Efficacy, Safety, and Tolerability of Plovamer Acetate (Pathway 1)

Study Overview
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Brief Summary
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This is a Phase 2, randomized, rater-blinded, 5-arm, parallel-group trial that will test 4 doses of plovamer acetate against the active comparator Copaxone in subjects with Relapsing Remitting Multiple Sclerosis (RRMS). The trial will be conducted on an outpatient basis for minimum treatment duration of 40 weeks.

Official Title
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A Phase II, Randomized, Multi-center, Parallel-group, Rater-blinded Study to Evaluate the Efficacy, Safety and Tolerability of 0.5 mg, 3 mg, 10 mg and 20 mg Plovamer Acetate Doses Compared to Copaxone in Patients With Relapsing Remitting Multiple Sclerosis

Conditions
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Relapsing Remitting Multiple Sclerosis

Intervention / Treatment
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* Drug: Plovamer acetate 0.5 milligram (mg)
* Drug: Copaxone 20 mg
* Drug: Plovamer acetate 3 mg
* Drug: Plovamer acetate 10 mg
* Drug: Plovamer acetate 20 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, between the ages of 18 and 60 years Subject is able to learn and self-administer subcutaneous injections (a care-giver may be trained to inject the subject) Subjects must have a current diagnosis of Relapsing Remitting Multiple Sclerosis (RRMS) (according to the 2010 McDonald MS diagnostic criteria) Other protocol defined inclusion criteria could apply Exclusion Criteria: Any multiple sclerosis categorized as primary progressive, secondary progressive or progressive relapsing Allergy to mannitol, plovamer acetate, Copaxone (glatiramer acetate), Gd contrast for MRI Any requirement for continuous systemic glucocorticoid administration during the trial period. (Note: Treatment with interferons such as Avonex®, Rebif®, or Betaseron® will be allowed until the baseline visit, as no wash-out period is needed) Contraindication to Copaxone use Other protocol defined exclusion criteria could apply

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Plovamer acetate 0.5 milligram (mg)<br>Plovamer acetate was administered at a dose of 0.5 mg as weekly subcutaneous injection for 40 weeks up to a maximum of 14 months. | Drug: Plovamer acetate 0.5 milligram (mg)<br>* Plovamer acetate was administered at a dose of 0.5 mg as weekly subcutaneous injection for 40 weeks up to a maximum of 14 months.<br>|
| Experimental: Plovamer acetate 3 mg<br>Plovamer acetate was administered at a dose of 3 mg as weekly subcutaneous injection for 40 weeks up to a maximum of 14 months. | Drug: Plovamer acetate 3 mg<br>* Plovamer acetate was administered at a dose of 10 mg as weekly subcutaneous injection for 40 weeks up to a maximum of 14 months.<br>|
| Experimental: Plovamer acetate 10 mg<br>Plovamer acetate was administered at a dose of 10 mg as weekly subcutaneous injection for 40 weeks up to a maximum of 14 months. | Drug: Plovamer acetate 10 mg<br>* Plovamer acetate was administered as two subcutaneous injection of 10 mg weekly for 40 weeks up to a maximum of 14 months.<br>|
| Experimental: Plovamer acetate 20 mg<br>Plovamer acetate was administered as two subcutaneous injection of 10 mg weekly for 40 weeks up to a maximum of 14 months. | Drug: Plovamer acetate 20 mg<br>* Copaxone was administered at a dose of 20 mg as subcutaneous injection once daily for 40 weeks up to a maximum of 14 months.<br>|
| Active Comparator: Copaxone 20 mg<br>Copaxone was administered at a dose of 20 mg as subcutaneous injection once daily for 40 weeks up to a maximum of 14 months. | Drug: Copaxone 20 mg<br>* Plovamer acetate was administered at a dose of 3 mg as weekly subcutaneous injection for 40 weeks up to a maximum of 14 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Number of Time Constant 1 (T1) Gadolinium (Gd)-Enhancing Lesions Per Subject and Scan | Time Constant 1 (T1) Gadolinium (Gd)-Enhancing Lesions per Subject and Scan was calculated using 5 serial magnetic resonance imaging (MRI) scans. | Baseline , Week 12, 24, 28, 32, 36, 40 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Annualized Relapse Rate (ARR) | Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. These new or worsening symptoms should be noted by the patient and must be accompanied by at least one of the following: An increase of greater than or equal to (>=) 1 grade in >=2 functional scales of the Expanded Disability Status Scale (EDSS) or an increase of >=2 grades in 1 functional scale of the EDSS or an increase of >= 0.5 or an increase of >=1.0 in EDSS if the previous EDSS was 0. Annualized Relapse Rate was calculated as = 365.25 x (Number of relapses during Treatment Period) per (Number of days on treatment during Treatment Period). | Baseline up to Week 40 | 
| Percentage of Subjects Remaining Relapse-Free | Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. These new or worsening symptoms should be noted by the patient and must be accompanied by at least one of the following: An increase of greater than or equal to (>=) 1 grade in >=2 functional scales of the Expanded Disability Status Scale (EDSS) or an increase of >=2 grades in 1 functional scale of the EDSS or an increase of >= 0.5 or an increase of >=1.0 in EDSS if the previous EDSS was 0. | Baseline up to Week 40 | 
| Mean Number of New T1 Gadolinium (Gd)-Enhancing Lesions Per Subject and Scan | T1 Gd-enhancing lesions per subject and scan was measured using 5 serial MRI scans. | Weeks 12, 24, 28, 32, 36, 40 | 
| Mean Number of New or Enlarging Time Constant 2 (T2) Lesions Per Subject and Scan | New or enlarging Time Constant 2 (T2) lesions per subject and scan was calculated using 5 serial MRI scans. | Weeks 12, 24, 28, 32, 36,40 | 
| Mean Number of New, Unenhancing T1 Lesions (Black Holes) Per Subject and Scan | New, unenhancing T1 lesions (Black Holes) per subject and scan was calculated using 5 Serial MRIs. | Weeks 12, 24, 28, 32, 36, 40 | 
| Mean Change From Baseline in Volume of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject and Scan | Change from baseline in volume of T1 Gd-enhancing lesions per subject was calculated using 5 Serial MRI Scans. | Baseline, Weeks 12, 24, 28, 32, 36, 40 | 
| Mean Change From Baseline in Volume of T2 Gadolinium (Gd)-Enhancing Lesions Per Subject and Scan | Change from baseline per subjects in volume of T2 Gd-enhancing lesions was calculated using 5 series MRI scan. | Baseline, Weeks 12, 24, 28, 32, 36, 40 | 
| Time to First Relapse | Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. These new or worsening symptoms should be noted by the patient and must be accompanied by at least one of the following: An increase of greater than or equal to (>=) 1 grade in >=2 functional scales of the Expanded Disability Status Scale (EDSS) or an increase of >=2 grades in 1 functional scale of the EDSS or an increase of >= 0.5 or an increase of >=1.0 in EDSS if the previous EDSS was 0. | Baseline up to Week 40 | 
| Mean Change From Baseline in Brain Volume Per Subject | Change from baseline in brain volume per subject was calculated using 5 series MRI scan. | Baseline, Weeks 24, 28, 32, 36, 40 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, Relapsing Remitting, Plovamer acetate, Copaxone