Florida
University of Minnesota
Minneapolis, Minnesota
Multiple Sclerosis Center of Northeastern NY
New York, New York
Multiple Sclerosis Center Drive, Neurology Suite 701
Newport Beach, California
MS Center of Oklahoma
Oklahoma City, Oklahoma
Comprehensive MS Care Clinic at South Shore Multiple Sclerosis
Patchogue, New York
Hope Research Institute Medical Plaza LLC Desert Hills
Phoenix, Arizona
Swedish Medical Center Cherry Hill
Seattle, Washington
University of Medicine and Dentistry of New Jersey School of Neurology
Stratford, New Jersey
Neurology & Neurological Association of Tacoma
Tacoma, Washington
University of South Florida
Tampa, Florida
Italy17 sites
Ospedale Regionale Torrette
Ancona
Università de Bari
Bari
Ospedale Binaghi Centro Sclerosi Multipla
Cagliari
Azienda Ospedaliera Garibaldi
Catania
Dipartimento di Neuroscienze
Catania
Università G. D'Annunzio
Chieti
Ospedale San Antonio Abate
Gallarate
Universita degli Studi di Genova
Genova
Ospedale e casa di riposo P. Richiedei
Gussago
Ospedale San Raffaele
Milan
Dipartimento di Scienze Neurologiche
Naples
Azienda Sanitaria Ospedaliera San Luigi Gonzaga
Orbassano
Villa Sofia Hospital Azienda Ospedaliera Villa Sofia P.zza Salerno e Resuttana 1
Palermo
Istituto Neurologico C. Mondino
Pavia
Azienda Ospedaliera S. Camillo Forlanini
Roma
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
Roma
Università di Roma La Sapienza
Roma
Bulgaria9 sites
Military Medical Academy- Sofia (MMA)
Pleven
MBAL Rousse AD 1st
Rousse
Central Clinic Hospital
Sofia
Military Medical Academy
Sofia
National Heart Hospital
Sofia
Second MHAT
Sofia
Tokuda Hospital
Sofia
University Hospital St Naum
Sofia
Medical Centre Centromed 2000
Veliko Tarnovo
Poland9 sites
10 Wojskowy Szpital Kliniczny
Bydgoszcz
Wojewodzki Szpital Specjalistyczny im. M. Kopernika
Gdansk
Niepubliczny Zespol Opieki Zdrowotnej
Krakow
Medical Academy of Lodz
Lodz
Panstwowy Szpital Kliniczny
Lublin
Wojewodzki Szpital Specjalistyczny Oddział Neurologii z Pododdziałem Udarowym
Olsztyn
Medical Academy
Poznan
Medical Academy II
Warsaw
Medical Academy
Warsaw
Czechia6 sites
Faculty Hospital Brno
Brno
Neurological dept of Faculty
Hradec Králové
Fakultní nemocnice s poliklinikou Ostrava
Ostrava
Faculty Hospital Motol
Prague
Klinika Vseobecne
Prague
Nemocnice Teplice
Teplice
India6 sites
M S Ramaiah Medical College Hospital
Bangalore, Karnataka
St.John's Medical College and Hospital
Bangalore, Karnataka
Kovai Medical Centre and Hospital
Coimbatore
Amrita Institute of Medical Sciences and Research
Kochi, Kerala
Sanjay Gandhi Post Graduate Institute of Medical Sciences
Lucknow
Mallikatta Neuro and Research Centre
Mangalore
Finland5 sites
HUS Hyvinkaa Central Hospital
Hyvinkää
OYKS Neurologian Klinikka
Oulu
Neurologian Klinikka Seinajoen Keskussairaala
Seinäjoki
Tampere University Hospital
Tampere
Turun Yliopistollinen Keskussairaala Rakennus 3 1
Turku
South Korea5 sites
National Cancer Center, Department of Neurology,
Gyeonggi-do
Department of Neurology, 50 Ilwon-dong, Gangnam-gu
Seoul
Department of Neurology, Asan Medical Center, 388-1 Pungnap 2-dong, Songpa-gu
Seoul
Seoul National University Hospital, Department of Neurology
Seoul
Yonsei University Medical Center, Department of Neurology, Yonsei University Medical Center
Seoul
Belgium4 sites
Algemeen Ziekenhuis St Jan
Bruges
Cliniques Universitaires St-Luc
Brussels
Hopital Erasme
Brussels
CHU de Liege - Domaine Universitaire du Sart Tilman,
Liège
Portugal4 sites
Hospital Fernando da Fonseca
Amadora
Hospitais da Universidade de Coimbra
Coimbra
Hospital de Santa Maria
Lisbon
Centro Hospitalar de Coimbra
S. Martinho Do Bispo
Romania4 sites
"Dr. Carol Davilla" Military Clinical Hospital
Bucharest
Centrul Medical SANA
Bucharest
Spitalul Clinic Judetean Mures
Târgu Mureş
County Hospital Timisoara
Timișoara
France3 sites
CHU de Lille
Lille
CHU de Nantes
Nantes
American Memorial Hospital
Reims
Georgia3 sites
David Tatishvili Medical Center
Tbilisi
Medical Center Health
Tbilisi
S. Khechinashvili Tbilisi State Medical University
Tbilisi
Serbia3 sites
Clinical Centre of Serbia
Belgrade
Hospital for Prevention and Treatment of Cerebro-Vascular Diseases
Belgrade
Clinical Centre Niš
Niš
Sweden3 sites
Sahlgrenskasjukhuset
Gothenburg
Karolinska University Hospital
Stockholm
Umea University Hospital
Umeå
Ukraine3 sites
State Established "Institute of Neurology, Psychiatry and Narcology of the AMS of Ukraine", Depart of Neurinfections and Multiple Sclorosis
Kharkiv
Institue for Clinical Radiology of the State Establishment "Research Centre for Radiation Medicine of the AMS of Ukraino" Depart of Radiation Psychoneurology
Kiev
Vinnylsia Regional Psychoneurological Hosptial Named After O. I Yushchenko, Neurological Depart, Vinnytsia National Medical University Named After M. I. Pirogov, Chair of Neurology
Vinnitsa
Argentina2 sites
Instituto Medico Rodriguez Alfici
Godoy Cruz
Fundacion Rosarina de Neurorehabilitacion
Rosario
Croatia2 sites
General Hospital Varazdin
Varaždin
University Hospital Zagreb
Zagreb
Estonia2 sites
East Tallinn Central Hospital
Tallinn
West Tallinn Central Hospital
Tallinn
Germany2 sites
Universitaetsklinikum und Medizinische Fakultaet Heidelberg
Heidelberg
Philipps-Universitaet Marburg
Marburg
Norway2 sites
Helse Bergen HF Kvinneklinikken Haukeland Universitetssykehus Jonas
Bergen
Regionsykehuset I Trondheim, Nevrologisk avd.
Trondheim
Spain2 sites
Hospital Reina Sofia Cordoba
Córdoba
Hospital Universitario Nuestra Senora de la Candelaria
Santa Cruz de Tenerife
Taiwan2 sites
Taipei Veterans
Taipei
Chang Gung Medical Foundation- Linkou Branch No5
Taoyuan
Turkey (Türkiye)2 sites
Dokuz Eylul University
Izmir
Ondokuz Mayis Universitesi
Samsun
Bosnia and Herzegovina1 site
Clinical Center University of Sarajevo
Sarajevo
About this study
Official title: A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center Clinical Trial of Oral Cladribine in Subjects With a First Clinical Event at High Risk of Converting to MS
A randomized, double-blind, clinical trial to assess the safety and efficacy of two doses of oral cladribine versus placebo in participants who had a first clinical demyelinating event (clinically isolated syndrome). Participants in either the cladribine or placebo group may also enter treatment periods with open-label interferon-beta or open-label cladribine depending upon the disease status. The primary objective of this study is to evaluate the effect of two dosage regimens of oral cladribine versus placebo on the time to conversion to multiple sclerosis (MS) (from randomization) according to the Poser criteria in participants with first clinical demyelinating event at high risk of converting to MS.
Read the detailed description
This will be a randomized, double blind, three-arm, placebo-controlled, multi-center trial to evaluate the safety and efficacy of oral cladribine versus placebo in the treatment of participants who have sustained a first clinical demyelinating event within 75 days prior to the Screening. Participants must have a minimum of 2 clinically silent lesions on the Screening magnetic resonance imaging (MRI).
The study will include a pre-study evaluation period (Screening period: between 10 and 28 days prior to the start of treatment with blinded study medication (oral cladribine or placebo).
Depending upon the clinical course of their MS, participants will then proceed from the ITP to either the Maintenance Treatment Period (with open-label interferon-beta treatment) or LTFU period (with either open-label low-dose cladribine or no additional treatment (if no progression to MS has been noted after the initial treatment period). The single primary endpoint for the overall study, which will be determined during the ITP, is time to conversion to MS (from randomization), according to the Poser criteria.
For every participants, eligibility for study enrollment and entry into each of the study periods, and diagnosis of conversion to either McDonald MS or CDMS must be confirmed and approved by a Sponsor appointed study Adjudication Committee.
- Conditions
- Multiple Sclerosis
- Being tested
- Cladribine, Placebo, Rebif® new formulation (RNF)
- Keywords
- Clinically Isolated Syndrome (CIS), Early MS, Multiple Sclerosis
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CladribineDrug
Cladribine tablets were administered until CDMS conversion, whichever occur first.
PlaceboDrug
Placebo matched to cladribine tablets were administered.
Rebif® new formulation (RNF)Drug
Participants who converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received RNF subcutaneously at a dose of 44 microgram (mcg) three times a week. Participants who converted to CDMS during long-term follow-up (LTFU) period, received RNF subcutaneously at a dose of 44 mcg three times a week.
| Study group | Role | What they receive |
|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | Experimental | Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 milligrams per kilograms (mg/kg) during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first. Receives: Drug: Cladribine; Drug: Rebif® new formulation (RNF) |
| Cladribine 3.5 mg/kg (ITP) | Experimental | Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first. Receives: Drug: Cladribine; Drug: Rebif® new formulation (RNF) |
| Placebo (ITP) | Placebo comparator | Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first. Receives: Drug: Placebo; Drug: Rebif® new formulation (RNF) |
| Cladribine 5.25 mg/kg, Rebif (OLMP) | Experimental | Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants. Receives: Drug: Cladribine; Drug: Rebif® new formulation (RNF) |
| Cladribine 3.5 mg/kg, Rebif (OLMP) | Experimental | Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants. Receives: Drug: Cladribine; Drug: Rebif® new formulation (RNF) |
| Placebo, Rebif (OLMP) | Experimental | Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants. Receives: Drug: Placebo |
| Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU) | Experimental | Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU. Receives: Drug: Cladribine; Drug: Rebif® new formulation (RNF) |
| Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU) | Experimental | Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU. Receives: Drug: Cladribine; Drug: Rebif® new formulation (RNF) |
| Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU) | Experimental | Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU. Receives: Drug: Placebo |
| Cladribine 5.25 mg/kg, Rebif (LTFU) | Experimental | Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU. Receives: Drug: Cladribine; Drug: Rebif® new formulation (RNF) |
| Cladribine 3.5 mg/kg, Rebif (LTFU) | Experimental | Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU. Receives: Drug: Cladribine; Drug: Rebif® new formulation (RNF) |
| Placebo, Rebif (LTFU) | Experimental | Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
ITP: Time to Clinically Definite Multiple Sclerosis (CDMS) Conversion Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS
CDMS according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to Multiple Sclerosis [MS]) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (>=) 1 point if baseline EDSS was between >= 1.0 and less than or equal to (=<) 4.5; or >= 1.5 points if baseline EDSS was 0, or >= 0.5 if baseline EDSS >= 5.0 over a period of at least 3 months. Kaplan-Meier estimates were provided for of the cumulative (cum.) percentage (%) of participants with CDMS over time. The probability of patients remaining event-free over time (from randomization) in each of the three treatment groups was displayed in the form of survival curves estimated using the non-parametric Kaplan-Meier method.
Measured: ITP: Baseline up to Week 96
Secondary outcomes (48)
ITP: Time to Develop Multiple Sclerosis (MS) Conversion According to the Revised McDonald Criteria (2005) Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With McDonald MS
The McDonald criteria use dissemination in time and space established by magnetic resonance imaging (MRI) findings to provide a clinical diagnosis for MS. Dissemination in time is established by a new time constant 2 (T2) or gadolinium enhanced (Gd+) lesion found on a repeat MRI. Dissemination in space is established by the presence of any 3 of the following: 1 Gd+ lesion or 9 T2 bright lesions if there is no enhancement; greater than or equal to 1 infratentorial lesion; greater than or equal to 1 juxtacortical lesion; greater than or equal to 3 periventricular lesions. Kaplan-Meier estimates were provided for the cum. percentage (%) of participants with McDonald MS over time.
Measured: ITP: Baseline up to Week 96
ITP: Number of Combined Unique Active (CUA) Lesions, New or Enlarging Time Constant 2 (T2) Lesions, and New or Persisting Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan
Number of CUA lesions, new or enlarging T2 lesions, and new or persisting T1 Gd+ lesions were measured by using magnetic resonance imaging (MRI) scans.
Measured: ITP: Baseline up to Week 96
OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression
EDSS progression is based on a standardized neurological exam and focuses on symptoms that commonly occur in Multiple Sclerosis (MS). Overall scores ranges from 0.0 (normal) to 10.0 (death due to MS). A sustained progression on EDSS score was defined as an EDSS progression confirmed into two consecutive assessment. Probability of disability progression at different time points was estimated using Kaplan-Meier method on the time to disability progression defined as the time from randomization to first EDSS increase.
Measured: OLMP: Day 1, 90, 180, 270, 360, 450, 540, 630, 720 and 810
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Multiple Sclerosis (MS) According to the 2005 McDonald Criteria
The McDonald criteria use dissemination in time and space established by magnetic resonance imaging (MRI) findings to provide a clinical diagnosis for MS. Dissemination in time is established by a new time constant 2 (T2) or gadolinium enhanced (Gd+) lesion found on a repeat MRI.
Measured: Time from Randomization up to 1217 days
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria
CDMS according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (>=) 1 point if baseline EDSS was between >= 1.0 and less than or equal to (=<) 4.5; or >= 1.5 points if baseline EDSS was 0, or >= 0.5 if baseline EDSS >= 5.0 over a period of at least 3 months.
Measured: Time from Randomization up to 1217 days
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria
CDMS according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (>=) 1 point if baseline EDSS was between >= 1.0 and less than or equal to (=<) 4.5; or >= 1.5 points if baseline EDSS was 0, or >= 0.5 if baseline EDSS >= 5.0 over a period of at least 3 months.
Measured: Time from Randomization up to 1217 days
ITP: Percentage of Participants Converting to Clinically Definite Multiple Sclerosis (CDMS) as Per Poser Criteria
Clinically definite multiple sclerosis (CDMS) according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (>=) 1 point if baseline EDSS was between >= 1.0 and less than or equal to (=<) 4.5; or >= 1.5 points if baseline EDSS was 0, or >= 0.5 if baseline EDSS >= 5.0 over a period of at least 3 months. The percentage of participants who converted to CDMS are reported here.
Measured: ITP: Baseline up to week 96
ITP: Percentage of Participants Converting to McDonald Multiple Sclerosis (MS) (2005)
Percentage of participants converting to mcDonald multiple sclerosis (2005) were reported.
Measured: ITP: Baseline up to week 96
ITP: Number of New or Persisting Gd-enhanced Lesions
Number of new or persisting Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
Measured: ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96
OLMP: Number of New or Persisting Gd-enhanced Lesions
Number of new or persisting Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
Measured: OLMP: Baseline, Week 24, 48, 72 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions
Number of new or persisting Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
Measured: LTFU: Baseline, Week 13, 24 and 36
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions
Number of new or persisting Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
Measured: LTFU: Baseline, Week 13, 24, 36 and 48
ITP: Number of New or Enlarging T2 Lesions
Number of new or enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans.
Measured: ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96
OLMP: Number of New or Enlarging T2 Lesions
Number of new or enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans.
Measured: OLMP: Baseline, Week 24, 48, 72 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions
Number of new or enlarging T2 Lesions were measured by using magnetic resonance imaging (MRI) scans.
Measured: LTFU: Baseline, Week 13, 24 and 36
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions
Number of new or enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans.
Measured: LTFU: Baseline, Week 13, 24, 36 and 48
ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Number of CUA lesions were measured by using magnetic resonance imaging (MRI) scans.
Measured: ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96
OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Number of combined unique active (CUA) lesions were measured by using magnetic resonance imaging (MRI) scans.
Measured: OLMP: Baseline, Week 24, 48, 72 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Number of CUA MRI lesions were measured by using magnetic resonance imaging (MRI) scans.
Measured: LTFU: Baseline, Week 13, 24 and 36
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Number of CUA lesions were measured by using magnetic resonance imaging (MRI) scans.
Measured: LTFU: Baseline, Week 13, 24, 36 and 48
ITP: Change From Baseline in Volume of T1 Gd-Enhanced Lesions
Change in volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
Measured: ITP: Baseline, Week 96
OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions
Volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
Measured: OLMP: Baseline, Week 24, 48, 72 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions
Volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
Measured: LTFU: Baseline, Week 13, 24 and 36
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions
Volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
Measured: LTFU: Baseline, Week 13, 24, 36 and 48
ITP: Changes From Baseline in Volume of T2 Lesions
Change in volume of T2 lesions from baseline was measured by using magnetic resonance imaging (MRI) scans.
Measured: ITP: Baseline, Week 48 and 96
OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions
Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans.
Measured: OLMP: Baseline, Week 48 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T2 Lesions
Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans.
Measured: LTFU: Baseline (Day 1)
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions
Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans.
Measured: Baseline, Week 48
ITP: Number of T1 Hypointense Lesions
Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
Measured: ITP: Baseline, Week 48 and 96
OLMP: Number of T1 Hypointense Lesions
Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
Measured: OLMP: Baseline, Week 48 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of T1 Hypointense Lesions
Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
Measured: LTFU: Baseline (Day 1)
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of T1 Hypointense Lesions
Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
Measured: LTFU: Baseline, Week 48
ITP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
Measured: ITP: Baseline up to Week 96
OLMP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
Measured: OLMP: Baseline up to Week 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
Measured: LTFU: Baseline up to Week 48
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
Measured: Baseline up to Week 48
ITP: Percentage of Participants With no New or Enlarging T2 Lesions
T2 lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or enlarging T2 lesions were reported.
Measured: ITP: Baseline up to Week 96
OLMP: Percentage of Participants With no New or Enlarging T2 Lesions
T2 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or enlarging T2 Lesions were reported.
Measured: OLMP: Baseline up to 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions
Enlarging T2 Lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no New or Enlarging T2 Lesions were reported.
Measured: Baseline up to Week 48
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions
Enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no New or Enlarging T2 lesions were reported.
Measured: LTFU: Baseline up to Week 48
ITP: Percent Change From Baseline in Brain Volume
Brain volume was measured by using magnetic resonance imaging (MRI) scans. Percent change from baseline in brain volume at Week 48 and 96 was reported.
Measured: ITP: Baseline, Week 48 and 96
OLMP: Percent Change From Baseline in Brain Volume
Brain volume was measured by using magnetic resonance imaging (MRI) scans. Percent change from baseline in brain volume at Week 48 and 96 was reported.
Measured: OLMP: Baseline, Week 48 and 96
OLMP: Number of Relapses
Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
Measured: Baseline up to Week 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Relapses
Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
Measured: Baseline up to Week 48
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Relapses
Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
Measured: Baseline up to Week 48
OLMP: Annualized Relapse Rate
The annualized relapse rate for each treatment group was the mean of the annualized relapse rates for all the participants in the group, calculated as the total number of confirmed relapses divided by the total number of days on study multiplied by 365.25. Where, Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
Measured: Baseline up to Week 96
OLMP: Percentage of Relapse-Free Participants
Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Percentage of relapse-free participants were reported.
Measured: Baseline up to Week 96
ITP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. SAE: Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious TEAEs and non-serious TEAEs. Number of Participants with TEAEs and serious TEAEs were reported.
Measured: ITP: Baseline up to Week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2008 (estimated)
- Study start31 Dec 2008
- Primary completion31 Jul 2011
- Study completion30 Apr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by EMD Serono Research & Development Institute, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 617 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bettina Stubinski, MD, Study director, Merck Serono S.A., Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00725985
- Sponsor's protocol ID
- 28821
- Acronym
- ORACLE MS
- Status last verified
- Feb 2021
- First submitted
- 30 Jul 2008
- Last updated
- 22 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Oh J, Walker B, Giovannoni G, Jack D, Dangond F, Nolting A, Aldridge J, Lebson LA, Leist TP. Side effects that occurred early in people with multiple sclerosis during the first year of treatment with cladribine tablets: a plain language summary. Neurodegener Dis Manag. 2022 Feb 1;12(1):1-7. doi: 10.2217/nmt-2021-0041. Epub 2022 Jan 12.
PubMed 35019731Giovannoni G, Coyle PK, Vermersch P, Walker B, Aldridge J, Nolting A, Galazka A, Lemieux C, Leist TP. Integrated Lymphopenia Analysis in Younger and Older Patients With Multiple Sclerosis Treated With Cladribine Tablets. Front Immunol. 2021 Dec 24;12:763433. doi: 10.3389/fimmu.2021.763433. eCollection 2021.
PubMed 35003076Giovannoni G, Galazka A, Schick R, Leist T, Comi G, Montalban X, Damian D, Dangond F, Cook S. Pregnancy Outcomes During the Clinical Development Program of Cladribine in Multiple Sclerosis: An Integrated Analysis of Safety. Drug Saf. 2020 Jul;43(7):635-643. doi: 10.1007/s40264-020-00948-x.
PubMed 32447743Freedman MS, Leist TP, Comi G, Cree BA, Coyle PK, Hartung HP, Vermersch P, Damian D, Dangond F. The efficacy of cladribine tablets in CIS patients retrospectively assigned the diagnosis of MS using modern criteria: Results from the ORACLE-MS study. Mult Scler J Exp Transl Clin. 2017 Oct 9;3(4):2055217317732802. doi: 10.1177/2055217317732802. eCollection 2017 Oct-Dec.
PubMed 29051829Leist TP, Comi G, Cree BA, Coyle PK, Freedman MS, Hartung HP, Vermersch P, Casset-Semanaz F, Scaramozza M; oral cladribine for early MS (ORACLE MS) Study Group. Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial. Lancet Neurol. 2014 Mar;13(3):257-67. doi: 10.1016/S1474-4422(14)70005-5. Epub 2014 Feb 4.
PubMed 24502830
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center Clinical Trial of Oral Cladribine in Subjects With a First Clinical Event at High Risk of Converting to MS
- ClinicalTrials.gov ID
- NCT00725985
- Acronym / sponsor ID
- ORACLE MS / 28821
- Conditions
- Multiple Sclerosis
- Keywords
- Clinically Isolated Syndrome (CIS), Early MS, Multiple Sclerosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 617 participants (actual)
- Lead sponsor
- EMD Serono Research & Development Institute, Inc.Industry (pharma, biotech, devices)
- Study start
- 31 Dec 2008 (actual)
- Primary completion
- 31 Jul 2011 (actual)
- Study completion
- 30 Apr 2012 (actual)
- First posted
- 31 Jul 2008 (estimated)
- Results
- Posted 10 Oct 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A randomized, double-blind, clinical trial to assess the safety and efficacy of two doses of oral cladribine versus placebo in participants who had a first clinical demyelinating event (clinically isolated syndrome). Participants in either the cladribine or placebo group may also enter treatment periods with open-label interferon-beta or open-label cladribine depending upon the disease status. The primary objective of this study is to evaluate the effect of two dosage regimens of oral cladribine versus placebo on the time to conversion to multiple sclerosis (MS) (from randomization) according to the Poser criteria in participants with first clinical demyelinating event at high risk of converting to MS.
Detailed description
This will be a randomized, double blind, three-arm, placebo-controlled, multi-center trial to evaluate the safety and efficacy of oral cladribine versus placebo in the treatment of participants who have sustained a first clinical demyelinating event within 75 days prior to the Screening. Participants must have a minimum of 2 clinically silent lesions on the Screening magnetic resonance imaging (MRI).
The study will include a pre-study evaluation period (Screening period: between 10 and 28 days prior to the start of treatment with blinded study medication (oral cladribine or placebo).
Depending upon the clinical course of their MS, participants will then proceed from the ITP to either the Maintenance Treatment Period (with open-label interferon-beta treatment) or LTFU period (with either open-label low-dose cladribine or no additional treatment (if no progression to MS has been noted after the initial treatment period). The single primary endpoint for the overall study, which will be determined during the ITP, is time to conversion to MS (from randomization), according to the Poser criteria.
For every participants, eligibility for study enrollment and entry into each of the study periods, and diagnosis of conversion to either McDonald MS or CDMS must be confirmed and approved by a Sponsor appointed study Adjudication Committee.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | Experimental | Drug: Cladribine, Drug: Rebif® new formulation (RNF)Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 milligrams per kilograms (mg/kg) during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first. |
| Cladribine 3.5 mg/kg (ITP) | Experimental | Drug: Cladribine, Drug: Rebif® new formulation (RNF)Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first. |
| Placebo (ITP) | Placebo comparator | Drug: Placebo, Drug: Rebif® new formulation (RNF)Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first. |
| Cladribine 5.25 mg/kg, Rebif (OLMP) | Experimental | Drug: Cladribine, Drug: Rebif® new formulation (RNF)Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants. |
| Cladribine 3.5 mg/kg, Rebif (OLMP) | Experimental | Drug: Cladribine, Drug: Rebif® new formulation (RNF)Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants. |
| Placebo, Rebif (OLMP) | Experimental | Drug: PlaceboParticipants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants. |
| Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU) | Experimental | Drug: Cladribine, Drug: Rebif® new formulation (RNF)Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU. |
| Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU) | Experimental | Drug: Cladribine, Drug: Rebif® new formulation (RNF)Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU. |
| Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU) | Experimental | Drug: PlaceboParticipants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU. |
| Cladribine 5.25 mg/kg, Rebif (LTFU) | Experimental | Drug: Cladribine, Drug: Rebif® new formulation (RNF)Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU. |
| Cladribine 3.5 mg/kg, Rebif (LTFU) | Experimental | Drug: Cladribine, Drug: Rebif® new formulation (RNF)Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU. |
| Placebo, Rebif (LTFU) | Experimental | Drug: PlaceboParticipants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- Male or female between 18 and 55 years old, inclusive
- Weighed between 40 to 120 kilogram (kg), inclusive
- Participant has experienced a single, first clinical event suggestive of MS within 75 days prior to the Screening visit, (clock starts 24 hours after onset). The event must be a new neurological abnormality present for at least 24 hours, either mono- or polysymptomatic
- Participant has at least two clinically silent lesions on the T2-weighted MRI scan, at screening, with a size of at least 3 millimeter (mm), at least one of which is ovoid or periventricular or infratentorial on screening MRI
- Participant has EDSS 0 - 5.0 at Screening
Key exclusion criteria (23 listed)
- Participant has a diagnosis of MS (per McDonald criteria, 2005)
- Participant has any other disease that could better explain the participant's signs and symptoms
- Participant has complete transverse myelitis or bilateral optic neuritis
- Participant using or has used any other approved MS disease modifying drug (DMD)
- Participant has used any investigational drug or undergone an experimental procedure within 12 weeks prior to Study day 1
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CladribineCladribine tablets were administered until CDMS conversion, whichever occur first. | Drug | Cladribine 3.5 mg/kg (ITP), Cladribine 3.5 mg/kg, Rebif (LTFU), Cladribine 3.5 mg/kg, Rebif (OLMP), Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU), Cladribine 5.25 mg/kg (ITP), Cladribine 5.25 mg/kg, Rebif (LTFU), Cladribine 5.25 mg/kg, Rebif (OLMP), Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU) |
| PlaceboPlacebo matched to cladribine tablets were administered. | Drug | Placebo (ITP), Placebo, Rebif (LTFU), Placebo, Rebif (OLMP), Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU) |
| Rebif® new formulation (RNF)Participants who converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received RNF subcutaneously at a dose of 44 microgram (mcg) three times a week. Participants who converted to CDMS during long-term follow-up (LTFU) period, received RNF subcutaneously at a dose of 44 mcg three times a week. | Drug | Cladribine 3.5 mg/kg (ITP), Cladribine 3.5 mg/kg, Rebif (LTFU), Cladribine 3.5 mg/kg, Rebif (OLMP), Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU), Cladribine 5.25 mg/kg (ITP), Cladribine 5.25 mg/kg, Rebif (LTFU), Cladribine 5.25 mg/kg, Rebif (OLMP), Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU), Placebo (ITP) |
Primary outcome
ITP: Time to Clinically Definite Multiple Sclerosis (CDMS) Conversion Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS
Time frame: ITP: Baseline up to Week 96
CDMS according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to Multiple Sclerosis [MS]) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (>=) 1 point if baseline EDSS was between >= 1.0 and less than or equal to (=<) 4.5; or >= 1.5 points if baseline EDSS was 0, or >= 0.5 if baseline EDSS >= 5.0 over a period of at least 3 months. Kaplan-Meier estimates were provided for of the cumulative (cum.) percentage (%) of participants with CDMS over time. The probability of patients remaining event-free over time (from randomization) in each of the three treatment groups was displayed in the form of survival curves estimated using the non-parametric Kaplan-Meier method.
48 secondary outcomes
ITP: Time to Develop Multiple Sclerosis (MS) Conversion According to the Revised McDonald Criteria (2005) Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With McDonald MS
Time frame: ITP: Baseline up to Week 96
ITP: Number of Combined Unique Active (CUA) Lesions, New or Enlarging Time Constant 2 (T2) Lesions, and New or Persisting Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan
Time frame: ITP: Baseline up to Week 96
OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression
Time frame: OLMP: Day 1, 90, 180, 270, 360, 450, 540, 630, 720 and 810
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Multiple Sclerosis (MS) According to the 2005 McDonald Criteria
Time frame: Time from Randomization up to 1217 days
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria
Time frame: Time from Randomization up to 1217 days
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria
Time frame: Time from Randomization up to 1217 days
ITP: Percentage of Participants Converting to Clinically Definite Multiple Sclerosis (CDMS) as Per Poser Criteria
Time frame: ITP: Baseline up to week 96
ITP: Percentage of Participants Converting to McDonald Multiple Sclerosis (MS) (2005)
Time frame: ITP: Baseline up to week 96
ITP: Number of New or Persisting Gd-enhanced Lesions
Time frame: ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96
OLMP: Number of New or Persisting Gd-enhanced Lesions
Time frame: OLMP: Baseline, Week 24, 48, 72 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions
Time frame: LTFU: Baseline, Week 13, 24 and 36
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions
Time frame: LTFU: Baseline, Week 13, 24, 36 and 48
ITP: Number of New or Enlarging T2 Lesions
Time frame: ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96
OLMP: Number of New or Enlarging T2 Lesions
Time frame: OLMP: Baseline, Week 24, 48, 72 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions
Time frame: LTFU: Baseline, Week 13, 24 and 36
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions
Time frame: LTFU: Baseline, Week 13, 24, 36 and 48
ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Time frame: ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96
OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Time frame: OLMP: Baseline, Week 24, 48, 72 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Time frame: LTFU: Baseline, Week 13, 24 and 36
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Time frame: LTFU: Baseline, Week 13, 24, 36 and 48
ITP: Change From Baseline in Volume of T1 Gd-Enhanced Lesions
Time frame: ITP: Baseline, Week 96
OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions
Time frame: OLMP: Baseline, Week 24, 48, 72 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions
Time frame: LTFU: Baseline, Week 13, 24 and 36
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions
Time frame: LTFU: Baseline, Week 13, 24, 36 and 48
ITP: Changes From Baseline in Volume of T2 Lesions
Time frame: ITP: Baseline, Week 48 and 96
OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions
Time frame: OLMP: Baseline, Week 48 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T2 Lesions
Time frame: LTFU: Baseline (Day 1)
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions
Time frame: Baseline, Week 48
ITP: Number of T1 Hypointense Lesions
Time frame: ITP: Baseline, Week 48 and 96
OLMP: Number of T1 Hypointense Lesions
Time frame: OLMP: Baseline, Week 48 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of T1 Hypointense Lesions
Time frame: LTFU: Baseline (Day 1)
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of T1 Hypointense Lesions
Time frame: LTFU: Baseline, Week 48
ITP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
Time frame: ITP: Baseline up to Week 96
OLMP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
Time frame: OLMP: Baseline up to Week 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
Time frame: LTFU: Baseline up to Week 48
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
Time frame: Baseline up to Week 48
ITP: Percentage of Participants With no New or Enlarging T2 Lesions
Time frame: ITP: Baseline up to Week 96
OLMP: Percentage of Participants With no New or Enlarging T2 Lesions
Time frame: OLMP: Baseline up to 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions
Time frame: Baseline up to Week 48
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions
Time frame: LTFU: Baseline up to Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35019731Oh J, Walker B, Giovannoni G, Jack D, Dangond F, Nolting A, Aldridge J, Lebson LA, Leist TP. Side effects that occurred early in people with multiple sclerosis during the first year of treatment with cladribine tablets: a plain language summary. Neurodegener Dis Manag. 2022 Feb 1;12(1):1-7. doi: 10.2217/nmt-2021-0041. Epub 2022 Jan 12.
- Derived from this study: PubMed 35003076Giovannoni G, Coyle PK, Vermersch P, Walker B, Aldridge J, Nolting A, Galazka A, Lemieux C, Leist TP. Integrated Lymphopenia Analysis in Younger and Older Patients With Multiple Sclerosis Treated With Cladribine Tablets. Front Immunol. 2021 Dec 24;12:763433. doi: 10.3389/fimmu.2021.763433. eCollection 2021.
- Derived from this study: PubMed 32447743Giovannoni G, Galazka A, Schick R, Leist T, Comi G, Montalban X, Damian D, Dangond F, Cook S. Pregnancy Outcomes During the Clinical Development Program of Cladribine in Multiple Sclerosis: An Integrated Analysis of Safety. Drug Saf. 2020 Jul;43(7):635-643. doi: 10.1007/s40264-020-00948-x.
- Derived from this study: PubMed 29051829Freedman MS, Leist TP, Comi G, Cree BA, Coyle PK, Hartung HP, Vermersch P, Damian D, Dangond F. The efficacy of cladribine tablets in CIS patients retrospectively assigned the diagnosis of MS using modern criteria: Results from the ORACLE-MS study. Mult Scler J Exp Transl Clin. 2017 Oct 9;3(4):2055217317732802. doi: 10.1177/2055217317732802. eCollection 2017 Oct-Dec.
- Derived from this study: PubMed 24502830Leist TP, Comi G, Cree BA, Coyle PK, Freedman MS, Hartung HP, Vermersch P, Casset-Semanaz F, Scaramozza M; oral cladribine for early MS (ORACLE MS) Study Group. Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial. Lancet Neurol. 2014 Mar;13(3):257-67. doi: 10.1016/S1474-4422(14)70005-5. Epub 2014 Feb 4.
- Trial Awareness and Transparency websiteLink provided by the sponsor.
- US Medical Information website, Medical ResourcesLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bettina Stubinski, MD study director
Merck Serono S.A., Geneva
158 sites in 34 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cladribine and Rebif® new formulation (RNF) in people with Multiple Sclerosis, run by EMD Serono Research & Development Institute, Inc. at 158 sites in 34 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 158 sites in Russia, United States, Italy, Bulgaria, Poland and 29 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Oct 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ITP: Time to Clinically Definite Multiple Sclerosis (CDMS) Conversion Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS (time frame: ITP: Baseline up to Week 96). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00725985, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2021.