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
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
272
Given by subcutaneous injection
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)
Time frame: 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)
Time frame: From Baseline (week 0) through study completion, an average of 76 weeks
Part A - Treatment Emergent Serious Adverse Events (TEASAEs)
Incidence, type and severity of TEASAEs.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: From Baseline (Day 1) through study completion, an average of 80 weeks.
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Part A - Adverse Events of Special Interest (AESI)
Incidence of AESIs.
Time frame: 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
Time frame: 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.
Time frame: From Baseline (Day 1) through study completion, an average of 76 weeks.
Part B - Quadriceps Dynamometry
Mean change in quadriceps strength by dynamometry.
Time frame: From Baseline (Day 1) through study completion, an average of 76 weeks.
Part B - Modified Timed Up and Go (mTUG)
Mean change in mTUG.
Time frame: From Baseline (Day 1) through study completion, an average of 76 weeks.