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

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

This is a randomized, blinded, placebo-controlled study of Efimosfermin in obese participants at risk for, or with biopsy-confirmed, nonalcoholic steatohepatitis (NASH), with a single arm open-label extension. It includes Parts A, B, C and D.

Study Overview

• Status: Completed
• Conditions: Nonalcoholic Steatohepatitis (NASH)
• Intervention / Treatment: Drug: Placebo; Drug: Efimosfermin

• Study Type: Interventional
• Enrollment (Actual): 231
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Central Research Associates
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Arizona Liver Health
    • Peoria, Arizona, United States, 85381
      • Arizona Liver Health
    • Tucson, Arizona, United States, 85712
      • QLMC
    • Tucson, Arizona, United States, 85712
      • Arizona Liver Health
    • Tucson, Arizona, United States, 85712
      • Liver Institute PPLC
  • California
    • Canoga Park, California, United States, 91304
      • Alliance Research Institute
    • Fountain Valley, California, United States, 92708
      • ARK Clinical Research
    • Fresno, California, United States, 92720
      • Fresno Clinical Research Center
    • Montclair, California, United States, 91763
      • Catalina Research Institute
    • Orange, California, United States, 92868
      • Knowledge Research Center
    • Oxnard, California, United States, 93030
      • Fomat Medical Research
    • Rialto, California, United States, 92377
      • Inland Empire Clinical Trials
  • Florida
    • Fort Myers, Florida, United States, 33907
      • Southwest General Healthcare Center
    • Fort Myers, Florida, United States, 33912
      • Covenant Metabolic Specialists - Fort Myers
    • Hialeah Gardens, Florida, United States, 33016
      • Evolution Clinical Trials
    • Kendall, Florida, United States, 33176
      • Entrust Clinical Research Center
    • Lehigh Acres, Florida, United States, 33976
      • Galenus Group
    • Miami, Florida, United States, 33173
      • Century Research
    • Miami, Florida, United States, 33155
      • Miami Clinical Research
    • Miami, Florida, United States, 33126
      • G+C Research Group
    • Miami, Florida, United States, 33156
      • Advanced Clinical Research
    • Miami, Florida, United States, 33173
      • Admed Research
    • Miami Lakes, Florida, United States, 33014
      • Panex Clinical Research
    • Orlando, Florida, United States, 32803
      • Charter Research
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Sarasota, Florida, United States, 34240
      • Covenant Metabolic Specialists - Sarasota
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Kansas City Research Institute
  • North Carolina
    • Fayetteville, North Carolina, United States, 28304
      • Coastal Research Institute, LLC
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Lillestol Research LLC
  • Rhode Island
    • East Greenwich, Rhode Island, United States, 02818
      • Velocity Clinical Research
  • Texas
    • Austin, Texas, United States, 78745
      • Accelemed Research
    • Austin, Texas, United States, 78757
      • Pinnacle Clinical Research - Austin
    • Austin, Texas, United States, 78757
      • Texas Liver Institute - Austin
    • Bellaire, Texas, United States, 77401
      • Apex Mobile Clinical Research
    • Brownsville, Texas, United States, 78520
      • South Texas Research Institute-Brownsville
    • Edinburg, Texas, United States, 75839
      • South Texas Research Institute-Edinburg
    • Georgetown, Texas, United States, 78626
      • Pinnacle Clinical Research - Georgetown
    • Houston, Texas, United States, 77079
      • Houston Research Institute
    • Pearland, Texas, United States, 77584
      • LinQ Research, LLC
    • San Antonio, Texas, United States, 78229
      • Pinnacle Clinical Research - San Antonio
    • San Antonio, Texas, United States, 78215
      • American Research Corporation at Texas Liver Institute
    • San Antonio, Texas, United States, 78209
      • Quality Research, Inc
    • Waco, Texas, United States, 76710
      • Velocity Clinical Research - Waco
  • Utah
    • Salt Lake City, Utah, United States, 84117
      • Olympus Family Medicine
    • South Ogden, Utah, United States, 84405
      • South Ogden Family Medicine
  • Washington
    • Seattle, Washington, United States, 98105
      • Liver Institute Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria (Part A and Part B):

• 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.

Inclusion Criteria (Part C):

• Participant must have completed the Part B of the study.
• Participant willing to undergo liver biopsy at Week 56
• NASH F stage <F4 at 24 week assessment in Part B

Inclusion Criteria (Part D):

• BMI of ≥ 25 kg/m^2
• Liver fibrosis based on assessments taken during screening visit
• Participant should be willing and able to undergo liver biopsy during Screening (if a historical biopsy within 12 months prior to Screening is not available) and per protocol as judged by the Investigator.
• Other inclusion criteria may apply

Exclusion Criteria (Part A and Part B):

• 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%
• Participants with a condition that requires substantial anticoagulant medication may not be eligible for the study enrollment (e.g., deep vein thrombosis).

Exclusion Criteria (Part C):

• Participants that received their 24 week dose in Part B > 10 weeks prior to enrollment into Part C

Exclusion Criteria (Part D):

• Other causes of chronic liver disease
• Documented evidence or history of decompensated liver cirrhosis.
• History of type 1 diabetes or poorly controlled type 2 diabetes.
• History of malignancy.
• Use of other investigational drugs.
• Other exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A1: Efimosfermin Dose 1 or placebo (PBO)	Drug: Placebo; Placebo will be administered by subcutaneous injection; Drug: Efimosfermin; Efimosfermin will be administered by subcutaneous injection; Other Names: BOS-580
Experimental: Cohort A2: Efimosfermin Dose 2 or PBO	Drug: Placebo; Placebo will be administered by subcutaneous injection; Drug: Efimosfermin; Efimosfermin will be administered by subcutaneous injection; Other Names: BOS-580
Experimental: Cohort A3: Efimosfermin Dose 3 or PBO	Drug: Placebo; Placebo will be administered by subcutaneous injection; Drug: Efimosfermin; Efimosfermin will be administered by subcutaneous injection; Other Names: BOS-580
Experimental: Cohort A4: Efimosfermin Dose 4 or PBO	Drug: Placebo; Placebo will be administered by subcutaneous injection; Drug: Efimosfermin; Efimosfermin will be administered by subcutaneous injection; Other Names: BOS-580
Experimental: Cohort A5: Efimosfermin Dose 5 or PBO	Drug: Placebo; Placebo will be administered by subcutaneous injection; Drug: Efimosfermin; Efimosfermin will be administered by subcutaneous injection; Other Names: BOS-580
Experimental: Part B: Efimosfermin Dose 1 or PBO	Drug: Placebo; Placebo will be administered by subcutaneous injection; Drug: Efimosfermin; Efimosfermin will be administered by subcutaneous injection; Other Names: BOS-580
Experimental: Part C: Efimosfermin Dose 1	Drug: Efimosfermin; Efimosfermin will be administered by subcutaneous injection; Other Names: BOS-580
Experimental: Part D: Efimosfermin Dose 6 or PBO	Drug: Placebo; Placebo will be administered by subcutaneous injection; Drug: Efimosfermin; Efimosfermin will be administered by subcutaneous injection; Other Names: BOS-580
Experimental: Part D: Efimosfermin Dose 1 or PBO	Drug: Placebo; Placebo will be administered by subcutaneous injection; Drug: Efimosfermin; Efimosfermin will be administered by subcutaneous injection; Other Names: BOS-580

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A, Part B, Part C, and Part D: Number of participants with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)	The effects of Efimosfermin on safety and tolerability will be assessed.	Until End of study/Early Termination (Day 393)
Part A, Part B, Part C, and Part D: Changes from Baseline in systolic and diastolic blood pressure (BP)	The effects of Efimosfermin on safety and tolerability will be assessed.	Baseline, Week 12 (Day 85, Part A), Week 24 (Day 169, Part B), Week 56 (Day 393, Part C), and Weeks 36 (Day 253), and 48 (Day 337) (Part D)
Part A, Part B, Part C, and Part D: Changes from Baseline in heart rate	The effects of Efimosfermin on safety and tolerability will be assessed.	Baseline, Week 12 (Day 85, Part A), Week 24 (Day 169, Part B), Week 56 (Day 393, Part C), and Weeks 36 (Day 253), and 48 (Day 337) (Part D)
Part A, Part B, Part C, and Part D: Number of participants with Grade 3 and Grade 4 laboratory abnormalities	The effects of Efimosfermin on safety and tolerability will be assessed.	Baseline, Week 12 (Day 85, Part A), Week 24 (Day 169, Part B), Week 56 (Day 393, Part C), and Weeks 36 (Day 253), and 48 (Day 337) (Part D)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A only: Efimosfermin serum concentration on Day 8 of the first dose	The pharmacokinetics (PK) of Efimosfermin will be assessed.	Day 8
Part A only: Efimosfermin serum concentration at the end of the dosing interval (Ctrough)	The PK of Efimosfermin 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: Efimosfermin serum concentration on Day 7	The PK of Efimosfermin will be assessed.	Day 7
Part B and Part C: Efimosfermin serum concentration at the end of the dosing interval (Ctrough)	The PK of Efimosfermin will be assessed.	Pre-dose at Days 29, 57, 85, 113, 141, 169, 225, 253, 281, 309, 316, 323, 330, 337, 365 and at Day 393 (End of study/Early Termination)
Part B and Part C: Area under the serum concentration-time curve (AUC) for Efimosfermin for one dosing interval at steady state	The PK of Efimosfermin will be assessed.	At Days 121, 127, 134, 316, 323, 330 and pre-dose at Days 141 and 337

Collaborators and Investigators

• Sponsor: Boston Pharmaceuticals
• Collaborators: GSK Research and Development Limited

Publications and helpful links

General Publications

• Loomba R, Kowdley KV, Rodriguez J, Kim NJ, Alvarez AM, Morrow L, Jeglinski B, Clawson A, Chowdhury S, Bain G, Odrljin T. Efimosfermin alfa (BOS-580), a long-acting FGF21 analogue, in participants with phenotypic metabolic dysfunction-associated steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2a trial. Lancet Gastroenterol Hepatol. 2025 Aug;10(8):734-745. doi: 10.1016/S2468-1253(25)00067-6. Epub 2025 Jun 6.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2021
• Primary Completion (Actual): October 27, 2025
• Study Completion (Actual): October 27, 2025

Study Registration Dates

• First Submitted: May 5, 2021
• First Submitted That Met QC Criteria: May 5, 2021
• First Posted (Actual): May 10, 2021

Study Record Updates

• Last Update Posted (Estimated): October 30, 2025
• Last Update Submitted That Met QC Criteria: October 29, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Tolerability; BOS-580; Efimosfermin
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: 301182 (BOS-580-201)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No