An Intravenous Infusion Study of rHIgM22 in Patients With Multiple Sclerosis Immediately Following a Relapse

Study Overview
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Brief Summary
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This is a Phase 1, multi-center, double-blind, randomized, placebo-controlled, dose-escalation study in subjects with relapsing Multiple Sclerosis (MS). The primary outcome will be the safety and tolerability of a single dose of rHIgM22 in relapsing MS subjects.

Official Title
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A Double-Blind, Placebo-Controlled, Single Ascending Dose Intravenous Infusion Study of rHIgM22 in Patients With Multiple Sclerosis Immediately Following a Relapse

Conditions
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Multiple Sclerosis, Acute Relapsing

Intervention / Treatment
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* Drug: rHIgM22
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females (18-70 years of age; < 104 kg) Capable of giving informed consent Meet diagnostic criteria for MS, as defined by revised (2010) McDonald criteria Present with a clinical acute relapse defined as a new or worsening neurological symptoms attributable to MS preceded by a stable or improving neurological state of at least 30 days, not associated with fever or infection, lasting at least 24 hours and accompanied by an objective physical (neurological) exam finding as confirmed by the Investigator Has at least one new, identifiable, measurable and active lesion on MRI (Gd+) meeting the criteria of the imaging charter. Exclusion Criteria: Certain specified co-morbidities (including pregnancy) Taking certain proscribed medications A medical regimen that has changed in the month prior to screening Inability to undergo requisite MRI evaluations Drug or alcohol abuse Any other reason for which, in the opinion of the Investigator, the subject should not participate in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rHIgM22<br>Patients will be enrolled sequentially in 2 separate cohorts, representing escalating dose levels. Each dose cohort will comprise 15 subjects, randomly assigned to receive either rHIgM22 (n=10) or placebo (n=5). | Drug: rHIgM22<br>* Administered via IV infusion<br>* Other names: M22;|
| Placebo Comparator: Placebo<br>Patients will be enrolled sequentially in 2 separate cohorts, representing escalating dose levels. Each dose cohort will comprise 15 subjects, randomly assigned to receive either rHIgM22 (n=10) or placebo (n=5). | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of single ascending doses of rHIgM22 in patients with MS immediately following a relapse as measured by the number of patients with Adverse Events (AEs) | Assessed by review of the AEs, including Serious Adverse Events (SAEs), clinical symptoms and signs, clinical laboratory tests and Electrocardiogram (ECGs). | Up to 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum measured plasma concentration (Cmax) of single ascending doses of rHIgM22 |  | Pre-dose (day 1), specified time points up to 48 hours post treatment | 
| Time to maximum plasma concentration (Tmax) of single ascending doses of rHIgM22 |  | Pre-dose (day 1), specified time points up to 48 hours post treatment | 
| Half-life (T1/2) of single ascending doses of rHIgM22 |  | Pre-dose (day 1), specified time points up to 48 hours post treatment | 
| Area under the concentration curve from time 0 to the concentration at last time point (AUC0-last) of single ascending doses of rHIgM22 |  | Pre-dose (day 1), specified time points up to 48 hours post treatment | 
| Immunogenicity profile of single ascending doses of rHIgM22 | Blood samples will be collected from subjects post treatment for assessment to detect the presence of anti-drug antibodies and neutralizing antibodies. | Specified time points up to 180 days post treatment | 
| The Expanded Disability Status Scale (EDSS) |  | Screening, specified time points up to 180 days post treatment |