Multiple SclerosisPhase 3REFLEXNCT00404352
REbif FLEXible Dosing in Early Multiple Sclerosis (MS)
A Phase 3 study testing RNF in people with Multiple Sclerosis, run by Merck KGaA, Darmstadt, Germany at 67 sites in 27 countries.
Trial summary
The study is a 24 months randomized, double-blind, Placebo-controlled, multi-center clinical trial with an optional 12 months open label extension. The primary objective of the study is to evaluate the effect of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN] beta-1a (RNF)… Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- RNF
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 517 participants
- Where
- 67 sitesin 27 countries
- Study dates
- Nov 2006to Jul 2011
- 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 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Single, first clinical event suggestive of MS within 60 days prior to study Day 1, which is the day of randomization (clock starts 24 hours after onset). The event must be a new neurological abnormality present for at least 24 hours, either mono- or polysymptomatic, other than a paresthesia, vegetative or cerebral dysfunction
- At least two clinically silent lesions on the T2-weighted MRI scan, with a size of at least 3 millimeter (mm), at least one of which is ovoid or periventricular or infratentorial
- EDSS 0 - 5.0 at least one time point during the screening period before start of treatment
- 18 and 50 years old, inclusive
- Willing to follow study procedures
- Written informed consent
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- If female, subject must:
- be neither pregnant nor breast-feeding nor attempting to conceive
- use a highly effective method of contraception. A highly effective method of contraception is defined as those which result in a low failure rate (that is [i.e.] less than 1 percent [%] per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomised partner
Who cannot join
- Diagnosis of MS (per McDonald criteria 2005)
- Any other disease that could better explain the subject's signs and symptoms
- Complete transverse myelitis or bilateral optic neuritis
- Subject uses or has used any other approved MS disease-modifying drug (DMD)
- Any investigational drug or undergone an experimental procedure within 12 weeks prior to study Day 1
- Oral or systemic corticosteroids or adrenocorticotropic hormone (ACTH) within 30 days prior to study Day 1
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- Total bilirubin greater than 2.5 times upper limit of normal (ULN)
- Subject has total aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or alkaline phosphatase (ALP) greater than 2.5 times the ULN
- Inadequate bone marrow reserve, defined as a total white blood cell count less than 3.0 x 109 per liter (/L), platelet count less than 75 x 109/L, hemoglobin less than 100 gram per liter (g/L)
- Current autoimmune disease
- Major medical or psychiatric illness (including history of or current severe depressive disorders and/or suicidal ideation) that in the opinion of the investigator creates undue risk to the subject or could affect compliance with the study protocol
- History of seizures not adequately controlled by treatment
- Cardiac disease, such as angina, congestive heart failure or arrhythmia
- Known allergy to IFN-beta or the excipient(s) of the study medication
- Any condition that could interfere with the MRI evaluation;
- Known allergy to gadolinium-diethylene triamine pentaacetic acid (DTPA)
- Previously participated in this study
- Participated in any clinical trial within the past 6 months
- Any immunomodulatory or immunosuppressive therapy at any time prior to enrollment, including, but not limited to, the following products: any IFN, glatiramer acetate (Copolymer I), cyclophosphamide, cyclosporine, methotrexate, linomide, azathioprine, mitoxantrone, teriflunomide, laquinimod, cladribine, total lymphoid irradiation, anti-lymphocyte monoclonal antibody treatment (e.g. natalizumab, alemtuzumab/Campath, anti-cluster of differentiation 4 [CD4]), intravenous, immunoglobulins (Igs), cytokines or anti-cytokine therapy
- Any experimental MS treatment prior to trial entry, including, but not limited to, any statins (if given to prevent MS) and pentoxyfylline
- History of alcohol or drug abuse
- Intolerance or any contraindication to both paracetamol (acetaminophen) and ibuprofen
- Inability to administer subcutaneous injections either by self or by caregiver
- Moderate to severe renal impairment
Trial locations and contacts
67 sites in 27 countries.
67 sites in 27 countries
Russia7 sites
Research Site
Moscow
Research Site
Nizhny Novgorod
Research Site
Novosibirsk
Research Site
Saint Petersburg
Research Site
Samara
Research Site
Saratov
Research Site
Yekaterinburg
Bulgaria5 sites
Research Site
Pleven
Research Site
Rousse
Research Site
Shumen
Research Site
Sofia
Research Site
Varna
Croatia5 sites
Research Site
Karlovac
Research Site
Osijek
Research Site
Rijeka
Research Site
Split
Research Site
Zagreb
Italy4 sites
Research Site
Catania
Research Site
Milan
Research Site
Padova
Research Site
Roma
Poland4 sites
Research Site
Bialystok
Research Site
Lodz
Research Site
Warsaw
Research Site
Wroclaw
Romania4 sites
Research Site
Bucharest
Research Site
Iași
Research Site
Târgu Mureş
Research Site
Timișoara
Spain4 sites
Research Site
Barcelona
Research Site
Bilbao
Research Site
Madrid
Research Site
Seville
Canada3 sites
Research Site
Montreal, Quebec
Research Site
Ontario
Research Site
Victoria British Columbia
Czechia3 sites
Research Site
Hradec Králové
Research Site
Olomouc
Research Site
Prague
Germany3 sites
Research Site
Hanover
Research Site
Henningsdorf
Research Site
Munich
Israel3 sites
Research Site
Ness Ziona
Research Site
Safed
Research Site
Tel Litwinsky
About this study
Official title: A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Trial of Rebif New Formulation (44 Microgram [Mcg] Three Times Weekly [Tiw] and 44 Mcg Once Weekly [ow]) in Subjects at High Risk of Converting to Multiple Sclerosis (REFLEX)
The study is a 24 months randomized, double-blind, Placebo-controlled, multi-center clinical trial with an optional 12 months open label extension.
The primary objective of the study is to evaluate the effect of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN] beta-1a (RNF) 44 microgram (three times weekly and once weekly) versus placebo on the time to conversion to McDonald multiple sclerosis (MS) criteria (2005) in subjects with a first clinical demyelinating event at high risk of converting to MS.
Read more
The main secondary objective of study is to evaluate the effect of RNF 44 microgram (three times weekly and once weekly) versus placebo on the "Time to conversion to clinically definite MS (CDMS)" in subjects with a first clinical demyelinating event at high risk of converting to MS.
At the end of 24 month double-blind core REFLEX trial, subjects who will not convert to CDMS and decide to receive open-label (OL) treatment will be enrolled into an open-label, 12 month extension period to evaluate the effect of RNF 44 mcg three times weekly treatment on the time to conversion to McDonald MS and time to conversion to CDMS.
- Conditions
- Multiple Sclerosis
- Being tested
- RNF, Placebo
- Keywords
- Rebif New Formulation, Clinical Isolated Syndrome, 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.
RNFDrug
Also called Rebif
Single dose of RNF administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months, or 36 months for patients enrolled in the OL extension.
RNFDrug
Also called Rebif
Single dose of RNF administered subcutaneously once weekly at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months.
PlaceboDrug
Placebo was supplied as a transparent, sterile solution for injection in pre-filled syringes matching the RNF pre-filled syringes, each containing 0.5 mL.
| Study group | Role | What they receive |
|---|---|---|
| RNF 44 mcg three times weekly | Active comparator | Not described Receives: Drug: RNF |
| RNF 44 mcg once weekly and placebo twice weekly for blinding | Active comparator | Not described Receives: Drug: RNF; Drug: Placebo |
| Placebo three times weekly | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Conversion to Multiple Sclerosis (MS) According to the McDonald Criteria (2005)
The McDonald criteria use dissemination in time and space established by magnetic resonance image (MRI) findings to provide a clinical diagnosis for MS. Dissemination in time is established by a new time constant 2 (T2) or gadolinium-enhancing (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.
Measured: Various time points from randomization up to 24 months
Time to Conversion to Multiple Sclerosis (MS) According to the McDonald Criteria (2005)
The McDonald criteria use dissemination in time and space established by MRI findings to provide a clinical diagnosis for MS. Dissemination in time is established by a T2 or 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.
Measured: Various time points from randomization up to 36 months
Secondary outcomes (5)
Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) Defined by Either a Second Attack or a 3-Month Sustained Increase (Greater Than or Equal to 1.5 Points) in the Expanded Disability Status Scale (EDSS) Score
CDMS was defined by the occurrence of a second exacerbation or relapse over 24 months in participants who presented with first clinical demyelinating event (FCDE) accompanied by an abnormal MRI scan. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated.
Measured: Various time points from randomization up to 24 months
Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) Defined by Either a Second Attack or a 3-Month Sustained Increase (Greater Than or Equal to 1.5 Points) in the Expanded Disability Status Scale (EDSS) Score
CDMS was defined by the occurrence of a second exacerbation or relapse over 36 months in participants who presented with FCDE accompanied by an abnormal MRI scan. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated.
Measured: Various time points from randomization up to 36 months
Mean Number of Combined Unique Active (CUA) Lesions, New Time Constant 2 (T2) Lesions, Gadolinium Enhanced (Gd+) Lesions and New Time Constant 1 (T1) Hypointense Lesions Per Participant Per Scan
Number of CUA lesions, new T2 lesions, Gd+ lesions and new T1 hypointense lesions were measured by using MRI scans.
Measured: Month 24 up to Month 36
Change From Baseline in Time Constant 2 (T2) Lesion Volume , Time Constant 1 (T1) Hypointense Lesion Volume and Gadolinium Enhanced (Gd+) Lesion Volume at Month 36
Change from baseline in lesion volume was measured by using MRI scans for T2 lesions, T1 hypointense lesions and (Gd+) lesions.
Measured: Baseline, Month 36
Change From Baseline in Expanded Disability Status Score (EDSS) Score at Month 36
EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. The change in EDSS at Month 36 was calculated as EDSS at Month 36 minus EDSS at baseline.
Measured: Baseline, Month 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2006 (estimated)
- Study startNov 2006
- Primary completionAug 2010
- Study completionJul 2011
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.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 517 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bettina M. Stubinski, MD, Study director, Merck Serono S.A., Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00404352
- Sponsor's protocol ID
- IMP27025
- Other IDs
- 2006-002982-38
- Acronym
- REFLEX
- Status last verified
- Dec 2013
- First submitted
- 27 Nov 2006
- Last updated
- 24 Jan 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kuhle J, Leppert D, Comi G, de Stefano N, Kappos L, Freedman MS, Seitzinger A, Roy S. Serum neurofilament light chain correlations in patients with a first clinical demyelinating event in the REFLEX study: a post hoc analysis. Ther Adv Neurol Disord. 2024 Mar 29;17:17562864241239101. doi: 10.1177/17562864241239101. eCollection 2024.
PubMed 38560407Battaglini M, Vrenken H, Tappa Brocci R, Gentile G, Luchetti L, Versteeg A, Freedman MS, Uitdehaag BMJ, Kappos L, Comi G, Seitzinger A, Jack D, Sormani MP, Barkhof F, De Stefano N. Evolution from a first clinical demyelinating event to multiple sclerosis in the REFLEX trial: Regional susceptibility in the conversion to multiple sclerosis at disease onset and its amenability to subcutaneous interferon beta-1a. Eur J Neurol. 2022 Jul;29(7):2024-2035. doi: 10.1111/ene.15314. Epub 2022 Apr 4.
PubMed 35274413Freedman MS, De Stefano N, Barkhof F, Polman CH, Comi G, Uitdehaag BM, Casset-Semanaz F, Hennessy B, Lehr L, Stubinski B, Jack DL, Kappos L. Patient subgroup analyses of the treatment effect of subcutaneous interferon beta-1a on development of multiple sclerosis in the randomized controlled REFLEX study. J Neurol. 2014 Mar;261(3):490-9. doi: 10.1007/s00415-013-7222-6. Epub 2014 Jan 12.
PubMed 24413638De Stefano N, Comi G, Kappos L, Freedman MS, Polman CH, Uitdehaag BM, Hennessy B, Casset-Semanaz F, Lehr L, Stubinski B, Jack DL, Barkhof F. Efficacy of subcutaneous interferon beta-1a on MRI outcomes in a randomised controlled trial of patients with clinically isolated syndromes. J Neurol Neurosurg Psychiatry. 2014 Jun;85(6):647-53. doi: 10.1136/jnnp-2013-306289. Epub 2013 Nov 29.
PubMed 24292999Comi G, De Stefano N, Freedman MS, Barkhof F, Polman CH, Uitdehaag BM, Casset-Semanaz F, Hennessy B, Moraga MS, Rocak S, Stubinski B, Kappos L. Comparison of two dosing frequencies of subcutaneous interferon beta-1a in patients with a first clinical demyelinating event suggestive of multiple sclerosis (REFLEX): a phase 3 randomised controlled trial. Lancet Neurol. 2012 Jan;11(1):33-41. doi: 10.1016/S1474-4422(11)70262-9. Epub 2011 Dec 4.
PubMed 22146409
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Trial of Rebif New Formulation (44 Microgram [Mcg] Three Times Weekly [Tiw] and 44 Mcg Once Weekly [ow]) in Subjects at High Risk of Converting to Multiple Sclerosis (REFLEX)
- ClinicalTrials.gov ID
- NCT00404352
- Acronym / sponsor ID
- REFLEX / IMP27025
- Conditions
- Multiple Sclerosis
- Keywords
- Rebif New Formulation, Clinical Isolated Syndrome, Multiple Sclerosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 517 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- Nov 2006
- Primary completion
- Aug 2010 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 28 Nov 2006 (estimated)
- Results
- Posted 24 Sep 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is a 24 months randomized, double-blind, Placebo-controlled, multi-center clinical trial with an optional 12 months open label extension.
The primary objective of the study is to evaluate the effect of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN] beta-1a (RNF) 44 microgram (three times weekly and once weekly) versus placebo on the time to conversion to McDonald multiple sclerosis (MS) criteria (2005) in subjects with a first clinical demyelinating event at high risk of converting to MS.
The main secondary objective of study is to evaluate the effect of RNF 44 microgram (three times weekly and once weekly) versus placebo on the "Time to conversion to clinically definite MS (CDMS)" in subjects with a first clinical demyelinating event at high risk of converting to MS.
At the end of 24 month double-blind core REFLEX trial, subjects who will not convert to CDMS and decide to receive open-label (OL) treatment will be enrolled into an open-label, 12 month extension period to evaluate the effect of RNF 44 mcg three times weekly treatment on the time to conversion to McDonald MS and time to conversion to CDMS.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| RNF 44 mcg three times weekly | Active comparator | Drug: RNF |
| RNF 44 mcg once weekly and placebo twice weekly for blinding | Active comparator | Drug: RNF, Drug: Placebo |
| Placebo three times weekly | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Single, first clinical event suggestive of MS within 60 days prior to study Day 1, which is the day of randomization (clock starts 24 hours after onset). The event must be a new neurological abnormality present for at least 24 hours, either mono- or polysymptomatic, other than a paresthesia, vegetative or cerebral dysfunction
- At least two clinically silent lesions on the T2-weighted MRI scan, with a size of at least 3 millimeter (mm), at least one of which is ovoid or periventricular or infratentorial
- EDSS 0 - 5.0 at least one time point during the screening period before start of treatment
- 18 and 50 years old, inclusive
- Willing to follow study procedures
Key exclusion criteria (24 listed)
- Diagnosis of MS (per McDonald criteria 2005)
- Any other disease that could better explain the subject's signs and symptoms
- Complete transverse myelitis or bilateral optic neuritis
- Subject uses or has used any other approved MS disease-modifying drug (DMD)
- 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 |
|---|---|---|
| RNFAlso: RebifSingle dose of RNF administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months, or 36 months for patients enrolled in the OL extension. | Drug | RNF 44 mcg once weekly and placebo twice weekly for blinding, RNF 44 mcg three times weekly |
| RNFAlso: RebifSingle dose of RNF administered subcutaneously once weekly at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months. | Drug | RNF 44 mcg once weekly and placebo twice weekly for blinding, RNF 44 mcg three times weekly |
| PlaceboPlacebo was supplied as a transparent, sterile solution for injection in pre-filled syringes matching the RNF pre-filled syringes, each containing 0.5 mL. | Drug | Placebo three times weekly, RNF 44 mcg once weekly and placebo twice weekly for blinding |
Primary outcome
Time to Conversion to Multiple Sclerosis (MS) According to the McDonald Criteria (2005)
Time frame: Various time points from randomization up to 24 months
The McDonald criteria use dissemination in time and space established by magnetic resonance image (MRI) findings to provide a clinical diagnosis for MS. Dissemination in time is established by a new time constant 2 (T2) or gadolinium-enhancing (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.
Time to Conversion to Multiple Sclerosis (MS) According to the McDonald Criteria (2005)
Time frame: Various time points from randomization up to 36 months
The McDonald criteria use dissemination in time and space established by MRI findings to provide a clinical diagnosis for MS. Dissemination in time is established by a T2 or 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.
5 secondary outcomes
Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) Defined by Either a Second Attack or a 3-Month Sustained Increase (Greater Than or Equal to 1.5 Points) in the Expanded Disability Status Scale (EDSS) Score
Time frame: Various time points from randomization up to 24 months
Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) Defined by Either a Second Attack or a 3-Month Sustained Increase (Greater Than or Equal to 1.5 Points) in the Expanded Disability Status Scale (EDSS) Score
Time frame: Various time points from randomization up to 36 months
Mean Number of Combined Unique Active (CUA) Lesions, New Time Constant 2 (T2) Lesions, Gadolinium Enhanced (Gd+) Lesions and New Time Constant 1 (T1) Hypointense Lesions Per Participant Per Scan
Time frame: Month 24 up to Month 36
Change From Baseline in Time Constant 2 (T2) Lesion Volume , Time Constant 1 (T1) Hypointense Lesion Volume and Gadolinium Enhanced (Gd+) Lesion Volume at Month 36
Time frame: Baseline, Month 36
Change From Baseline in Expanded Disability Status Score (EDSS) Score at Month 36
Time frame: Baseline, Month 36
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38560407Kuhle J, Leppert D, Comi G, de Stefano N, Kappos L, Freedman MS, Seitzinger A, Roy S. Serum neurofilament light chain correlations in patients with a first clinical demyelinating event in the REFLEX study: a post hoc analysis. Ther Adv Neurol Disord. 2024 Mar 29;17:17562864241239101. doi: 10.1177/17562864241239101. eCollection 2024.
- Derived from this study: PubMed 35274413Battaglini M, Vrenken H, Tappa Brocci R, Gentile G, Luchetti L, Versteeg A, Freedman MS, Uitdehaag BMJ, Kappos L, Comi G, Seitzinger A, Jack D, Sormani MP, Barkhof F, De Stefano N. Evolution from a first clinical demyelinating event to multiple sclerosis in the REFLEX trial: Regional susceptibility in the conversion to multiple sclerosis at disease onset and its amenability to subcutaneous interferon beta-1a. Eur J Neurol. 2022 Jul;29(7):2024-2035. doi: 10.1111/ene.15314. Epub 2022 Apr 4.
- Derived from this study: PubMed 24413638Freedman MS, De Stefano N, Barkhof F, Polman CH, Comi G, Uitdehaag BM, Casset-Semanaz F, Hennessy B, Lehr L, Stubinski B, Jack DL, Kappos L. Patient subgroup analyses of the treatment effect of subcutaneous interferon beta-1a on development of multiple sclerosis in the randomized controlled REFLEX study. J Neurol. 2014 Mar;261(3):490-9. doi: 10.1007/s00415-013-7222-6. Epub 2014 Jan 12.
- Derived from this study: PubMed 24292999De Stefano N, Comi G, Kappos L, Freedman MS, Polman CH, Uitdehaag BM, Hennessy B, Casset-Semanaz F, Lehr L, Stubinski B, Jack DL, Barkhof F. Efficacy of subcutaneous interferon beta-1a on MRI outcomes in a randomised controlled trial of patients with clinically isolated syndromes. J Neurol Neurosurg Psychiatry. 2014 Jun;85(6):647-53. doi: 10.1136/jnnp-2013-306289. Epub 2013 Nov 29.
- Derived from this study: PubMed 22146409Comi G, De Stefano N, Freedman MS, Barkhof F, Polman CH, Uitdehaag BM, Casset-Semanaz F, Hennessy B, Moraga MS, Rocak S, Stubinski B, Kappos L. Comparison of two dosing frequencies of subcutaneous interferon beta-1a in patients with a first clinical demyelinating event suggestive of multiple sclerosis (REFLEX): a phase 3 randomised controlled trial. Lancet Neurol. 2012 Jan;11(1):33-41. doi: 10.1016/S1474-4422(11)70262-9. Epub 2011 Dec 4.
- Full FDA approved prescribing information can be found hereLink 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 M. Stubinski, MD study director
Merck Serono S.A., Geneva
67 sites in 27 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing RNF in people with Multiple Sclerosis, run by Merck KGaA, Darmstadt, Germany at 67 sites in 27 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 9 inclusion and 24 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 24 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 67 sites in Russia, Bulgaria, Croatia, Italy, Poland and 22 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 24 Sep 2012). 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?
Time to Conversion to Multiple Sclerosis (MS) According to the McDonald Criteria (2005) (time frame: Various time points from randomization up to 24 months). The study lists 2 primary outcomes in all. 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 NCT00404352, 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 24 Jan 2014.