A Phase 1 Study of ABC008 in Ascending (Single Ascending Dose/Multiple Ascending Dose) Study in Patients With (IBM)

Study Overview
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Brief Summary
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An open-label, ascending dose study for adult patients with Inclusion Body Myositis (IBM).

Official Title
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A Phase 1, Open-Label, Ascending Dose Study of ABC008 in Adult Patients With Inclusion Body Myositis (IBM)

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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Key Inclusion Criteria: Diagnosis of either clinico-pathologically defined IBM, clinically defined IBM, or probable IBM according to the European Neuromuscular Center (ENMC) IBM 2011 Able to arise from a chair (with or without armrests) without support from another person or device Able to ambulate at least 20 feet / 6 meters with or without assistive device Exclusion Criteria: Taking > 7.5 mg prednisolone (or equivalent) or on intravenous immunoglobulin (IVIg) or other immunosuppressants within the last 3 months. Topical, nasal, and ocular corticosteroids are allowed unless they are being widely applied or the severity of the underlying condition makes them unsuitable in the Investigator's opinion. Local steroid injections are allowed

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort D1<br>Single Dose 0.1 mg / kg ABC008 | Drug: ABC008<br>* ABC008<br>|
| Experimental: Cohort D2<br>Single Dose 0.5 mg / kg ABC008 | Drug: ABC008<br>* ABC008<br>|
| Experimental: Cohort D3<br>Single Dose 2.0 mg / kg ABC008 | Drug: ABC008<br>* ABC008<br>|
| Experimental: Cohort D4<br>Single Dose 5.0 mg / kg ABC008 | Drug: ABC008<br>* ABC008<br>|
| Experimental: Cohort D5<br>X.X mg / kg ABC008 | Drug: ABC008<br>* ABC008<br>|
| Experimental: Cohort 6<br>Single 2.0 mg / kg ABC008 | Drug: ABC008<br>* ABC008<br>|
| Experimental: MAD Phase Cohort 1<br>Multiple Dose 0.1 mg / kg ABC008 every 8 weeks | Drug: ABC008<br>* ABC008<br>|
| Experimental: MAD Phase Cohort 2<br>Multiple Dose 0.5 mg / kg ABC008 every 8 weeks | Drug: ABC008<br>* ABC008<br>|
| Experimental: MAD Phase Cohort 3<br>Multiple Dose 2.0 mg / kg ABC008 every 8 weeks | Drug: ABC008<br>* ABC008<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Safety and Tolerability | Characterize the safety and tolerability profile of single (SAD) and multiple (MAD) escalating dose levels of ABC008 in IBM when administered subcutaneously (SC) as measured by the number and severity of treatment emergent adverse events, serious adverse events, and adverse events of special interest, number of dose limiting toxicities. | Through Study Completion an average of 28 weeks for SAD (Single Ascending Dose) phase and 52 weeks for MAD (Multiple Ascending Dose) phase] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of peak serum concentration (Cmax) | Assess the peak serum concentration (Cmax) of a single dose of ABC008 | Day 1 and throughout the 24 weeks of follow up | 
| Assessment of time to peak serum concentration (Tmax) | Assess the time to peak serum concentration (Tmax) of a single dose of ABC008 | Day 1 and throughout the 24 weeks of follow up | 
| Assessment of terminal half-life (t½) | Assess the terminal half-life (t½) of ABC008 | Day 1 | 
| Assessment of area under the concentration versus time curve from time zero to 24 hours post-dose (AUC0-24hr) | Assess the area under the concentration versus time curve of a single dose of ABC008 from time zero to 24 hours post-dose (AUC0-24hr) | Day 1 | 
| Assessment of apparent clearance (CL/F) | Assessment of apparent clearance (CL/F) of a single dose of ABC008 | Day 1 and throughout the 24 weeks of follow up | 
| Assessment of apparent volume of distribution (Vz/F) | Assessment of apparent volume of distribution (Vz/F) of a single dose of ABC008 | Day 1 and throughout the 24 weeks of follow up | 
| Characterization of changes in KLRG1 expressing lymphocytes | Characterize changes in KLRG1 expressing lymphocytes | Day 1 and throughout the 24 weeks of follow up | 
| Qualitative assessment of [ 89Zr]Zr-Df-crefmirlimab | Qualitative assessment of [ 89Zr]Zr-Df-crefmirlimab uptake in involved skeletal muscles including inflamed and non-inflamed sites as determined by using a visual scoring (VS) system for the time point assessed, the possible scores VS1-VS5 | [Through Study Completion, avg. 48 weeks | 
| Assessment of global distribution of [ 89Zr]Zr-Df-crefmirlimab uptake in skeletal muscle | Assessment of global distribution of [ 89Zr]Zr-Df-crefmirlimab uptake in skeletal muscle; Pattern(s) of absolute and relative changes in uptake within various skeletal muscle groups; Homogenous/diffuse, Focal, Mixed, Other | [Through Study Completion, avg. 48 weeks | 
| Assessment of global distribution of [ 89Zr]Zr-Df-crefmirlimab uptake in lymphoid organs | Assessment of global distribution of [ 89Zr]Zr-Df-crefmirlimab uptake in lymphoid organs; Uptake and relative changes in uptake within lymphoid tissue including spleen and lymph nodes as well as other T-cell rich tissues such as bone marrow | [Through Study Completion, avg. 48 weeks | 
| Quantitative assessment of [ 89Zr]Zr-Df-crefmirlimab pre and post dosing of ABC008 | Quantitative assessment of [ 89Zr]Zr-Df-crefmirlimab uptake and relative changes in uptake within inflamed muscle tissue through Positron Emission Tomography (PET)/computed tomography (CT) imaging pre- and post-dosing with ABC008 | [Through Study Completion, avg. 48 weeks | 
| Quantitative assessment of [ 89Zr]Zr-Df-crefmirlimab, determined by standardized uptake value (SUV)-based quantitative analysis peak (SUVpeak) | Quantitative assessment of [ 89Zr]Zr-Df-crefmirlimab uptake in involved skeletal muscles including inflamed and non-inflamed sites, and measurement of magnitude of difference observations as determined by standardized uptake value (SUV)-based quantitative analysis peak (SUVpeak) | [Through Study Completion, avg. 48 weeks | 
| Quantitative assessment of [ 89Zr]Zr-Df-crefmirlimab, determined by standardized uptake value (SUV)-based quantitative analysis mean (SUVmean) | Quantitative assessment of [ 89Zr]Zr-Df-crefmirlimab uptake in involved skeletal muscles including inflamed and non-inflamed sites, and measurement of magnitude of difference observations as determined by standardized uptake value (SUV)-based quantitative analysis mean (SUVmean) | [Through Study Completion, avg. 48 weeks | 
| Quantitative assessment of [ 89Zr]Zr-Df-crefmirlimab, determined by standardized uptake value (SUV)-based quantitative analysis SUV of diseased muscle | Quantitative assessment of [ 89Zr]Zr-Df-crefmirlimab uptake in involved skeletal muscles including inflamed and non-inflamed sites, and measurement of magnitude of difference observations as determined by standardized uptake value (SUV)-based quantitative analysis SUV of diseased muscle | [Through Study Completion, avg. 48 weeks | 
| Quantitative assessment of [ 89Zr]Zr-Df-crefmirlimab, determined by standardized uptake value (SUV)-based quantitative analysis SUV reference tissue | Quantitative assessment of [ 89Zr]Zr-Df-crefmirlimab uptake in involved skeletal muscles including inflamed and non-inflamed sites, and measurement of magnitude of difference observations as determined by standardized uptake value (SUV)-based quantitative analysis SUV reference tissue | [Through Study Completion, avg. 48 weeks | 
| Quantitative assessment of [ 89Zr]Zr-Df-crefmirlimab, determined by standardized uptake value (SUV)-based quantitative analysis maximum (SUVmax) | Quantitative assessment of [ 89Zr]Zr-Df-crefmirlimab uptake in involved skeletal muscles including inflamed and non-inflamed sites, and measurement of magnitude of difference observations as determined by standardized uptake value (SUV)-based quantitative analysis maximum (SUVmax) | [Through Study Completion, avg. 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inclusion Body Myositis, IBM