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

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

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

Conditions
-----------------
Multiple Sclerosis (MS)

Intervention / Treatment
-----------------
* Drug: elezanumab
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant has diagnosis of relapsing remitting multiple sclerosis (RRMS) or secondary-progressive multiple sclerosis (SPMS) with relapses within the past 24 months. Participant has cranial magnetic resonance imaging (MRI) demonstrating lesion(s) consistent with multiple sclerosis (MS). Participant has evidence of physical disability according to Expanded Disability Status Scale (EDSS) or Timed 25-Foot Walk (T25FW) or 9-Hole Peg Test. Exclusion Criteria: - Participants must not have experienced or be recovering from a clinical MS relapse within 6 months of Screening.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 double-blind placebo by intravenous infusion. | Drug: placebo<br>* solution for infusion<br>|
| Experimental: Elezanumab Dose 1<br>Participants randomized to receive double-blind elezanumab Dose 1 by intravenous infusion. | Drug: elezanumab<br>* solution for infusion<br>* Other names: ABT-555;|
| Experimental: Elezanumab Dose 2<br>Participants randomized to receive double-blind elezanumab Dose 2 by intravenous infusion. | Drug: elezanumab<br>* solution for infusion<br>* Other names: ABT-555;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Overall Response Score (ORS) at Week 52 | 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 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). 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 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
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Relapsing multiple sclerosis, Multiple sclerosis, Elezanumab, ABT-555