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

NCT04880031 | Completed Phase 2 FDA Drug

• 1 other identifier: 301182 (BOS-580-201)
• Study Type: interventional
• Target: 231
• Locations: 1 country
• Sites: 48

Brief Summary

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.

Conditions

Nonalcoholic Steatohepatitis (NASH)

Keywords

BOS-580; Safety; Tolerability; Pharmacokinetics; Efimosfermin

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (5)

• Part A only: Efimosfermin serum concentration on Day 8 of the first dose

  Day 8

• Part A only: Efimosfermin serum concentration at the end of the dosing interval (Ctrough)

  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

  Day 7

• Part B and Part C: Efimosfermin serum concentration at the end of the dosing interval (Ctrough)

  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

  At Days 121, 127, 134, 316, 323, 330 and pre-dose at Days 141 and 337

Study Arms (9)

Cohort A1: Efimosfermin Dose 1 or placebo (PBO)

EXPERIMENTAL

Drug: Efimosfermin; Drug: Placebo

Cohort A2: Efimosfermin Dose 2 or PBO

EXPERIMENTAL

Drug: Efimosfermin; Drug: Placebo

Cohort A3: Efimosfermin Dose 3 or PBO

EXPERIMENTAL

Drug: Efimosfermin; Drug: Placebo

Cohort A4: Efimosfermin Dose 4 or PBO

EXPERIMENTAL

Drug: Efimosfermin; Drug: Placebo

Cohort A5: Efimosfermin Dose 5 or PBO

EXPERIMENTAL

Drug: Efimosfermin; Drug: Placebo

Part B: Efimosfermin Dose 1 or PBO

EXPERIMENTAL

Drug: Efimosfermin; Drug: Placebo

Part C: Efimosfermin Dose 1

EXPERIMENTAL

Drug: Efimosfermin

Part D: Efimosfermin Dose 6 or PBO

EXPERIMENTAL

Drug: Efimosfermin; Drug: Placebo

Part D: Efimosfermin Dose 1 or PBO

EXPERIMENTAL

Drug: Efimosfermin; Drug: Placebo

Interventions

Efimosfermin DRUG

Efimosfermin will be administered by subcutaneous injection

Also known as: BOS-580

Cohort A1: Efimosfermin Dose 1 or placebo (PBO); Cohort A2: Efimosfermin Dose 2 or PBO; Cohort A3: Efimosfermin Dose 3 or PBO; Cohort A4: Efimosfermin Dose 4 or PBO; Cohort A5: Efimosfermin Dose 5 or PBO; Part B: Efimosfermin Dose 1 or PBO; Part C: Efimosfermin Dose 1; Part D: Efimosfermin Dose 1 or PBO; Part D: Efimosfermin Dose 6 or PBO

Placebo DRUG

Placebo will be administered by subcutaneous injection

Cohort A1: Efimosfermin Dose 1 or placebo (PBO); Cohort A2: Efimosfermin Dose 2 or PBO; Cohort A3: Efimosfermin Dose 3 or PBO; Cohort A4: Efimosfermin Dose 4 or PBO; Cohort A5: Efimosfermin Dose 5 or PBO; Part B: Efimosfermin Dose 1 or PBO; Part D: Efimosfermin Dose 1 or PBO; Part D: Efimosfermin Dose 6 or PBO

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Boston Pharmaceuticals: lead
• GSK Research and Development Limited: collaborator

Study Sites (48)

Central Research Associates

Birmingham, Alabama, 35205, United States

Location

Arizona Liver Health

Chandler, Arizona, 85224, United States

Location

Arizona Liver Health

Peoria, Arizona, 85381, United States

Location

Arizona Liver Health

Tucson, Arizona, 85712, United States

Location

Liver Institute PPLC

Tucson, Arizona, 85712, United States

Location

QLMC

Tucson, Arizona, 85712, United States

Location

Alliance Research Institute

Canoga Park, California, 91304, United States

Location

Ark Clinical Research

Fountain Valley, California, 92708, United States

Location

Fresno Clinical Research Center

Fresno, California, 92720, United States

Location

Catalina Research Institute

Montclair, California, 91763, United States

Location

Knowledge Research Center

Orange, California, 92868, United States

Location

FOMAT Medical Research

Oxnard, California, 93030, United States

Location

Inland Empire Clinical Trials

Rialto, California, 92377, United States

Location

Southwest General Healthcare Center

Fort Myers, Florida, 33907, United States

Location

Covenant Metabolic Specialists - Fort Myers

Fort Myers, Florida, 33912, United States

Location

Evolution Clinical Trials

Hialeah Gardens, Florida, 33016, United States

Location

Entrust Clinical Research Center

Kendall, Florida, 33176, United States

Location

Galenus Group

Lehigh Acres, Florida, 33976, United States

Location

G+C Research Group

Miami, Florida, 33126, United States

Location

Miami Clinical Research

Miami, Florida, 33155, United States

Location

Advanced Clinical Research

Miami, Florida, 33156, United States

Location

Admed Research

Miami, Florida, 33173, United States

Location

Century Research

Miami, Florida, 33173, United States

Location

Panex Clinical Research

Miami Lakes, Florida, 33014, United States

Location

Charter Research

Orlando, Florida, 32803, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

Covenant Metabolic Specialists - Sarasota

Sarasota, Florida, 34240, United States

Location

Tandem Clinical Research

Marrero, Louisiana, 70072, United States

Location

Kansas City Research Institute

Kansas City, Missouri, 64131, United States

Location

Coastal Research Institute, LLC

Fayetteville, North Carolina, 28304, United States

Location

Lillestol Research LLC

Fargo, North Dakota, 58104, United States

Location

Velocity Clinical Research

East Greenwich, Rhode Island, 02818, United States

Location

Accelemed Research

Austin, Texas, 78745, United States

Location

Pinnacle Clinical Research - Austin

Austin, Texas, 78757, United States

Location

Texas Liver Institute - Austin

Austin, Texas, 78757, United States

Location

Apex Mobile Clinical Research

Bellaire, Texas, 77401, United States

Location

South Texas Research Institute-Brownsville

Brownsville, Texas, 78520, United States

Location

South Texas Research Institute-Edinburg

Edinburg, Texas, 75839, United States

Location

Pinnacle Clinical Research - Georgetown

Georgetown, Texas, 78626, United States

Location

Houston Research Institute

Houston, Texas, 77079, United States

Location

LinQ Research, LLC

Pearland, Texas, 77584, United States

Location

Quality Research, Inc

San Antonio, Texas, 78209, United States

Location

American Research Corporation at Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

Pinnacle Clinical Research - San Antonio

San Antonio, Texas, 78229, United States

Location

Velocity Clinical Research - Waco

Waco, Texas, 76710, United States

Location

Olympus Family Medicine

Salt Lake City, Utah, 84117, United States

Location

South Ogden Family Medicine

South Ogden, Utah, 84405, United States

Location

Liver Institute NorthWest

Seattle, Washington, 98105, United States

Location

Related Publications (1)

• 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.

  PMID: 40484014 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Part C - Open Label; Part D - Open Label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2021
• First Posted: May 10, 2021
• Study Start: September 30, 2021
• Primary Completion: October 27, 2025
• Study Completion: October 27, 2025
• Last Updated: October 30, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (48)