Clinical trial NCT03710941: Safety and Efficacy of REGN2477+REGN1033 in Patients With Sporadic Inclusion Body Myositis
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Sporadic Inclusion Body Myositis
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-10-18
Enrollment: 0
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Percent change in total lean mass as measured by dual-energy X-ray absorptiometry (DXA)
timeFrame: Up to Week 20
Secondary outcomes:
measure: Change in the Inclusion Body Myositis-Functional Rating Scale (IBM-FRS)
timeFrame: Up to Week 26
measure: Change in the Sporadic inclusion body myositis (sIBM) Physical Functioning Assessment (sIFA)
timeFrame: Up to Week 26
measure: Incidence and severity of treatment-emergent adverse events (TEAEs)
timeFrame: Up to Week 30
measure: Percent change in total and regional body composition (including lean mass and fat mass) as measured by DXA
timeFrame: Up to Week 30
measure: Absolute change in total and regional body composition (including lean mass and fat mass) as measured by DXA
timeFrame: Up to Week 30
measure: Change in the 1-repetition maximum (1-RM) chest press strength
timeFrame: Up to Week 26
measure: Change in hand-grip strength as measured by dynamometry
timeFrame: Up to Week 26
measure: Change in distance walked in the 6-minute walk test (6MWT)
timeFrame: Up to Week 26
measure: Change in time to complete the 10-meter walk test (10MWT)
timeFrame: Up to Week 26
measure: Change in instrumented stair climb power
timeFrame: Up to Week 26
measure: Change in instrumented, sensor-based sit-to-stand test time
timeFrame: Up to Week 26
measure: Change in fear of falling as measured via the Falls Efficacy Scale-International (FES-I)
timeFrame: Up to Week 30
measure: Change in Patient Global Impression of Severity assessments (PGIS/PGIC)
timeFrame: Up to Week 30
measure: Change in Patient Global Impression of Change Items assessments (PGIS/PGIC)
timeFrame: Up to Week 30
measure: Change in Clinician Global Impression of Severity assessments (CGIS/CGIC)
timeFrame: Up to Week 30
measure: Change in Clinician Global Impression of Change Items assessments (CGIS/CGIC)
timeFrame: Up to Week 30
measure: 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
timeFrame: Up to Week 30
measure: Change in Thigh muscle volume as measured by MRI (sub-study)
timeFrame: Up to Week 30
measure: Frequency of falls and near-falls as measured by the Hopkins Falls Grading Scale
timeFrame: Up to Week 30
measure: Pharmacokinetics (PK) profile of REGN2477
timeFrame: Up to Week 30
measure: Pharmacokinetics (PK) profile of REGN1033
timeFrame: Up to Week 30
measure: Immunogenicity of REGN2477+REGN1033
timeFrame: Up to Week 30
Other outcomes:
Locations:
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: