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

Phase 2
Withdrawn
Conditions
Sporadic Inclusion Body Myositis
Interventions
Drug: REGN2477+REGN1033
Drug: Matching placebo
Registration Number
NCT03710941
Lead Sponsor
Regeneron Pharmaceuticals
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
REGN2477+REGN1033REGN2477+REGN1033Single, sequential, repeat-dose IV or matching placebo
PlaceboMatching placeboSingle, sequential, repeat-dose IV
Primary Outcome Measures
NameTimeMethod
Percent change in total lean mass as measured by dual-energy X-ray absorptiometry (DXA)Up to Week 20
Secondary Outcome Measures
NameTimeMethod
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
Percent change in total and regional body composition (including lean mass and fat mass) as measured by DXAUp to Week 30
Absolute change in total and regional body composition (including lean mass and fat mass) as measured by DXAUp to Week 30
Change in the 1-repetition maximum (1-RM) chest press strengthUp to Week 26
Change in hand-grip strength as measured by dynamometryUp 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
Incidence and severity of treatment-emergent adverse events (TEAEs)Up to Week 30
Change in instrumented stair climb powerUp to Week 26
Change in instrumented, sensor-based sit-to-stand test timeUp 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-36Up 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 ScaleUp to Week 30
Pharmacokinetics (PK) profile of REGN2477Up to Week 30

Assessed via serum concentration of REGN2477 over time

Pharmacokinetics (PK) profile of REGN1033Up to Week 30

Assessed via serum concentration of REGN1033 over time

Immunogenicity of REGN2477+REGN1033Up to Week 30

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

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