A Pivotal Clinical Study to Investigate Efimosfermin Alfa in Participants With Biopsy-confirmed F2- or F3-stage MASH

NCT07221227 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: 3011602025-523675-39
• Study Type: interventional
• Target: 1,200
• Locations: 9 countries
• Sites: 91

Brief Summary

The purpose of this study is to assess the safety and efficacy of efimosfermin alfa in the resolution of steatohepatitis and improvement of liver-related clinical outcome compared to placebo in individuals with MASH and biopsy-confirmed F2- or F3-stage fibrosis.

Conditions

Non-alcoholic Fatty Liver Disease

Keywords

Efimosfermin Alfa; Metabolic Dysfunction-Associated Steatohepatitis; Non-alcoholic Fatty Liver Disease; ZENITH-1

Outcome Measures

Primary Outcomes (3)

• Proportion of participants experiencing improvement in fibrosis by >=1 stage and no worsening of steatohepatitis at Week 52

  Proportion of participants experiencing improvement in fibrosis of greater than or equal to (\>=) 1 stage by MASH clinical research network (CRN) fibrosis scores and no worsening of steatohepatitis (defined as no increase in nonalcoholic fatty liver disease activity score \[NAS\] for ballooning, inflammation, or steatosis) at 52 weeks will be assessed. MASH CRN fibrosis score ranges from 0 to 4, higher score indicates greater severity. NAS score ranges from 0 to 8, higher score indicates worse disease activity.

  At Week 52

• Proportion of participants experiencing resolution of steatohepatitis reading and no worsening of MASH CRN fibrosis score at Week 52

  Resolution of steatohepatitis is defined as absence of fatty liver disease or isolated or simple steatosis without steatohepatitis and a NAS of 0 or 1 for inflammation, 0 for ballooning, and any value for steatosis. NAS score ranges from 0 to 8, higher score indicates worse disease activity. MASH CRN fibrosis score ranges from 0 to 4, higher score indicates greater severity.

  At Week 52

• Time from randomization to an adjudicated composite liver-related clinical outcome

  Liver-related outcome will comprised of all-cause mortality; transplantation; occurrence of significant hepatic events.

  From Randomization (Day 1) to 48 months

Secondary Outcomes (32)

• Number of participants with treatment-emergent adverse events (TEAEs) and TEAEs by severity

  At Week 52 and at Month 48

• Number of participants with TEAEs leading to discontinuation and TEAEs leading to discontinuation by severity

  At Week 52 and at Month 48

• Number of participants with Grade 3 and Grade 4 laboratory abnormalities

  At Week 52 and at Month 48

• Proportion of participants experiencing resolution of steatohepatitis on overall histopathological reading and improvement in liver fibrosis of >=1 stage at Week 52

  At Week 52

• Proportion of participants experiencing improvement in fibrosis by >=1 stage and no worsening of Steatohepatitis at Month 48

  At Month 48

Study Arms (3)

Participants receiving dose level 1 of efimosfermin alfa

EXPERIMENTAL

Drug: Efimosfermin alfa

Participants receiving dose level 2 of efimosfermin alfa

EXPERIMENTAL

Drug: Efimosfermin alfa

Participants receiving Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Efimosfermin alfa DRUG

Efimosfermin alfa will be administered

Participants receiving dose level 1 of efimosfermin alfa

Placebo DRUG

Placebo will be administered

Participants receiving Placebo

Eligibility Criteria

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

You may qualify if:

• Able and willing to understand and sign a written informed consent form that must be obtained prior to the initiation of study procedures
• Age \>=18 and \<=75 years at enrollment
• History or presence of 2 or more of the 5 components of metabolic syndrome per American Heart Association definition
• Liver biopsy confirmation of MASH consistent with stage F2 or F3 fibrosis and a NAS score \>=4 confirmed by a central pathologist

You may not qualify if:

• Contraindication or ineligibility for percutaneous liver biopsy
• ALT or AST \>=5 x upper limit of normal (ULN)
• Total bilirubin \>=1.3 milligram per deciliter (mg/dL). Individuals with documented Gilbert's syndrome may be enrolled if they experienced an isolated increase in total bilirubin of \>=1.3 mg/dL and direct bilirubin is \<=20% of total bilirubin; otherwise, the individual will be excluded.
• Serum albumin \<=3.5 grams per deciliter (g/dL)
• International normalized ratio (INR) \>=1.3 not due to therapeutic anticoagulation. Individuals receiving chronic anticoagulant treatment with higher INR values may be enrolled at the discretion of the Investigator and Study Medical Monitor.
• Alkaline phosphatase (ALP) \>=2\*ULN
• Platelet (PLT) count \<140,000 per (/) cubic millimeter (mm\^3); individuals with a PLT count between 110,000/mm\^3 and 140,000/mm\^3 may be enrolled after discussion with the Study Medical Monitor.
• Serum creatinine \>=1.5 mg/dL or creatinine clearance \<=60 milliliter (mL)/minute (min)/1.73 square meter by Chronic Kidney Disease Epidemiology Collaboration equation
• Alpha-fetoprotein \>=20 nanogram per milliliter (ng/mL)
• Glycated hemoglobin \>=9.0%
• Model for End-Stage Liver Disease score \>=12 unless the score is elevated in the absence of liver dysfunction (e.g., Gilbert's syndrome)
• Phosphatidyl ethanol (PEth) \>=80 ng/mL at Screening
• Evidence of infection with any of the following:
• Human immunodeficiency virus;
• Hepatitis B virus (detectable HBsAg at Screening);

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (91)

GSK Investigational Site

Chandler, Arizona, 85224, United States

RECRUITING

GSK Investigational Site

Tucson, Arizona, 85712, United States

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GSK Investigational Site

Little Rock, Arkansas, 72211, United States

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GSK Investigational Site

Arcadia, California, 91006, United States

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GSK Investigational Site

Covina, California, 91723, United States

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GSK Investigational Site

Folsom, California, 95630, United States

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GSK Investigational Site

Los Angeles, California, 90057, United States

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GSK Investigational Site

Montclair, California, 91763, United States

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GSK Investigational Site

Riverdale, California, 30274, United States

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GSK Investigational Site

San Diego, California, 92120, United States

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GSK Investigational Site

Santa Maria, California, 93458, United States

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GSK Investigational Site

Van Nuys, California, 91405, United States

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GSK Investigational Site

Colorado Springs, Colorado, 80907, United States

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GSK Investigational Site

Boynton Beach, Florida, 33435, United States

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GSK Investigational Site

Cape Coral, Florida, 33914, United States

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GSK Investigational Site

Clermont, Florida, 34711, United States

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GSK Investigational Site

Fort Myers, Florida, 33912, United States

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GSK Investigational Site

Hialeah, Florida, 33016, United States

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GSK Investigational Site

Hialeah, Florida, 33016, United States

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GSK Investigational Site

Homestead, Florida, 33033, United States

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GSK Investigational Site

Inverness, Florida, 34452, United States

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GSK Investigational Site

Jacksonville, Florida, 32216, United States

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GSK Investigational Site

Kissimmee, Florida, 34744, United States

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GSK Investigational Site

Lakeland, Florida, 33803, United States

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GSK Investigational Site

Maitland, Florida, 32751, United States

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GSK Investigational Site

Miami, Florida, 33135, United States

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GSK Investigational Site

Miami, Florida, 33144, United States

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GSK Investigational Site

Miami, Florida, 33155, United States

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GSK Investigational Site

Miami, Florida, 33156, United States

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GSK Investigational Site

Miami, Florida, 33173, United States

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GSK Investigational Site

Miami, Florida, 33176, United States

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GSK Investigational Site

Miami, Florida, 33184, United States

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GSK Investigational Site

Miami Lakes, Florida, 33014, United States

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GSK Investigational Site

Ocala, Florida, 34471, United States

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GSK Investigational Site

Palmetto Bay, Florida, 33157, United States

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GSK Investigational Site

Sarasota, Florida, 34201, United States

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GSK Investigational Site

Marietta, Georgia, 30060, United States

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GSK Investigational Site

Topeka, Kansas, 66606, United States

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GSK Investigational Site

Bastrop, Louisiana, 71220, United States

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GSK Investigational Site

Marrero, Louisiana, 70072, United States

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GSK Investigational Site

Kansas City, Missouri, 64131, United States

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GSK Investigational Site

Springfield, Missouri, 62703, United States

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GSK Investigational Site

St Louis, Missouri, 63141, United States

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GSK Investigational Site

Las Vegas, Nevada, 89106, United States

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GSK Investigational Site

East Syracuse, New York, 13057, United States

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GSK Investigational Site

New York, New York, 10036, United States

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GSK Investigational Site

New York, New York, 10036, United States

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GSK Investigational Site

Fayetteville, North Carolina, 28304, United States

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GSK Investigational Site

Morehead City, North Carolina, 28557, United States

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GSK Investigational Site

Akron, Ohio, 44320, United States

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GSK Investigational Site

Springboro, Ohio, 45066, United States

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GSK Investigational Site

Westlake, Ohio, 44145, United States

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GSK Investigational Site

Chattanooga, Tennessee, 37421, United States

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GSK Investigational Site

Arlington, Texas, 76012, United States

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GSK Investigational Site

Austin, Texas, 78704, United States

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GSK Investigational Site

Austin, Texas, 78757, United States

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GSK Investigational Site

Austin, Texas, 78759, United States

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GSK Investigational Site

Bellaire, Texas, 77401, United States

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GSK Investigational Site

Brownsville, Texas, 78526, United States

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GSK Investigational Site

Dallas, Texas, 75243, United States

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GSK Investigational Site

DeSoto, Texas, 75115, United States

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GSK Investigational Site

Houston, Texas, 77004, United States

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GSK Investigational Site

Irving, Texas, 75061, United States

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GSK Investigational Site

Richmond, Texas, 77406, United States

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GSK Investigational Site

San Antonio, Texas, 78209, United States

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GSK Investigational Site

San Antonio, Texas, 78215, United States

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GSK Investigational Site

San Antonio, Texas, 78229, United States

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GSK Investigational Site

Seabrook, Texas, 77586, United States

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GSK Investigational Site

Sugar Land, Texas, 77479, United States

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GSK Investigational Site

Tomball, Texas, 77375, United States

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GSK Investigational Site

Waco, Texas, 76710, United States

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GSK Investigational Site

Waco, Texas, 76712, United States

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GSK Investigational Site

West Jordan, Utah, 84088, United States

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GSK Investigational Site

Manassas, Virginia, 20110, United States

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GSK Investigational Site

Norfolk, Virginia, 23502, United States

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GSK Investigational Site

Seattle, Washington, 98105, United States

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GSK Investigational Site

Broadmeadow, New South Wales, 2292, Australia

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GSK Investigational Site

Heidelberg, Victoria, 3084, Australia

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GSK Investigational Site

Québec, Quebec, G1N 4V3, Canada

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GSK Investigational Site

Pokfulam, Hong Kong

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GSK Investigational Site

Gifu, 503-8502, Japan

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GSK Investigational Site

Kanagawa, 215-0026, Japan

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GSK Investigational Site

Kyoto, 602-8566, Japan

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GSK Investigational Site

Musashino, 180-8610, Japan

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GSK Investigational Site

Yokohama, 236-0004, Japan

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GSK Investigational Site

Wellington, 6021, New Zealand

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GSK Investigational Site

San Juan, 00927, Puerto Rico

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GSK Investigational Site

Riyadh, 11472, Saudi Arabia

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GSK Investigational Site

Chiayi City, 600, Taiwan

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GSK Investigational Site

Kaohsiung City, 80756, Taiwan

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GSK Investigational Site

Kaohsiung City, 83301, Taiwan

RECRUITING

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Central Study Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718; GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double blind study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2025
• First Posted: October 27, 2025
• Study Start: October 24, 2025
• Primary Completion (Estimated): March 29, 2028
• Study Completion (Estimated): December 12, 2031
• Last Updated: July 27, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.

Locations

AU (2); CA (1); PR (1); HK (1); NZ (1); TW (3); JP (5); SA (1); US (76)