A Multiple Dose Study of ABT-555 in Subjects With Relapsing Forms of Multiple Sclerosis

Study Overview
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Brief Summary
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This study seeks to evaluate the safety, tolerability, pharmacokinetics (PK) and immunogenicity of ABT-555 in participants with relapsing forms of multiple sclerosis (RFMS).

Official Title
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An Escalating Multiple Dose Study of ABT-555 in Subjects With Relapsing Forms of Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: ABT-555
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Currently receiving one of the following MS medications for at least 3 months: beta-interferon (any formulation including the pegylated form), glatiramer acetate (Copaxone®, others), teriflunomide (Aubagio®), fingolimod (Gilenya®), or dimethyl fumarate (Tecfidera®); OR Has not been treated with an MS immunotherapy for the past 6 months (12 months if they previously received cyclophosphamide or alemtuzumab); OR Treatment naïve with established MS diagnosis per criteria by a neurologist. Diagnosis of relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) according to revised McDonald criteria Baseline Expanded Disability Status Scale (EDSS) between 0 and 6.0, inclusive. Brain MRI scan at Screening that did not show evidence of overt vascular lesions, masses, mass effect or other abnormalities other than those compatible with MS, which would preclude the participant from undergoing a lumbar puncture/spinal tap for CSF collection Exclusion Criteria: Diagnosis of primary progressive MS. Anticipated maintenance immunomodulator change, either agent or dose An MS relapse that occurred within the 30 days prior to randomization AND/OR the participant has not stabilized from a previous relapse prior to randomization Participants for whom MRI is contraindicated Participants who have claustrophobia that cannot be medically managed or are unable to lie still for 1 hour or more for the imaging procedures Findings on brain MRI scan indicating any clinically significant brain abnormality other than MS Contraindication for lumbar puncture

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 2<br>Participants will receive multiple doses of ABT-555 or placebo | Drug: ABT-555<br>* Intravenous Infusion<br>* Other names: Elezanumab;Other: Placebo<br>* Intravenous Infusion<br>|
| Experimental: Group 3<br>Participants will receive multiple doses of ABT-555 or placebo | Drug: ABT-555<br>* Intravenous Infusion<br>* Other names: Elezanumab;Other: Placebo<br>* Intravenous Infusion<br>|
| Experimental: Group 1<br>Participants will receive multiple doses of ABT-555 or placebo | Drug: ABT-555<br>* Intravenous Infusion<br>* Other names: Elezanumab;Other: Placebo<br>* Intravenous Infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and percentage of participants reporting adverse events |  | Throughout study from Day 1 to Day 176 | 
| Concentration of anti-drug antibody (ADA) titers of ABT-555 |  | Day 1 to Day 176 | 
| Time to Maximum observed plasma concentration (Tmax) of ABT-555 |  | Day 1 to Day 176 | 
| Maximum observed plasma concentration (Cmax) of ABT-555 |  | Day 1 to Day 176 | 
| Area under the concentration curve (AUC) of ABT-555 |  | Day 1 to Day 176 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants who experience relapse and disability progression |  | Throughout the study to Day 176 | 
| Lesion volume of new, newly enlarging T2 hyperintense lesions |  | Throughout study from Day 0 to Day 113 | 
| Number of new, newly-enlarging T2 hyperintense lesions |  | Throughout study from Day 0 to Day 113 | 
| Total number of new Gadolinium-enhancing T1 lesions |  | Throughout study from Day 0 to Day 113 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsing-remitting, Secondary progressive, Relapsing forms