A Study to Assess the Safety and Efficacy of Elezanumab When Added to Standard of Care in Progressive Forms of Multiple Sclerosis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of elezanumab in participants with progressive Multiple Sclerosis (PMS).

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study to Assess the Safety and Efficacy of Elezanumab When Added to Standard of Care in Progressive Forms of Multiple Sclerosis

Conditions
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Multiple Sclerosis (MS)

Intervention / Treatment
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* Drug: elezanumab
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of primary-progressive multiple sclerosis (PPMS) or non-relapsing secondary-progressive multiple sclerosis (SPMS) and no relapses for at least 24 months. Evidence of physical disability according to Expanded Disability Status Scale (EDSS) or Timed 25-Foot Walk (T25FW) or 9-Hole Peg Test. Exclusion Criteria: Treatment with any of the following within the 6 months prior to Screening: natalizumab; cyclosporine; azathioprine; methotrexate; mycophenolate mofetil; intravenous immunoglobulin (IVIg); any interferon product; and intravenous (IV), oral, or intrathecal corticosteroids for the purposes of disease modification. Treatment with the following within 1 year prior to Screening: cyclophosphamide or alemtuzumab.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants randomized to receive placebo by intravenous infusion. | Drug: placebo<br>* solution for infusion<br>|
| Experimental: Elezanumab 400mg Dose<br>Participants randomized to receive 400mg of elezanumab by intravenous infusion. | Drug: elezanumab<br>* solution for infusion<br>* Other names: ABT-555;|
| Experimental: Elezanumab 1800 mg Dose<br>Participants randomized to receive 1800mg of elezanumab by intravenous infusion. | Drug: elezanumab<br>* solution for infusion<br>* Other names: ABT-555;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Overall Response Score (ORS) | The ORS is a composite score derived from 4 components: Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test in the dominant hand (9HPT-D), and 9HPT in the non-dominant hand (9HPT-ND). Clinically significant worsening = -1, no change = 0, clinically significant improvement = +1. The ORS is the sum of these scores for the EDSS: Timed 25-Foot Walk, 9-Hole Peg Test-dominant, and 9-Hole Peg Test-nondominant and ranges from -4 to + 4. | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disability Improvement Response Rate | Disability improvement response rate is assessed based on the Expanded Disability Status Scale Plus (EDSS+). EDSS+ is comprised of Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW) and 9-Hole Peg Tests (9HPT). | Week 52 | 
| Overall Response Score (ORS) | The ORS is a composite score derived from 4 components: Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test in the dominant hand (9HPT-D), and 9HPT in the non-dominant hand (9HPT-ND). | Week 12 | 
| Overall Response Score (ORS) | The ORS is a composite score derived from 4 components: Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test in the dominant hand (9HPT-D), and 9HPT in the non-dominant hand (9HPT-ND). Clinically significant worsening = -1, no change = 0, clinically significant improvement = +1. The ORS is the sum of these scores for the EDSS, Timed 25-Foot Walk, 9-Hole Peg Test-dominant and 9-Hole Peg Test-non-dominant and ranges from -4 to + 4. | Week 24 | 
| Overall Response Score (ORS) | The ORS is a composite score derived from 4 components: Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test in the dominant hand (9HPT-D), and 9HPT in the non-dominant hand (9HPT-ND). Clinically significant worsening = -1, no change = 0, clinically significant improvement = +1. The ORS is the sum of these scores for the EDSS, Timed 25-Foot Walk, 9-Hole Peg Test-dominant and 9-Hole Peg Test-non-dominant and ranges from -4 to + 4. | Week 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Progressive multiple sclerosis, Elezanumab, ABT-555