A Phase 2 Study of Atacicept in Subjects With Relapsing Multiple Sclerosis (ATAMS)

Study Overview
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Brief Summary
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To evaluate the safety and tolerability of atacicept and to explore if atacicept reduces central nervous system inflammation in subjects with relapsing multiple sclerosis (RMS) as assessed by frequent magnetic resonance imaging (MRI). This study is randomised. Study medication is administered via subcutaneous (under the skin) injections.

Official Title
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A Four-Arm Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Study to Evaluate the Safety, Tolerability and Efficacy as Assessed by Frequent MRI Measures of 3 Doses of Atacicept Monotherapy in Subjects With Relapsing Multiple Sclerosis (RMS) Over a 36 Week Treatment Course

Conditions
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Relapsing Multiple Sclerosis

Intervention / Treatment
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* Drug: Atacicept
* Drug: Atacicept
* Drug: Atacicept
* Drug: Placebo matched to atacicept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Diagnosis of RMS (as per McDonald criteria, 2005) Other protocol-defined inclusion criteria could apply. Exclusion Criteria: Have primary progressive multiple sclerosis (MS) Have secondary progressive MS without superimposed relapses Relevant cardiac, hepatic and renal diseases as specified in the protocol Pretreatment with immunosuppressants and immunomodulating drugs as specified in the protocol Clinical significant abnormalities in blood cell counts and immunoglobulin levels as specified in the protocol Clinical significant acute or chronic infections as specified in the protocol Other protocol-defined exclusion criteria could apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atacicept 25 mg<br> | Drug: Atacicept<br>* Atacicept will be administered subcutaneously at a dose of 25 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 32 weeks.<br>|
| Experimental: Atacicept 75 mg<br> | Drug: Atacicept<br>* Atacicept will be administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 32 weeks.<br>|
| Experimental: Atacicept 150 mg<br> | Drug: Atacicept<br>* Atacicept will be administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo matched to atacicept<br>* Placebo matched to atacicept will be administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Number of Time Constant 1 (T1) Gadolinium (Gd)-Enhancing Lesions Per Participant Per Scan | Analysis of T1 Gd-enhancing lesions was done using magnetic resonance imaging (MRI) scans. Only post-baseline scans were included in the calculation of this endpoint (excluding the Study Day 1 scan which had been conducted before first dosing). | Weeks 12 to 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of New T1 Gd-enhancing Lesions Per Participant | Analysis of new T1 Gd-enhancing lesions was done using MRI scans. | Weeks 12, 24, 36 | 
| Percentage of Participants Free From Relapses | A relapse was defined as the fulfillment of all the following criteria: a) 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; b) absence of fever or known infection (fever with temperature [axillary, orally, or intrauriculary] greater than (>) 37.5 degrees Celsius or 99.5 degrees Fahrenheit); and c) objective neurological impairment, correlating with the participant'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. Percentage of participants free from relapses during 36-week treatment period was reported. | Baseline up to Week 36 | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. Treatment-emergent are events between first dose of study drug up to 12 weeks after the last dose of the study drug that were absent before treatment or that worsened relative to pretreatment state. Number of subjects with TEAEs included subjects with both non serious and serious TEAEs. | From the first dose of study drug administration up to 12 weeks after the last dose of the study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsing Multiple Sclerosis, Atacicept