Clinical trial NCT05721573: A Study to Evaluate the Efficacy and Safety of ABC008 for Inclusion Body Myositis
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Inclusion Body Myositis
Keywords: Muscular Diseases
Inflammatory Myopathy
Myositis
Neuromuscular Diseases
Nervous System Disease
Lead sponsor: Abcuro, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
First posted: 2023-02-10
Enrollment: 231
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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;

Primary outcomes:
measure: Part A - To determine the safety and tolerability of recurrent dosing of ABC008 in subjects with IBM at 2 SC dose levels.
timeFrame: From Baseline (week 0) through week 20.
measure: 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
timeFrame: From Baseline (week 0) through study completion, an average of 76 weeks
Secondary outcomes:
measure: Part A - Treatment Emergent Serious Adverse Events (TEASAEs)
timeFrame: From Baseline (Day 1) through study completion, an average of 80 weeks.
measure: Part A - Treatment Emergent Adverse Events (TEAEs) onset within 24 hours of Study Medication Administration.
timeFrame: From Baseline (Day 1) through study completion, an average of 80 weeks.
measure: Part A - Treatment Emergent Adverse Events leading to study medication or study discontinuation.
timeFrame: From Baseline (Day 1) through study completion, an average of 80 weeks.
measure: Part A - Clinically significant changes in standard laboratory parameters, vital signs, and ECGs
timeFrame: From Baseline (Day 1) through study completion, an average of 80 weeks.
measure: Part A - Adverse Events of Special Interest (AESI)
timeFrame: From Baseline (Day 1) through study completion, an average of 80 weeks.
measure: Part B - Manual Muscle Test 12 (MMT 12)
timeFrame: From Baseline (Day 1) through study completion, an average of 76 weeks.
measure: Part B - Hand Grip Dynamometry
timeFrame: From Baseline (Day 1) through study completion, an average of 76 weeks.
measure: Part B - Quadriceps Dynamometry
timeFrame: From Baseline (Day 1) through study completion, an average of 76 weeks.
measure: Part B - Modified Timed Up and Go (mTUG)
timeFrame: From Baseline (Day 1) through study completion, an average of 76 weeks.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Neuromuscular Research Center
state: Arizona
city: Irvine
country: United States
facility: University of California Irvine Medical Center (UCIMC) - Amyotrophic Lateral Sclerosis (ALS) and Neuromuscular Center
state: California
city: Los Angeles
country: United States
facility: Keck Hosptial of USC
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford Neuroscience Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital Anschutz Outpatient Pavillion
state: Colorado
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Chicago
country: United States
facility: Northwestern Memorial Hospital, Department of Neurology (Clinic)
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Neuromuscular Diagnostic Center - Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Womens Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York City
country: United States
facility: Hospital for Special Surgery
state: New York
city: New York
country: United States
facility: Columbia University Medical Center / The Neurological Institute of New York
state: New York
city: Durham
country: United States
facility: Duke Neurological Disorders Clinic -1L
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forrest School of Medicine
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Hershey
country: United States
facility: Penn State Health Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburg
country: United States
facility: UPMC Arthritis and Autoimmunity Center, Falk Clinic
state: Pennsylvania
city: Austin
country: United States
facility: Austin Neuromuscular Center
state: Texas
city: Dallas
country: United States
facility: Texas Neurology
state: Texas
city: Houston
country: United States
facility: Nerve and Muscle Center of Texas
state: Texas
city: Henrico
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center - Montlake
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Saint Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Nedlands
country: Australia
facility: Perron Institute for Neurological and Translational Science
state: Western Australia
city: Gent
country: Belgium
facility: AZ Sint-Lucas & Volkskliniek
city: Calgary
country: Canada
facility: Heritage Medical Research Clinic - University of Calgary
state: Alberta
city: Montréal
country: Canada
facility: Genge Partners Inc.
state: Quebec
city: Paris
country: France
facility: Hospital Pitie-Salpetriere - AP-HP
city: Berlin
country: Germany
facility: Krankenhaus und Poliklinik Rüdersdorf GmbH
city: Düsseldorf
country: Germany
facility: University Hosptial Duesseldorf
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust, National Hospital for Neurology and Neurosurgery (NHNN)
city: Salford
country: United Kingdom
facility: Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust
Study officials:
References: