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

• ClinicalTrials.gov Identifier: NCT04880031
• Recruitment Status: Recruiting
• First Posted: May 10, 2021
• Last Update Posted: January 5, 2024
• Sponsor: Boston Pharmaceuticals
• Information provided by (Responsible Party): Boston Pharmaceuticals

Tracking Information

• First Submitted Date: May 5, 2021
• First Posted Date: May 10, 2021
• Last Update Posted Date: January 5, 2024
• Actual Study Start Date: September 30, 2021
• Estimated Primary Completion Date: December 15, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 1, 2023)

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

Original Primary Outcome Measures (submitted: May 5, 2021)

• Number of participants with treatment emergent adverse events (TEAE) and treatment emergent serious adverse events (TESAE) [ Time Frame: Until End of study/Early Termination (Day 169 ± 7 days) ]
  The effects of BOS-580 on safety and tolerability will be assessed.
• Changes from Baseline to Week 12 (Day 85) in systolic and diastolic blood pressure (BP) [ Time Frame: Baseline, Week 12 (Day 85) ]
  The effects of BOS-580 on safety and tolerability will be assessed.
• Changes from Baseline to Week 12 (Day 85) in heart rate [ Time Frame: Baseline, Week 12 (Day 85) ]
  The effects of BOS-580 on safety and tolerability will be assessed.
• Number of participants with Grade 3-4 laboratory abnormalities at Week 12 (Day 85) [ Time Frame: Week 12 (Day 85) ]
  The effects of BOS-580 on safety and tolerability will be assessed.

Current Secondary Outcome Measures (submitted: May 1, 2023)

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

Original Secondary Outcome Measures (submitted: May 5, 2021)

• Maximum serum drug concentration (Cmax) for BOS-580 [ Time Frame: At Days 1, 15, 29, 43, 57, 85, Follow-up visit (Day 113), End of study/Early Termination (Day 169 ± 7 days) (Pre-dose), and Day 8 ]
  The pharmacokinetics (PK) of BOS-580 will be assessed.
• Minimum serum drug concentration (Cmin) for BOS-580 [ Time Frame: At Days 1, 15, 29, 43, 57, 85, Follow-up visit (Day 113), End of study/Early Termination (Day 169 ± 7 days) (Pre-dose), and Day 8 ]
  The PK of BOS-580 will be assessed.
• Average serum drug concentration (Cavg) for BOS-580 [ Time Frame: At Days 1, 15, 29, 43, 57, 85, Follow-up visit (Day 113), End of study/Early Termination (Day 169 ± 7 days) (Pre-dose), and Day 8 ]
  The PK of BOS-580 will be assessed.
• Time to reach maximum serum concentration (Tmax) for BOS-580 [ Time Frame: At Days 1, 15, 29, 43, 57, 85, Follow-up visit (Day 113), End of study/Early Termination (Day 169 ± 7 days) (Pre-dose), and Day 8 ]
  The PK of BOS-580 will be assessed.
• Area under the serum concentration-time curve (AUC) from time zero to time of last measurable concentration (AUClast) for BOS-580 [ Time Frame: At Days 1, 15, 29, 43, 57, 85, Follow-up visit (Day 113), End of study/Early Termination (Day 169 ± 7 days) (Pre-dose), and Day 8 ]
  The PK of BOS-580 will be assessed.
• Area under the serum concentration time curve during a dosage interval (AUCtau) for BOS-580 [ Time Frame: At Days 1, 15, 29, 43, 57, 85, Follow-up visit (Day 113), End of study/Early Termination (Day 169 ± 7 days) (Pre-dose), and Day 8 ]
  The PK of BOS-580 will be assessed.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of BOS-580 in Obese Subjects at Risk for, or With Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH)
• Official Title: A Phase 2a, Randomized, Blinded, Placebo-controlled Study of BOS-580 in Obese Subjects at Risk for, or With Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH)
• Brief Summary: This is a safety study to evaluate BOS-580 administered subcutaneously over 12 weeks in Part A or 24 weeks in Part B.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Nonalcoholic Steatohepatitis (NASH)

Intervention

• Drug: BOS-580
  BOS-580 will be administered by subcutaneous injection
• Drug: Placebo
  Placebo will be administered by subcutaneous injection

Study Arms

• Experimental: Cohort A1: BOS-580 Dose 1 or placebo (PBO)
  Interventions:

  • Drug: BOS-580
  • Drug: Placebo
• Experimental: Cohort A2: BOS-580 Dose 2 or PBO
  Interventions:

  • Drug: BOS-580
  • Drug: Placebo
• Experimental: Cohort A3: BOS-580 Dose 3 or PBO
  Interventions:

  • Drug: BOS-580
  • Drug: Placebo
• Experimental: Cohort A4: BOS-580 Dose 4 or PBO
  Interventions:

  • Drug: BOS-580
  • Drug: Placebo
• Experimental: Cohort A5: BOS-580 Dose 5 or PBO
  Interventions:

  • Drug: BOS-580
  • Drug: Placebo
• Experimental: Cohort B: BOS-580 Dose 1 or PBO
  Interventions:

  • Drug: BOS-580
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 1, 2023): 180
• Original Estimated Enrollment (submitted: May 5, 2021): 100
• Estimated Study Completion Date: December 15, 2024
• Estimated Primary Completion Date: December 15, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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, controlled attenuation parameter (CAP) score criteria and AST 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).
• History or presence of at least 2 of 4 components of metabolic syndrome: obesity/overweight, dyslipidemia (high triglycerides and/or low high density lipoprotein [HDL]), type 2 diabetes with elevated glycated hemoglobin (HbA1c), and hypertension.

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Medical Director; (617) 655-9681; clinicaltrials@bostonpharmaceuticals.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04880031
• Other Study ID Numbers: BOS-580-201
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Boston Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Boston Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Boston Pharmaceuticals
• Verification Date: June 2023