Safety and Efficacy of REGN2477+REGN1033 in Patients With Sporadic Inclusion Body Myositis

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the efficacy of REGN2477+REGN1033 in combination on total lean mass, as measured by Dual-energy X-ray absorptiometry (DXA) in patients with sporadic inclusion body myositis (sIBM). The secondary objectives of the study are: To evaluate the efficacy of REGN2477+REGN1033 on the IBM-Functional Rating Scale (IBM-FRS) To evaluate the efficacy of REGN2477+REGN1033 on the sIBM Physical Functioning Assessment (sIFA) To evaluate the safety and tolerability of REGN2477+REGN1033 To evaluate the effects of REGN2477+REGN1033 on body composition by DXA, including appendicular lean mass and total fat mass To evaluate the efficacy of REGN2477+REGN1033 on measures of muscle performance and physical function To evaluate the efficacy of REGN2477+REGN1033 on patient reported outcome measures including the fear of falling, falls and near falls, and health-related quality of life To evaluate the pharmacokinetic(s) (PK) profile of REGN2477+REGN1033, including functional REGN2477 and functional REGN1033 concentrations in serum over time To evaluate the immunogenicity of REGN2477+REGN1033

Official Title
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A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Intravenously Administered REGN2477+REGN1033 in Patients With Sporadic Inclusion Body Myositis

Conditions
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Sporadic Inclusion Body Myositis

Intervention / Treatment
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* Drug: REGN2477+REGN1033
* Drug: Matching placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Men and postmenopausal* women Diagnosed with sIBM based on the European Neuromuscular Centre (ENMC) IBM Research Diagnostic Criteria Ability to walk ≥150 meters, with or without a walking aid such as cane or walker, in 6 minutes. Ability to climb 4 steps of stairs unassisted (may use handrails) Willing and able to comply with clinic visits and study-related procedures Key Exclusion Criteria: Other neurological conditions (eg, hemiplegia post stroke, Parkinson's) or musculo-skeletal conditions (eg, severe osteoarthritis) causing mobility impairment Mini-Mental State Examination (MMSE) score <24 Ongoing, chronic, high-dose (>20 mg prednisone equivalent per day), systemic corticosteroid therapy within 6 weeks prior to screening. Any condition that precludes adequate intake of energy and protein; malnutrition; presence of an eating disorder. Unintentional weight loss of ≥10% in the past 6 months (patient-reported) Hospitalization for heart failure in last year or New York Heart Association Class 4 History of hypertrophic cardiomyopathy Any drugs known to influence muscle mass and performance such as anabolic steroids or growth hormone within 6 weeks prior to screening Unable to fit on the site's DXA scanner table, within borders for scanning of total lean mass Note: Other protocol Inclusion/Exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: REGN2477+REGN1033<br>Single, sequential, repeat-dose IV or matching placebo | Drug: REGN2477+REGN1033<br>* Single, sequential, repeat-dose Intravenous (IV) or matching placebo<br>|
| Experimental: Placebo<br>Single, sequential, repeat-dose IV | Drug: Matching placebo<br>* Single, sequential, repeat-dose Intravenous (IV)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in total lean mass as measured by dual-energy X-ray absorptiometry (DXA) |  | Up to Week 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Inclusion Body Myositis-Functional Rating Scale (IBM-FRS) |  | Up to Week 26 | 
| Change in the Sporadic inclusion body myositis (sIBM) Physical Functioning Assessment (sIFA) |  | Up to Week 26 | 
| Incidence and severity of treatment-emergent adverse events (TEAEs) |  | Up to Week 30 | 
| Percent change in total and regional body composition (including lean mass and fat mass) as measured by DXA |  | Up to Week 30 | 
| Absolute change in total and regional body composition (including lean mass and fat mass) as measured by DXA |  | Up to Week 30 | 
| Change in the 1-repetition maximum (1-RM) chest press strength |  | Up to Week 26 | 
| Change in hand-grip strength as measured by dynamometry |  | Up to Week 26 | 
| Change in distance walked in the 6-minute walk test (6MWT) |  | Up to Week 26 | 
| Change in time to complete the 10-meter walk test (10MWT) |  | Up to Week 26 | 
| Change in instrumented stair climb power |  | Up to Week 26 | 
| Change in instrumented, sensor-based sit-to-stand test time |  | Up to Week 26 | 
| Change in fear of falling as measured via the Falls Efficacy Scale-International (FES-I) |  | Up to Week 30 | 
| Change in Patient Global Impression of Severity assessments (PGIS/PGIC) |  | Up to Week 30 | 
| Change in Patient Global Impression of Change Items assessments (PGIS/PGIC) |  | Up to Week 30 | 
| Change in Clinician Global Impression of Severity assessments (CGIS/CGIC) |  | Up to Week 30 | 
| Change in Clinician Global Impression of Change Items assessments (CGIS/CGIC) |  | Up to Week 30 | 
| Change in 36-item Short Form Health Survey (SF-36), including the Physical Function Items (PF-10) and the Vitality Scale of the SF-36 |  | Up to Week 30 | 
| Change in Thigh muscle volume as measured by MRI (sub-study) |  | Up to Week 30 | 
| Frequency of falls and near-falls as measured by the Hopkins Falls Grading Scale |  | Up to Week 30 | 
| Pharmacokinetics (PK) profile of REGN2477 | Assessed via serum concentration of REGN2477 over time | Up to Week 30 | 
| Pharmacokinetics (PK) profile of REGN1033 | Assessed via serum concentration of REGN1033 over time | Up to Week 30 | 
| Immunogenicity of REGN2477+REGN1033 | As determined by the presence or absence of anti-drug antibodies (ADA) | Up to Week 30 |