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

Regeneron Pharmaceuticals

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Conditions

Sporadic Inclusion Body Myositis

Interventions

Eligibility

Sex: ALLMin age: 45 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Percent change in total lean mass as measured by dual-energy X-ray absorptiometry (DXA)

Time frame: Up to Week 20

Secondary Outcomes

Change in the Inclusion Body Myositis-Functional Rating Scale (IBM-FRS)

Time frame: Up to Week 26

Change in the Sporadic inclusion body myositis (sIBM) Physical Functioning Assessment (sIFA)

Time frame: Up to Week 26

Incidence and severity of treatment-emergent adverse events (TEAEs)

Time frame: Up to Week 30

Percent change in total and regional body composition (including lean mass and fat mass) as measured by DXA

Time frame: Up to Week 30

Absolute change in total and regional body composition (including lean mass and fat mass) as measured by DXA

Time frame: Up to Week 30

Change in the 1-repetition maximum (1-RM) chest press strength

Time frame: Up to Week 26

Change in hand-grip strength as measured by dynamometry

Time frame: Up to Week 26

Change in distance walked in the 6-minute walk test (6MWT)

Time frame: Up to Week 26

Change in time to complete the 10-meter walk test (10MWT)

Time frame: Up to Week 26

Change in instrumented stair climb power

Time frame: Up to Week 26

Change in instrumented, sensor-based sit-to-stand test time

Time frame: Up to Week 26

Change in fear of falling as measured via the Falls Efficacy Scale-International (FES-I)

Time frame: Up to Week 30

Change in Patient Global Impression of Severity assessments (PGIS/PGIC)

Time frame: Up to Week 30

Change in Patient Global Impression of Change Items assessments (PGIS/PGIC)

Time frame: Up to Week 30

Change in Clinician Global Impression of Severity assessments (CGIS/CGIC)

Time frame: Up to Week 30

Change in Clinician Global Impression of Change Items assessments (CGIS/CGIC)

Time frame: 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

Time frame: Up to Week 30

Change in Thigh muscle volume as measured by MRI (sub-study)

Time frame: Up to Week 30

Frequency of falls and near-falls as measured by the Hopkins Falls Grading Scale

Time frame: Up to Week 30

Pharmacokinetics (PK) profile of REGN2477

Assessed via serum concentration of REGN2477 over time

Time frame: Up to Week 30

Pharmacokinetics (PK) profile of REGN1033

Assessed via serum concentration of REGN1033 over time

Time frame: Up to Week 30

Immunogenicity of REGN2477+REGN1033

As determined by the presence or absence of anti-drug antibodies (ADA)

Time frame: Up to Week 30