Clinical Study to Evaluate the Efficacy, Safety, and Tolerability of ACT-128800 in Patients With Relapsing-remitting Multiple Sclerosis

Study Overview
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Brief Summary
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This study will assess the efficacy, safety, and tolerability of ACT-128800 in patients with relapsing-remitting multiple sclerosis.

Official Title
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Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-finding Study to Evaluate the Efficacy, Safety, and Tolerability of Three Doses of ACT-128800, an Oral S1P1 Receptor Agonist, Administered for Twenty-four Weeks in Patients With Relapsing-remitting Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: ACT-128800 Dose 1
* Drug: Placebo
* Drug: ACT-128800 Dose 2
* Drug: ACT-128800 Dose 3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult males and females Diagnosis of RRMS as defined by the revised (2005) McDonald Diagnostic Criteria for Multiple Sclerosis (MS). Signed inform consent prior to initiation of any study-mandated procedure. Exclusion Criteria: A diagnosis of MS categorized as primary progressive or secondary progressive or progressive relapsing. Patients currently treated for an autoimmune disorder other than MS. Contraindications for MRI. Ongoing bacterial, viral, or fungal infection. History or presence of malignancy. Additional inclusion and exclusion criteria apply with respect to medical conditions and concomitant treatments which could affect patients' risk from participating in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: ACT-128800 Dose 1<br>ACT-128800 Dose 1 | Drug: ACT-128800 Dose 1<br>* ACT-128800 (Dose 1) administered orally once daily<br>|
| Experimental: ACT-128800 Dose 2<br>ACT-128800 Dose 2 | Drug: ACT-128800 Dose 2<br>* ACT-128800 (Dose 2) administered orally once daily<br>|
| Experimental: ACT-128800 Dose 3<br>ACT-128800 Dose 3 | Drug: ACT-128800 Dose 3<br>* ACT-128800 (Dose 3) administered orally once daily<br>|
| Placebo Comparator: Placebo<br>Matching placebo | Drug: Placebo<br>* Matching placebo administered orally once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Number of New T1 Gadolinium-Enhancing (Gd+) Lesions on Magnetic Resonance Imaging (MRI) Scan From Week 12 to Week 24 | Cumulative Number of new T1 gadolinium-enhancing (Gd+) lesions per year on magnetic resonance imaging (MRI) scan from Week 12 to Week 24 were reported. Negative binomial (NB) regression analysis on Per protocol analysis set and imputation was applied for the missing data. Here, MS signifies multiple sclerosis. | From Week 12 to 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Confirmed Relapse Rate | Relapse: occurrence of acute episode of one or more new symptoms or worsened symptoms of Multiple Sclerosis (MS), not associated with fever/infection and lasting 24 hours after stable 30 days period. Confirmed relapse: increase from baseline at least 0.5 point Expanded Disability Status Scale (EDSS) score or increase of one point in one, two or three Functional Systems (FS), excluding bowel/bladder and cerebral/mental FS. EDSS and FS scores are based on neurological examination for assessing its impairment in MS. Among eight FS, seven are ordinal clinical rating scales ranging from 0-5 or 6 with higher scale indicating overall functional impairment assessing Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel/Bladder and Cerebral functions. Rating individual FS scores is used to rate EDSS with information concerning gait and use of assistance. EDSS is ordinal clinical scale ranges 0 (normal neurological examination) to 10(death due to MS) | Up to 24 weeks | 
| Number of Participants With First Confirmed Relapse as Assessed by Kaplan-Meier Estimate From Baseline to Week 24 | Relapse: occurrence of acute episode of one or more new symptoms or worsened symptoms of MS, not associated with fever/infection and lasting 24 hours after stable 30 days period. Confirmed relapse: increase from baseline at least 0.5 point Expanded Disability Status Scale (EDSS) score or increase of one point in one, two or three Functional Systems (FS), excluding bowel/bladder and cerebral/mental FS. EDSS and FS scores are based on neurological examination for assessing its impairment in MS. Among eight FS, seven are ordinal clinical rating scales ranging from 0-5 or 6 with higher scale indicating overall functional impairment assessing Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel/Bladder and Cerebral functions. Rating individual FS scores is used to rate EDSS with information concerning gait and use of assistance. EDSS is ordinal clinical scale ranges 0 (normal neurological examination) to 10(death due to MS). Kaplan-Meier estimate used for Outcome Measure analysis. | Baseline to Week 24 |