A Phase II/III Study of ABC008 to Determine Efficacy and Safety in IBM

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Abcuro Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

17 Jan 2024 → 27 Nov 2025

Decision date (initial)

2023-11-06

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Abcuro, Inc.

External identifiers

EU CT number

2022-501925-19-00

ClinicalTrials.gov

NCT05721573

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Others, Safety, Pharmacokinetic

Part A (Sentinel Cohort): NA for EU

Part B (Double-Blind Safety and Efficacy Cohort):
Primary Efficacy Objectives
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.
Safety Objectives
To determine the safety and tolerability of SC ABC008 in subjects with IBM.

Part C (PD Recovery Cohort):
To evaluate the PD recovery of the depletion of killer cell lectin-like receptor G1 (KLRG1)+ cells after the end of treatment with SC ABC008 in subjects with IBM.

Secondary objectives 1

1. Part B: Key Secondary Efficacy Objectives To determine the efficacy of SC ABC008 in subjects with IBM at W76, as measured using: 1. Manual Muscle Testing (MMT) 12; 2. Grip strength or the dominant hand by dynamometry; 3. Strength of quadriceps for the dominant leg by dynamometry; 4. Modified Timed Up and Go test (mTUG).

Conditions and MedDRA coding

inclusion body myositis

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Federal Agency For Medicines And Health Products, Paul-Ehrlich-Institut, European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. 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).

Exclusion criteria 1

1. 1. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. For Part B: The primary endpoint of the study will be mean change from Baseline (Day 1) in IBMFRS at W76. For Part C: The endpoint for Part C of the study will be PD recovery as assessed by the time from EOT/ETV to recovery of KLRG1+ cells.

Secondary endpoints 1

1. Efficacy: 1. Mean change from Baseline (Day 1) in MMT 12 at W76; 2. Mean change from Baseline (Day 1) in hand grip strength by dynamometry at W76; Safety: 1. Incidence, nature, and severity of TEAEs; 2. Incidence, nature, and severity of TESAEs; Please refer to protocol for a complete list of the efficacy and safety secondary Endpoints.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Abcuro Inc.

Sponsor organisation

Abcuro Inc.

Address

55 Chapel Street Suite 200

City

Newton

Postcode

02458-1070

Country

United States

Scientific contact point

Organisation

Abcuro Inc.

Contact name

Garry Weems

Public contact point

Organisation

Abcuro Inc.

Contact name

Armando Reyes

Third parties 10

Locations

3 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 41 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications