Relapsing Multiple SclerosisPhase 2ATAMS extNCT00853762
Atacicept in Multiple Sclerosis Extension Study, Phase II
A Phase 2 study testing Atacicept 25 mg, Atacicept 75 mg and Atacicept 150 mg in people with Relapsing Multiple Sclerosis, run by EMD Serono at 47 sites in 17 countries.
Trial summary
This study (28851) is a long-term follow-up study of subjects enrolled in ATAMS study 28063 (NCT00642902). The aim of this study is to monitor the safety and tolerability of atacicept administered for up to 5 years to subjects with relapsing multiple sclerosis (RMS). This extension study consists of two parts. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Relapsing Multiple Sclerosis
- What is being tested?
- Atacicept 25 mg, Atacicept 75 mg and Atacicept 150 mg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 47 sitesin 17 countries
- Study dates
- Mar 2009to Feb 2011
- Phase
- Phase 2
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Participation in study 28063.
- Completion of Week 36 visit of the core study 28063.
- Willingness and ability to comply with study procedures for the duration of the study.
- Voluntary provision of written informed consent (including, for the USA, subject authorization under the Health Insurance Portability and Accountability Act (HIPAA)), given before any study-related procedure that is not part of normal medical care and with the understanding that the subject may withdraw consent at any time without prejudice to his or her future medical care.
Who cannot join
- Premature discontinuation of core study 28063.
- Subjects who meet criteria listed below will receive IMP in study 28851:
- Subjects who are eligible for participation in extension study 28851 but do not meet these criteria will not be treated with IMP but will undergo scheduled visits, irrespective of their treatment.
- All subjects must satisfy the following criteria before Extension Study Day 1 (D1-EXT; defined as the first day of dosing in the extension study) to be eligible for treatment with IMP:
- Eligibility for participation in extension study 28851.
- For women of childbearing potential, a negative urine pregnancy test at eligibility assessment.
Show all 24Show fewer
- Female subjects of childbearing potential must be willing to avoid pregnancy by using an adequate method of contraception for four (4) weeks before the first dose administered within the extension study, during the study and for twelve (12) weeks after the last dose of trial medication. Adequate contraception is defined as two barrier methods, or one barrier method with spermicide, or an intrauterine device, or use of a combined oral female hormonal contraceptive (or the definitions requested by health authorities and locally amended in the core study 28063). For the purposes of this trial, women of childbearing potential are defined as: "All female subjects after puberty unless they are post-menopausal for at least two years or are surgically sterile" (For Germany Only: Female subjects of childbearing potential must be willing to avoid pregnancy by using highly effective methods of contraception for approximately four (4) weeks prior to D1-EXT, during and for twelve (12) weeks after the last dose of trial medication. This requirement does not apply to surgically sterile subjects or to subjects who are postmenopausal for at least 2 years. Highly effective contraception is defined as any method or combination of methods which result in a low failure rate (i.e. less than (<) 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, sexual abstinence, vasectomized partner, 2 barrier methods, or 1 barrier method with spermicide)
- Willingness and ability to comply with study procedures for the duration of the study.
- To be eligible for treatment with investigational medicinal product (IMP) in study 28851, the subjects must not meet any of the following criteria:
- Non-eligibility for participation in extension study 28851 (premature discontinuation of core study 28063).
- Major protocol violation or non-compliance in the core study.
- Use of prohibited immunomodulatory / immunosuppressive therapies
- Serum immunoglobulin G (IgG) level <3 gram per liter (g/L) if the subject received atacicept in the core study, or serum IgG level <6 g/L if the subject received placebo in the core study (to protect the blinding of the core study, the IgG level will be communicated to the treating physician only if it is too low for extension study participation and only after all Week 36 assessments performed within the core study have been completed).
- Any condition, including laboratory findings that, in the opinion of the Investigator, constitutes a risk or a contraindication for participation in the extension study, or that could interfere with the study objectives, conduct or evaluation.
- Known active clinically significant acute or chronic infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives.
- Investigator judgement that treatment of the subject with atacicept in the extension study is not appropriate.
- Aspartate aminotransferase (AST), or alanine aminotransferase (ALT), or alkaline phosphatase (AP) level greater than (>)2.5 x upper limit of normal (ULN), or total bilirubin >1.5 x ULN at eligibility assessment.
- Clinically significant abnormality in any hematological test (e.g. hemoglobin <100 g/L (6.21 millimoles per liter [mmol/L]), white blood cells <3 x 10^9 per liter (/L), platelets <100 x 10^9/L) at eligibility assessment.
- Clinically significant abnormality on electrocardiogram (ECG) performed at eligibility assessment.
- Presence of uncontrolled or New York Health Association (NYHA) class 3 or 4 congestive heart failure at Week 36 of the core study.
- Moderate to severe renal impairment (creatinine clearance <50 milliliter per minute (mL/min) according to Cockcroft-Gault equation).
- Allergy or hypersensitivity to gadolinium (Gd).
- Allergy or hypersensitivity to atacicept or to any of the components of the formulated atacicept.
- Diagnosis or family history of Creutzfeldt-Jakob disease (CJD).
Trial locations and contacts
47 sites in 17 countries.
47 sites in 17 countries
Russia7 sites
Research Site
Moscow
Research Site
Novosibirsk
Research Site
Saint Petersburg
Research Site
Samara
Research Site
Vladimir
Research Site
Yaroslavl
Research Site
Yekaterinburg
United States6 sites
Research Site
Cleveland, Ohio
Research Site
East Lansing, Michigan
Research Site
Nashville, Tennessee
Research Site
Northbrook, Illinois
Research Site
Philadelphia, Pennsylvania
Research Site
Phoenix, Arizona
Australia4 sites
Research Site
Box Hill VIC
Research Site
Fitzroy
Research Site
New Lambton
Research Site
Woodville
Ukraine4 sites
Research Site
Kharkiv
Research Site
Kyiv
Research Site
Odesa
Research Site
Uzhhorod
Netherlands3 sites
Research Site
Breda
Research Site
Nieuwegein
Research Site
Rotterdam
Switzerland3 sites
Research Site
Basel
Research Site
Innsbruck
Research Site
Zurich
United Kingdom3 sites
Research Site
London
Research Site
Sheffield
Research Site
Stoke-on-Trent
New Caledonia1 site
Research Site
Winston Salem
About this study
Official title: An Open-label, Multicenter Phase II Extension of Study 28063 (ATAMS) to Obtain Long-term Follow-up Data in Subjects With Relapsing Multiple Sclerosis Treated With Atacicept for up to 5 Years (ATAMS-Extension)
This study (28851) is a long-term follow-up study of subjects enrolled in ATAMS study 28063 (NCT00642902). The aim of this study is to monitor the safety and tolerability of atacicept administered for up to 5 years to subjects with relapsing multiple sclerosis (RMS).
This extension study consists of two parts. Part A will be double blind and Part B will be open label. During Part A, subjects initially randomized to atacicept will continue to receive the atacicept dose to which they have been randomized in study 28063 (ATAMS) once a week subcutaneously (under the skin). Subjects randomized to placebo in ATAMS will receive atacicept at 150 mg once a week subcutaneously during Part A. Once the results of ATAMS are available and the atacicept dose with the best benefit / risk ratio has been identified, all subjects will be switched to this dose and will continue the extension study open-label (Part B). Throughout the study, subjects and investigators will remain blinded with respect to initial and part A treatment allocation/dose.
- Conditions
- Relapsing Multiple Sclerosis
- Being tested
- Atacicept 25 mg, Atacicept 75 mg, Atacicept 150 mg
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atacicept 25 mgDrug
Subjects who received atacicept 25 milligram (mg) subcutaneously (SC) as loading dose twice weekly for first 4 weeks, followed by atacicept 25 mg SC for 32 weeks, in 28063 study will continue with atacicept 25 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.
Atacicept 75 mgDrug
Subjects who received atacicept 75 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 75 mg SC for 32 weeks, in 28063 study will continued with atacicept 75 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.
Atacicept 150 mgDrug
Subjects who received atacicept 150 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 150 mg SC for 32 weeks, in 28063 study will continue with atacicept 150 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.
Atacicept 150 mgDrug
Subjects who received placebo SC twice weekly for first 4 weeks, followed by placebo SC for 32 weeks, in 28063 study will continue with atacicept 150 mg (without loading dose) SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.
| Study group | Role | What they receive |
|---|---|---|
| Atacicept 25 mg (With Loading) | Experimental | Not described Receives: Drug: Atacicept 25 mg |
| Atacicept 75 mg (With Loading) | Experimental | Not described Receives: Drug: Atacicept 75 mg |
| Atacicept 150 mg (With Loading) | Experimental | Not described Receives: Drug: Atacicept 150 mg |
| Atacicept 150 mg (Without Loading) | Experimental | Not described Receives: Drug: Atacicept 150 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity
TEAEs were defined as AEs with a start date after or on the date of the first DB treatment injection in ATAMS Extension and that occurred anytime after treatment discontinuation, or up to the day before first Rebif® rescue medication injection in ATAMS Extension. A serious TEAE was an AE that resulted in any of the following: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAE severity was graded as per Qualitative Toxicity Scale. Local injection site reactions (injection site: pain, redness, itching and swelling) throughout ATAMS Extension, starting after the first trial medication administration. If the subject experienced 1 or more of the above injection site symptoms, these were reported with the AE verbatim term "injection site reaction". For all randomized subjects, there was an option of rescue treatment with Rebif® for 1 year beginning with the first injection of Rebif®).
Measured: From the first dose of study drug administration up to Week 24
Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Blood pressure (systolic and diastolic) was measured after at least 3 minutes resting, with the subject in the seated position.
Measured: Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36
Change From Baseline in Vital Signs: Pulse Rate
Measured: Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36
Change From Baseline in Vital Signs: Temperature
Measured: Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36
Change From Baseline in Electrocardiogram (ECGs)
Measured: Baseline, Week 12 and 36
Number of Subjects With Worsened Post Baseline Shift in Immunoglobulin A (IgA), IgG and IgM Levels
Number of subjects with shifts from normal Grade (Grade 0) at Baseline to worse value at post-baseline (Grade 1 to Grade 4) according to the following criteria: IgA Grade 0: greater than or equal to (>=) lower limit normal (LLN) 0.7 gram per liter (g/L); Grade 1: less than (<) LLN - 0.5 g/L, Grade 2: <0.5g/L -0.3 g/L, Grade 3: <0.3 g/L -0.1 g/L, Grade 4: < 0.1 g/L; IgG Grade 0: >= LLN (7 g/L), Grade 1: < LLN - 5 g/L, Grade 2: <5g/L -4 g/L, Grade 3: <4 g/L -3 g/L and Grade 4: < 3 g/L; IgM Grade 0: >= LLN (0.4 g/L), Grade 1: < LLN - 0.3 g/L, Grade 2: <0.3 g/L -0.2 g/L, Grade 3: <0.2 g/L -0.1 g/L, and Grade 4: < 0.1 g/L are presented in this outcome measure.
Measured: Baseline up to Week 36
Number of Subjects With Positive Neutralizing Antibody (NAb)
Measured: Baseline, Week 12 and 36
Secondary outcomes (8)
Number of Subjects With Clinical Attacks/Relapses
A clinical attack/relapse was defined as the fulfillment of all the following criteria:
- Neurological abnormality, either newly appearing or re-appearing, with abnormality specified by both i) neurological abnormality separated by at least 30 days from onset of a preceding clinical event, and ii) neurological abnormality lasting for at least 24 hours.
- Absence of fever or known infection (fever with temperature (axillary, orally, or intra-auriculary) > 37.5°C/99.5 °Fahrenheit).
- Objective neurological impairment, correlating with the subject's reported symptoms, defined as either i) increase in at least 1 of the functional systems of the Expanded Disability Status Scale (EDSS), or ii) increase of the total EDSS score. EDSS overall score ranging from 0 (normal) to 10 (death due to MS) was calculated.
Measured: Baseline up to Week 24
Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Week 12
EDSS is an ordinal scale in half-point increments that qualifies disability in participants with multiple sclerosis (MS). It assesses the 8 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder, cerebral and other) as well as ambulation. EDSS overall score ranging from 0 (normal) to 10 (death due to MS) was calculated.
Measured: Baseline, Week 12
Change in Multiple Sclerosis Functional Composite (MSFC) Score at Week 12
The MSFC is a multidimensional clinical outcome measure which consists of three sub-tests; Timed 25-Foot Walk, 9-Hole Peg Test and Paced Auditory Serial Addition Test-3(PASAT-3). The Timed 25-Foot Walk is a quantitative measure of lower extremity function. The 9-Hole Peg Test is a quantitative measure of upper extremity (arm and hand) function. The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Standardized results (Z-scores) of these sub-tests and the overall MSFC Z-score as an average of these three Z-scores was calculated. Higher Z-scores reflect better neurological function and a positive change from baseline indicates improvement. An increase in score indicates an improvement (range -3 to +3).
Measured: Week 12
Magnetic Resonance Imaging (MRI) Parameters: Number of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject
Measured: Baseline, Week 12 and 24
Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions (New or Enlarging T2 Lesions) Per Subject
Measured: Baseline, Week 12 and Week 24
Concentrations of Free and Total Atacicept
Measured: Baseline and Week 12
Free B-Lymphocyte Stimulator (BLyS) and Free A Proliferation-Inducing Ligand (APRIL) Serum Concentrations.
Levels of free APRIL and free BLyS: Free APRIL serum samples were to be analyzed by using a validated enzyme-linked immunosorbent assay (ELISA) with limits of detection of 0.3125 nanogram per milliliter (ng/mL) for free APRIL and free BlyS serum samples were analysed using a validated ELISA with limits of detection of 1.56 ng/mL.
Measured: Baseline, Week 12 and 36
Pharmacogenetics/Pharmacogenomics Analysis
Gene expression profiling and gene polymorphism identification were to be used to identify putative markers for response to treatment.
- Genome-wide gene polymorphism characterization by genome-wide scan.
- Targeted gene polymorphism identification of B-Lymphocyte Stimulator (BLyS) , APRIL, (receptor for B cell activating factor of the tumor necrosis factor [TNF] family) BAFF-R, (Transmembrane Activator) TACI and (B Cell Maturation Antigen) BCMA and HLA-DRB1 by direct genotyping or sequencing .
Measured: Day 1 and Week 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2009 (estimated)
- Study startMar 2009
- Primary completionSep 2009
- Study completionFeb 2011
Why it stopped: EMD Serono voluntarily decided to terminate this trial after observing increased MS disease activity in trial 28063 ATAMS \[Please refer to ATAMS\]
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 (1)Papers the sponsor has linked to this study.
- Other trials for Relapsing 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- EMD Serono
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Responsible party
- Sponsor
- Investigators
- Daniel Mikol, MD, PhD, Study director, EMD Serono
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00853762
- Sponsor's protocol ID
- 28851
- Acronym
- ATAMS ext
- Status last verified
- Feb 2017
- First submitted
- 26 Feb 2009
- Last updated
- 20 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kappos L, Hartung HP, Freedman MS, Boyko A, Radu EW, Mikol DD, Lamarine M, Hyvert Y, Freudensprung U, Plitz T, van Beek J; ATAMS Study Group. Atacicept in multiple sclerosis (ATAMS): a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Neurol. 2014 Apr;13(4):353-63. doi: 10.1016/S1474-4422(14)70028-6. Epub 2014 Mar 6.
PubMed 24613349
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multicenter Phase II Extension of Study 28063 (ATAMS) to Obtain Long-term Follow-up Data in Subjects With Relapsing Multiple Sclerosis Treated With Atacicept for up to 5 Years (ATAMS-Extension)
- ClinicalTrials.gov ID
- NCT00853762
- Acronym / sponsor ID
- ATAMS ext / 28851
- Conditions
- Relapsing Multiple Sclerosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: EMD Serono voluntarily decided to terminate this trial after observing increased MS disease activity in trial 28063 ATAMS \[Please refer to ATAMS\]
- Enrolment
- 74 participants (actual)
- Lead sponsor
- EMD SeronoIndustry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Study start
- Mar 2009
- Primary completion
- Sep 2009 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 2 Mar 2009 (estimated)
- Results
- Posted 24 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study (28851) is a long-term follow-up study of subjects enrolled in ATAMS study 28063 (NCT00642902). The aim of this study is to monitor the safety and tolerability of atacicept administered for up to 5 years to subjects with relapsing multiple sclerosis (RMS).
This extension study consists of two parts. Part A will be double blind and Part B will be open label. During Part A, subjects initially randomized to atacicept will continue to receive the atacicept dose to which they have been randomized in study 28063 (ATAMS) once a week subcutaneously (under the skin). Subjects randomized to placebo in ATAMS will receive atacicept at 150 mg once a week subcutaneously during Part A. Once the results of ATAMS are available and the atacicept dose with the best benefit / risk ratio has been identified, all subjects will be switched to this dose and will continue the extension study open-label (Part B). Throughout the study, subjects and investigators will remain blinded with respect to initial and part A treatment allocation/dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Atacicept 25 mg (With Loading) | Experimental | Drug: Atacicept 25 mg |
| Atacicept 75 mg (With Loading) | Experimental | Drug: Atacicept 75 mg |
| Atacicept 150 mg (With Loading) | Experimental | Drug: Atacicept 150 mg |
| Atacicept 150 mg (Without Loading) | Experimental | Drug: Atacicept 150 mg |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Participation in study 28063.
- Completion of Week 36 visit of the core study 28063.
- Willingness and ability to comply with study procedures for the duration of the study.
- Voluntary provision of written informed consent (including, for the USA, subject authorization under the Health Insurance Portability and Accountability Act (HIPAA)), given before any study-related procedure that is not part of normal medical care and with the understanding that the subject may withdraw consent at any time without prejudice to his or her future medical care.
Key exclusion criteria (24 listed)
- Premature discontinuation of core study 28063.
- Subjects who meet criteria listed below will receive IMP in study 28851:
- All subjects must satisfy the following criteria before Extension Study Day 1 (D1-EXT; defined as the first day of dosing in the extension study) to be eligible for treatment with IMP:
- Willingness and ability to comply with study procedures for the duration of the study.
- To be eligible for treatment with investigational medicinal product (IMP) in study 28851, the subjects must not meet any of the following criteria:
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 |
|---|---|---|
| Atacicept 25 mgSubjects who received atacicept 25 milligram (mg) subcutaneously (SC) as loading dose twice weekly for first 4 weeks, followed by atacicept 25 mg SC for 32 weeks, in 28063 study will continue with atacicept 25 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study. | Drug | Atacicept 25 mg (With Loading) |
| Atacicept 75 mgSubjects who received atacicept 75 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 75 mg SC for 32 weeks, in 28063 study will continued with atacicept 75 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study. | Drug | Atacicept 75 mg (With Loading) |
| Atacicept 150 mgSubjects who received atacicept 150 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 150 mg SC for 32 weeks, in 28063 study will continue with atacicept 150 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study. | Drug | Atacicept 150 mg (With Loading) |
| Atacicept 150 mgSubjects who received placebo SC twice weekly for first 4 weeks, followed by placebo SC for 32 weeks, in 28063 study will continue with atacicept 150 mg (without loading dose) SC once weekly up to 5 years or up to early termination of treatment or early termination of the study. | Drug | Atacicept 150 mg (Without Loading) |
Primary outcome
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity
Time frame: From the first dose of study drug administration up to Week 24
TEAEs were defined as AEs with a start date after or on the date of the first DB treatment injection in ATAMS Extension and that occurred anytime after treatment discontinuation, or up to the day before first Rebif® rescue medication injection in ATAMS Extension. A serious TEAE was an AE that resulted in any of the following: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAE severity was graded as per Qualitative Toxicity Scale. Local injection site reactions (injection site: pain, redness, itching and swelling) throughout ATAMS Extension, starting after the first trial medication administration. If the subject experienced 1 or more of the above injection site symptoms, these were reported with the AE verbatim term "injection site reaction". For all randomized subjects, there was an option of rescue treatment with Rebif® for 1 year beginning with the first injection of Rebif®).
Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Time frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36
Blood pressure (systolic and diastolic) was measured after at least 3 minutes resting, with the subject in the seated position.
Change From Baseline in Vital Signs: Pulse Rate
Time frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36
Change From Baseline in Vital Signs: Temperature
Time frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36
Change From Baseline in Electrocardiogram (ECGs)
Time frame: Baseline, Week 12 and 36
Number of Subjects With Worsened Post Baseline Shift in Immunoglobulin A (IgA), IgG and IgM Levels
Time frame: Baseline up to Week 36
Number of subjects with shifts from normal Grade (Grade 0) at Baseline to worse value at post-baseline (Grade 1 to Grade 4) according to the following criteria: IgA Grade 0: greater than or equal to (>=) lower limit normal (LLN) 0.7 gram per liter (g/L); Grade 1: less than (<) LLN - 0.5 g/L, Grade 2: <0.5g/L -0.3 g/L, Grade 3: <0.3 g/L -0.1 g/L, Grade 4: < 0.1 g/L; IgG Grade 0: >= LLN (7 g/L), Grade 1: < LLN - 5 g/L, Grade 2: <5g/L -4 g/L, Grade 3: <4 g/L -3 g/L and Grade 4: < 3 g/L; IgM Grade 0: >= LLN (0.4 g/L), Grade 1: < LLN - 0.3 g/L, Grade 2: <0.3 g/L -0.2 g/L, Grade 3: <0.2 g/L -0.1 g/L, and Grade 4: < 0.1 g/L are presented in this outcome measure.
Number of Subjects With Positive Neutralizing Antibody (NAb)
Time frame: Baseline, Week 12 and 36
8 secondary outcomes
Number of Subjects With Clinical Attacks/Relapses
Time frame: Baseline up to Week 24
Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Week 12
Time frame: Baseline, Week 12
Change in Multiple Sclerosis Functional Composite (MSFC) Score at Week 12
Time frame: Week 12
Magnetic Resonance Imaging (MRI) Parameters: Number of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject
Time frame: Baseline, Week 12 and 24
Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions (New or Enlarging T2 Lesions) Per Subject
Time frame: Baseline, Week 12 and Week 24
Concentrations of Free and Total Atacicept
Time frame: Baseline and Week 12
Free B-Lymphocyte Stimulator (BLyS) and Free A Proliferation-Inducing Ligand (APRIL) Serum Concentrations.
Time frame: Baseline, Week 12 and 36
Pharmacogenetics/Pharmacogenomics Analysis
Time frame: Day 1 and Week 36
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24613349Kappos L, Hartung HP, Freedman MS, Boyko A, Radu EW, Mikol DD, Lamarine M, Hyvert Y, Freudensprung U, Plitz T, van Beek J; ATAMS Study Group. Atacicept in multiple sclerosis (ATAMS): a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Neurol. 2014 Apr;13(4):353-63. doi: 10.1016/S1474-4422(14)70028-6. Epub 2014 Mar 6.
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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.
Daniel Mikol, MD, PhD study director
EMD Serono
47 sites in 17 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Atacicept 25 mg, Atacicept 75 mg and Atacicept 150 mg in people with Relapsing Multiple Sclerosis, run by EMD Serono at 47 sites in 17 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 4 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: stopped early, as of the sponsor's last update on 20 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 47 sites in Russia, United States, Australia, Ukraine, Netherlands and 12 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 May 2016). 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?
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity (time frame: From the first dose of study drug administration up to Week 24). The study lists 7 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 NCT00853762, which also lists 1 linked publication.
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 20 Mar 2017; AzTrials last refreshed its copy on 27 Oct 2026.