A Study to Evaluate the Efficacy and Safety of ABC008 for Inclusion Body Myositis

Study Overview
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Brief Summary
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A Phase II/III Randomized, Double-blind, Placebo-controlled, Multicenter Study to Determine the Efficacy and Safety of ABC008 in the Treatment of Subjects with Inclusion Body Myositis

Detailed Description
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A Phase II/III Randomized, Double-blind, Placebo-controlled, Multicenter Study to Determine the Efficacy and Safety of ABC008 in the Treatment of Subjects with Inclusion Body Myositis Detailed Description: A Phase II/III Randomized, Double-blind, Placebo-controlled, Multicenter Study to Determine the Efficacy and Safety of ABC008 in the Treatment of Subjects with Inclusion Body Myositis Detailed Description: This is a Phase II/III randomized, double-blind, placebo-controlled, parallel multicenter study with 3 parts. The study will include a sentinel cohort (Part A) of 30 subjects who will receive first three doses of the study drug. Safety data from subjects in the sentinel cohorts will be evaluated by a Data and Safety Monitoring Board (DSMB) before further dosing of the sentinel cohort, as well as initiation of enrollment in the double-blind safety and efficacy cohort (Part B). After completion of Part A or Part B, subjects have the option of enrolling in an open-label long-term extension study or progressing to the pharmacodynamics (PD) recovery cohort (Part C), to evaluate the recovery of the depletion of killer cell lectin-like receptor G1 (KLRG1)+ cells after the end of treatment with ABC008. Efficacy, safety, HRQoL, and HRU assessments will be conducted. Blood samples will be obtained to evaluate the serum PK, PD, and immunogenicity of ABC008 throughout the study.

Official Title
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A Phase II/III Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of ABC008 in the Treatment of Subjects With Inclusion Body Myositis

Conditions
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Inclusion Body Myositis

Intervention / Treatment
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* Drug: ABC008


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult males and females age >40 years at the time of the first dose of study medication; Weight >40 and <150 kg; Diagnosis of either clinico-pathologically defined IBM, clinically defined IBM, or probable IBM according to the European Neuromuscular Centre (ENMC) IBM 2011 research diagnostic criteria (Rose et al., 2013). Documented histopathology results must be available prior to Baseline (Day 1) to confirm eligibility; Able to arise from a chair (with armrests), with use of their arms but without support from another person or device (e.g., cane, walking stick), at Screening and Baseline (Day 1); Able to walk 3 meters, turn around, walk back to the chair, and sit down, with or without assistive device. Once arisen from the chair, subject may use any walking device but cannot be supported by another person, furniture, or a wall; Exclusion Criteria: Any other form of myositis or myopathy other than IBM, e.g., metabolic or drug-induced myopathy, drug-induced myositis, anti-synthetase syndrome, polymyositis or dermatomyositis, cancer-associated myositis (myositis diagnosed within 3 years, either before or after), myositis in overlap with another autoimmune disease (e.g., systemic lupus, systemic sclerosis, rheumatoid arthritis), or muscular dystrophy; Any condition, e.g., severe degenerative arthritis with limited range of motion, which precludes the ability to quantitate muscle strength or perform functional assessments (e.g., mTUG), in the Investigator's opinion;. Presence of another autoimmune or autoinflammatory disease other than indication under study, e.g., rheumatoid arthritis, psoriatic arthritis, axial spondyloarthropathy, inflammatory bowel disease, systemic lupus erythematosus. Subjects with Sjogren's syndrome, T-cell large granular lymphocyte leukemia (T-LGLL), or well-controlled thyroid disease are permitted;

Ages Eligible for Study
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Minimum Age: 40 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 |
| --- | --- |
| Active Comparator: 0.5 mg/kg ABC008<br>Part A - ABC008 N=12 Part B - ABC008 N= 67 | Drug: ABC008<br>* Given by subcutaneous injection<br>|
| Active Comparator: 2.0 mg/kg ABC008<br>Part A - ABC008 N=12 Part B - ABC008 N= 67 | Drug: ABC008<br>* Given by subcutaneous injection<br>|
| Placebo Comparator: Placebo<br>Part A - Placebo N= 6 Part B - Placebo N= 67 | Drug: ABC008<br>* Given by subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A - To determine the safety and tolerability of recurrent dosing of ABC008 in subjects with IBM at 2 SC dose levels. | Safety as assessed by the incidence, type and severity of Treatment Emergent Adverse Events (TEAEs) | From Baseline (week 0) through week 20. | 
| Part B - To determine the efficacy of ABC008 in IBM at two SC dose levels as measured by IBM Functional Rating Scale (IBMFRS) at Week (W)76 | Mean change in IBM Functional Rating Scale (IBMFRS) | From Baseline (week 0) through study completion, an average of 76 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A - Treatment Emergent Serious Adverse Events (TEASAEs) | Incidence, type and severity of TEASAEs. | From Baseline (Day 1) through study completion, an average of 80 weeks. | 
| Part A - Treatment Emergent Adverse Events (TEAEs) onset within 24 hours of Study Medication Administration. | Incidence, type, and severity of TEAEs with onset within 24 hours from the start of any of study medication administration | From Baseline (Day 1) through study completion, an average of 80 weeks. | 
| Part A - Treatment Emergent Adverse Events leading to study medication or study discontinuation. | Incidence of TEAEs leading to study medication or study discontinuation | From Baseline (Day 1) through study completion, an average of 80 weeks. | 
| Part A - Clinically significant changes in standard laboratory parameters, vital signs, and ECGs | Incidence of clinically significant changes in standard laboratory parameters, vital signs, and ECGs | From Baseline (Day 1) through study completion, an average of 80 weeks. | 
| Part A - Adverse Events of Special Interest (AESI) | Incidence of AESIs. | From Baseline (Day 1) through study completion, an average of 80 weeks. | 
| Part B - Manual Muscle Test 12 (MMT 12) | Mean change in MMT 12 | From Baseline (Day 1) through study completion, an average of 76 weeks. | 
| Part B - Hand Grip Dynamometry | Mean change in hand grip strength by dynamometry. | From Baseline (Day 1) through study completion, an average of 76 weeks. | 
| Part B - Quadriceps Dynamometry | Mean change in quadriceps strength by dynamometry. | From Baseline (Day 1) through study completion, an average of 76 weeks. | 
| Part B - Modified Timed Up and Go (mTUG) | Mean change in mTUG. | From Baseline (Day 1) through study completion, an average of 76 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Muscular Diseases, Inflammatory Myopathy, Myositis, Neuromuscular Diseases, Nervous System Disease