A Study of BOS-580 in Obese Subjects at Risk for, or With Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH)

Study Overview
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Brief Summary
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This is a safety study to evaluate BOS-580 administered subcutaneously over 12 weeks in Part A or 24 weeks in Part B.

Official Title
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A Phase 2a, Randomized, Blinded, Placebo-controlled Study of BOS-580 in Obese Subjects at Risk for, or With Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH)

Conditions
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Nonalcoholic Steatohepatitis (NASH)

Intervention / Treatment
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* Drug: BOS-580
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is either male or female and 18 to 75 years of age inclusive, at the time of signing the informed consent Obese participants with body mass index (BMI) of ≥ 27 kg/m^2 Hepatic fat fraction (HFF) measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) ≥8% Liver fibrosis assessment based on a vibration controlled transient elastography (VCTE) liver stiffness measurement (LSM) score of 7.0 to 9.9 kPa (Part A only) inclusive or 7.0 to 20.0 kPa (Part B only) inclusive and Liver injury assessment measured by aspartate aminotransferase (AST) >25U/L. A qualifying historical biopsy (confirmed eligibility based on the central pathology read) supersedes the LSM and controlled attenuation parameter (CAP) score criteria. Histopathologically confirmed F2 or F3 stage NASH on a diagnostic liver biopsy performed during Screening or within 6 months prior to the first day of dosing for historical biopsies (Part B only). Exclusion Criteria: Documented clinical, laboratory or radiologic evidence of cirrhosis (compensated or decompensated) Triglycerides ≥ 500 mg/dL Change in body weight (more than 5% self-reported OR 5 kg self-reported change during the previous 3 months from Screening, whichever is smaller) History of type 1 diabetes, diabetic ketoacidosis, or positive glutamic acid decarboxylase (GAD) auto-antibodies (latent autoimmune diabetes in adults) Hemoglobin A1c > 9.5% Subjects with a condition that requires substantial anticoagulant medication may not be eligible for the study enrollment (e.g., deep vein thrombosis).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A1: BOS-580 Dose 1 or placebo (PBO)<br> | Drug: BOS-580<br>* BOS-580 will be administered by subcutaneous injection<br>Drug: Placebo<br>* Placebo will be administered by subcutaneous injection<br>|
| Experimental: Cohort A2: BOS-580 Dose 2 or PBO<br> | Drug: BOS-580<br>* BOS-580 will be administered by subcutaneous injection<br>Drug: Placebo<br>* Placebo will be administered by subcutaneous injection<br>|
| Experimental: Cohort A3: BOS-580 Dose 3 or PBO<br> | Drug: BOS-580<br>* BOS-580 will be administered by subcutaneous injection<br>Drug: Placebo<br>* Placebo will be administered by subcutaneous injection<br>|
| Experimental: Cohort A4: BOS-580 Dose 4 or PBO<br> | Drug: BOS-580<br>* BOS-580 will be administered by subcutaneous injection<br>Drug: Placebo<br>* Placebo will be administered by subcutaneous injection<br>|
| Experimental: Cohort A5: BOS-580 Dose 5 or PBO<br> | Drug: BOS-580<br>* BOS-580 will be administered by subcutaneous injection<br>Drug: Placebo<br>* Placebo will be administered by subcutaneous injection<br>|
| Experimental: Cohort B: BOS-580 Dose 1 or PBO<br> | Drug: BOS-580<br>* BOS-580 will be administered by subcutaneous injection<br>Drug: Placebo<br>* Placebo will be administered by subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A and Part B: Number of participants with treatment-emergent adverse events (TEAE) and treatment-emergent serious adverse events (TESAE) | The effects of BOS-580 on safety and tolerability will be assessed. | Until End of study/Early Termination (Day 197) | 
| Part A and Part B: Changes from Baseline to Week 12 (Day 85) in systolic and diastolic blood pressure (BP) | The effects of BOS-580 on safety and tolerability will be assessed. | Baseline, Week 12 (Day 85) | 
| Part A and Part B: Changes from Baseline to Week 12 (Day 85) in heart rate | The effects of BOS-580 on safety and tolerability will be assessed. | Baseline, Week 12 (Day 85) | 
| Part A and Part B: Number of participants with Grade 3 and Grade 4 laboratory abnormalities at Week 12 (Day 85) | The effects of BOS-580 on safety and tolerability will be assessed. | Week 12 (Day 85) | 
| Part B only: Changes from Baseline to Week 24 (Day 169) and Week 28 (Day 197) in systolic and diastolic BP | The effects of BOS-580 on safety and tolerability will be assessed. | Baseline, Week 24 (Day 169), Week 28 (Day 197) | 
| Part B only: Changes from Baseline to Week 24 (Day 169) and Week 28 (Day 197) in heart rate | The effects of BOS-580 on safety and tolerability will be assessed. | Baseline, Week 24 (Day 169), Week 28 (Day 197) | 
| Part B only: Number of participants with Grade 3 and Grade 4 laboratory abnormalities at Week 24 (Day 169) and Week 28 (Day 197) | The effects of BOS-580 on safety and tolerability will be assessed. | Week 24 (Day 169) and Week 28 (Day 197) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A only: BOS-580 serum concentration on Day 8 of the first dose | The pharmacokinetics (PK) of BOS-580 will be assessed. | Day 8 | 
| Part A only: BOS-580 serum concentration at the end of the dosing interval (Ctrough) | The pharmacokinetics (PK) of BOS-580 will be assessed. | Pre-dose at Days 15, 29, 43, 57, 71, 85 and 113 (End of study/Early termination) for bi-weekly schedule; pre-dose on Days 29, 57, 85 and 113 (End of study/Early termination) for the monthly schedule | 
| Part B only: BOS-580 serum concentration on Day 7 | The PK of BOS-580 will be assessed. | Day 7 | 
| Part B only: BOS-580 serum concentration at the end of the dosing interval (Ctrough) | The PK of BOS-580 will be assessed. | Pre-dose at Days 29, 57, 85, 113, 141, 169 and at Day 196 (End of study/Early Termination) | 
| Part B Only: Area under the serum concentration-time curve (AUC) for BOS-580 for one dosing interval at steady state | The PK of BOS-580 will be assessed. | At Days 121, 127, 134 and pre-dose at Day 141 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BOS-580, Safety, Tolerability, Pharmacokinetics