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

Trial ID: 2022-501925-19-00
Protocol: ABC008-IBM-201
Sponsor: Abcuro Inc.

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Diseases & Conditions

Inclusion body myositis

Objectives

The primary objective of this Phase II/III randomized, double-blind, placebo-controlled, multicenter study is to determine the **efficacy** of ABC008 in the treatment of subjects with **inclusion body myositis** (IBM) at two subcutaneous (SC) dose levels. This will be assessed using the IBM Functional Rating Scale (IBMFRS) at Week 76. The clinical relevance of this objective lies in its potential to provide a new therapeutic option for IBM, a progressive muscle disorder with limited treatment options. Additionally, the study aims to evaluate the safety and tolerability of SC ABC008 in subjects with IBM, which is crucial for understanding the risk-benefit profile of the treatment.

The secondary objectives focus on further evaluating the efficacy of SC ABC008 in subjects with IBM at Week 76 through various measures:

Manual Muscle Testing (MMT) 12
Grip strength by dynamometry
Strength of quadriceps by dynamometry
Modified Timed Up and Go test (mTUG)

These measures provide a comprehensive assessment of muscle function and strength, which are critical parameters in the management of IBM.

Participants

The clinical trial involves a total of **195 participants** diagnosed with **inclusion body myositis**. The study population comprises adult males and females aged over 40 years, with a weight range between 40 and 150 kg. Participants were selected based on their ability to provide informed consent and meet specific diagnostic criteria for inclusion body myositis, as defined by the ENMC IBM 2011 research diagnostic criteria. The trial includes both male and female subjects, and it is noted that the population includes vulnerable groups. Participants are required to adhere to local guidelines to minimize exposure to severe acute respiratory syndrome coronavirus 2 and must have a negative COVID-19 test result prior to the baseline. Lifestyle considerations include the ability to perform specific physical tasks, such as arising from a standard armchair and walking a short distance, which are necessary for completing the mTUG test. Additionally, participants must agree to use highly effective contraception and adhere to guidelines regarding contact with individuals suspected of having infectious diseases. The trial does not specify any particular dietary restrictions or habits beyond these considerations.

Plans and Procedures

The clinical trial is a **randomized**, **double-blind**, **placebo-controlled** study designed to evaluate the efficacy and safety of the investigational drug **Ulviprubart** in patients with **inclusion body myositis**. The trial is structured in multiple parts, with Part B focusing on the primary efficacy and safety objectives, and Part C assessing pharmacodynamic recovery. The study is expected to last until January 2026, with recruitment starting in November 2023. Participants will be involved for a maximum of 76 weeks, during which they will receive subcutaneous injections of Ulviprubart or placebo.

The sequence of study visits begins with a screening visit to confirm eligibility based on criteria such as age, weight, and diagnosis of inclusion body myositis. Baseline assessments will be conducted on Day 1, followed by regular follow-up visits to monitor efficacy and safety outcomes. The primary endpoint for Part B is the mean change from baseline in the IBM Functional Rating Scale at Week 76. Secondary endpoints include changes in muscle strength and the incidence of adverse events. The end-of-study visit will evaluate the recovery of KLRG1+ cells post-treatment.

Participants may be withdrawn from the study early if they experience severe adverse events, fail to adhere to the study protocol, or withdraw consent. The trial's design ensures that all participants, regardless of group assignment, receive comprehensive monitoring and care throughout the study duration. The study's rigorous methodology and adherence to ethical standards aim to provide reliable data on the potential benefits and risks of Ulviprubart in treating inclusion body myositis.

Treatment

The clinical trial involves the administration of **Ulviprubart**, an experimental medication, which is a **solution for injection**. Ulviprubart is a humanised afucosylated IgG1 monoclonal antibody that binds to the killer cell lectin-like receptor G1 (KLRG1). The pharmaceutical form is a solution intended for **subcutaneous injection**. The dosing regimen includes a maximum daily dose of 2 mg/kg and a total maximum dose of 20 mg/kg over a treatment period of 76 weeks. The administration of Ulviprubart is conducted under controlled conditions to ensure participant safety and compliance. Monitoring of participant compliance is achieved through regular assessments and documentation of dosing schedules.

The study also includes a **placebo** as a comparator treatment. The placebo is designed to match the test product in appearance and administration route, which is also a solution for injection. The placebo is administered subcutaneously, following the same dosing schedule as the experimental medication, to maintain the double-blind nature of the trial. The use of a placebo allows for the assessment of the efficacy and safety of Ulviprubart by providing a baseline for comparison. Compliance with the placebo administration is monitored similarly to the experimental treatment, ensuring the integrity of the trial data.

Efficacy

The efficacy of the investigational product, ABC008, in the treatment of **Inclusion Body Myositis (IBM)** will be assessed through a randomized, double-blind, placebo-controlled, multicenter study. The primary efficacy endpoint for Part B of the study is the mean change from Baseline (Day 1) in the IBM Functional Rating Scale (IBMFRS) at Week 76. This scale is a validated tool used to measure functional abilities in patients with IBM. Additionally, Part C of the study will evaluate pharmacodynamic (PD) recovery by assessing the time from the end of treatment to the recovery of killer cell lectin-like receptor G1 (KLRG1)+ cells.

Secondary efficacy endpoints include the mean change from Baseline (Day 1) in Manual Muscle Testing (MMT) 12 and hand grip strength by dynamometry at Week 76. These measurements will provide further insights into the functional and muscular improvements in subjects receiving the treatment. The collection and analysis of these efficacy parameters will be conducted at specified timepoints, with the primary focus on Week 76, to ensure a comprehensive evaluation of the treatment's impact over the study period.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Adult males and females age >40 years at the time of the first dose of study medication; 2. Able to read, understand, and provide signed informed consent prior to the performance of any study-related procedures; 3. Diagnosis of either clinico-pathologically defined IBM, clinically defined IBM, or probable IBM according to the ENMC IBM 2011 research diagnostic criteria Rose et al., 2013, modified to allow inclusion of subjects with age of onset ≥40 years documented IBM. Documented histopathology results must be available prior to Baseline (Day 1) to confirm eligibility. 4. Weight >40 and <150 kg; 5. Diagnosis of either clinico-pathologically defined IBM, clinically defined IBM, or probable IBM according to the ENMC IBM 2011 research diagnostic criteria modified to allow inclusion of subjects with age of onset ≥40 years (Rose et al., 2013). Documented histopathology results must be available prior to Baseline (Day 1) to confirm eligibility; 6. As required to complete the mTUG test, able to arise from a tandard armchair (described in Section 6.2.6, with use of their arms but without support from another person or device (e.g., cane, walking stick), at Screening and Baseline (Day 1); 7. As required to complete the mTUG test, able to walk three meters, turn around, walk back to the chair, and sit down, with or without an assistive device. Once arisen from the chair, subject may use any walking device but cannot be supported by another person, furniture, or a wall.; 8. Agree to adhere to relevant local guidelines regarding minimizing exposure to severe acute respiratory syndrome coronavirus 2 from the first Screening Visit until EOT/ETV; 9. Negative coronavirus disease 2019 (COVID-19) test results within 48 hours before Baseline (Day 1) (polymerase chain reaction [PCR] or rapid antigen testing as per local guidance); 10. Agree (to the best of their knowledge), to avoid contact with any person suspected or known to have an infectious disease of which they are at risk of contracting from the first Screening Visit until the EOT/ETV; 11. Women of childbearing potential (WOCBP) and male subjects with female partners who are WOCBP (based on gender assignation at birth) must agree to use highly effective (<1% failure rate) contraception (as detailed in protocol section 7.6.4) for at least 30 days prior to the first dose of study medication, during the study, and for 180 days following EOT/ETV; 12. Male subjects (based on gender assignation at birth) must refrain from sperm donation for the duration of the study and for 180 days after EOT/ETV; 13. WOCBP (based on gender assignation at birth) must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline (Day 1).

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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 three years, either before or after), myositis in overlap with another autoimmune disease (e.g., systemic lupus, systemic sclerosis, rheumatoid arthritis), or muscular dystrophy; 2. 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; 3. Presence of another autoimmune or autoinflammatory disease which, in the view of the Principal Investigator or MM, may impact the subject’s ability to perform study procedures such that it would confound clinical assessment. Examples include 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 4. Receipt of any of the following treatments within the following time frames before Screening (or as otherwise specified): a. Intravenous or intramuscular corticosteroids: four weeks; b. Oral prednisone (or prednisone equivalent) >7.5 mg/day at Screening; c. Use of nonbiologic immunosuppressants (e.g., cyclosporine, mycophenolate mofetil or sodium, azathioprine, methotrexate, sirolimus, Janus kinase inhibitors): 12 weeks; d. Intra-articular therapies, such as corticosteroids or hyaluronic acid preparations: four weeks; e. Intravenous, intramuscular, or SC immunoglobulin (IVIG, IMIG, or SCIG): 12 weeks; f. Cytokine, integrin, or activin antagonists or selective co-stimulation modulators, including but not limited to, interleukin (IL)-1, IL-6, IL-17, IL-12/23, IL-23, interferon, integrin, and tumor necrosis factor α antagonists, abatacept, bimagrumab: 12 weeks; g. Cell-depleting or modulating therapies (e.g., alemtuzumab, antithymocyte globulin, atacicept, belimumab, obinutuzumab, ocrelizumab, ofatumumab, rituximab, siplizumab): 12 months; h. Use of chemotherapeutic regimens or other cytotoxic therapies, e.g., cyclophosphamide, doxorubicin or hydroxyrubicin, vincristine, and prednisone; purine analogs, alkylating agents: 24 weeks; i. Other immunomodulatory biologics: 12 weeks or five half-lives, whichever is longer; j. Transfusion with blood, packed red blood cells, or platelets or treatment with plasmapheresis or plasma exchange: six weeks; k. Anabolic steroids: four weeks; l. Growth hormone: four weeks; m. Physiologic supplementation with testosterone permitted provided dose stable for four weeks before Screening and expected to stay stable during the study; n. Therapies associated with neuromuscular side effects including antimalarial drugs (e.g., chloroquine, hydroxychloroquine), colchicine, cholesterol-lowering drugs (e.g., statins) except if on stable dose for at least 12 weeks, and without impact on assessment of IBM progression; 5. Initiation of an exercise or a physical therapy regimen within four weeks of Screening. Any exercise or physical therapy regimen initiated prior to the Screening Visit must have been stable for at least four weeks prior to Screening; Please refer to protocol for a complete list of the exclusion criteria