A Clinical Study to Investigate the Safety and Tolerability of Efimosfermin Alfa Injection in Participants With Known or Suspected F2- or F3-stage MASH

NCT07221188 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: 3062462025-523674-16
• Study Type: interventional
• Target: 1,250
• Locations: 1 country
• Sites: 43

Brief Summary

This study will evaluate the safety and tolerability of Efimosfermin Alfa for participants with known or suspected MASH with fibrosis consistent with stage F2 or F3.

Conditions

Non-alcoholic Fatty Liver Disease

Keywords

Metabolic Dysfunction-Associated Steatohepatitis; efimosfermin alfa; Safety; Tolerability; Phase 3; ZENITH-2

Outcome Measures

Primary Outcomes (3)

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

  At Week 52

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

  At Week 52

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

  At Week 52

Secondary Outcomes (21)

• Absolute Change from Baseline in enhanced liver fibrosis (ELF) score

  Baseline (Day 1) and up to Week 52

• Percent Change from Baseline in ELF score

  Baseline (Day 1) and up to Week 52

• Number of participants achieving an improvement in ELF score greater than equal to 0.5

  At Week 52

• Absolute Change from Baseline in vibration-controlled transient elastography (VCTE)- liver stiffness measurement (LSM) scores

  Baseline (Day 1) and up to Week 52

• Percent Change from Baseline in VCTE- LSM scores

  Baseline (Day 1) and up to Week 52

Study Arms (3)

Efimosfermin Alfa Dose Level 1

EXPERIMENTAL

Participants randomized to this group will receive Efimosfermin Alfa at dose level 1

Drug: Efimosfermin Alfa

Efimosfermin Alfa Dose Level 2

EXPERIMENTAL

Participants randomized to this group will receive Efimosfermin Alfa at dose level 2

Drug: Efimosfermin Alfa

Placebo

PLACEBO COMPARATOR

Participants randomized to this group will receive Placebo

Drug: Placebo

Interventions

Efimosfermin Alfa DRUG

Efimosfermin Alfa will be administered

Efimosfermin Alfa Dose Level 1; Efimosfermin Alfa Dose Level 2

Placebo DRUG

Placebo will be administered

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 (ICF) that must be obtained prior to the initiation of study procedures
• Age \>=18 through \<=75 years at enrolment
• History or presence of 2 or more of the 5 components of metabolic syndrome per American Heart Association definition
• History or presence of known or suspected MASH with evidence of fibrosis

You may not qualify if:

• ALT or AST \>=5 × upper limit of normal (ULN)
• Total bilirubin (BILI) \>=1.3 milligram per deciliter (mg/dL). Individuals with documented Gilbert's syndrome may be enrolled if they experienced an isolated increase in total BILI of \>=1.3 mg/dL and direct BILI is \<=20% of total BILI; 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)
• HbA1c \>=9.0%
• Model for End-Stage Liver Disease (MELD) 3.0 score \>=12 unless the score is elevated in the absence of liver dysfunction (eg, Gilbert's syndrome)
• Phosphatidylethanol (PEth) \>=80 nanogram per milliliter (ng/mL) at Screening
• Known co-infection with any of the following: a. Human immunodeficiency virus; b. Hepatitis B virus; c. Hepatitis C virus (HCV); d. Hepatitis D virus; or e. Hepatitis E virus.
• Chronic liver disease from any other cause including, but not limited to, alcoholic liver disease; evidence of portal hypertension; viral hepatitis, or any history or evidence of cirrhosis; or decompensated liver disease such as clinical ascites, bleeding gastroesophageal varices, hepatorenal syndrome, or hepatic encephalopathy prior to Screening or Day 1.
• Current or history of excessive alcohol intake for \>=3 months within the 12-month period prior to Screening

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (43)

GSK Investigational Site

Arcadia, California, 91006, United States

RECRUITING

GSK Investigational Site

Covina, California, 91723, United States

RECRUITING

GSK Investigational Site

Los Angeles, California, 90057, United States

RECRUITING

GSK Investigational Site

Santa Maria, California, 93458, United States

RECRUITING

GSK Investigational Site

Cape Coral, Florida, 33914, United States

RECRUITING

GSK Investigational Site

Doral, Florida, 33016, United States

RECRUITING

GSK Investigational Site

Hialeah, Florida, 33016, United States

RECRUITING

GSK Investigational Site

Inverness, Florida, 34452, United States

RECRUITING

GSK Investigational Site

Jacksonville, Florida, 32216, United States

RECRUITING

GSK Investigational Site

Kissimmee, Florida, 34744, United States

RECRUITING

GSK Investigational Site

Lakeland, Florida, 33803, United States

RECRUITING

GSK Investigational Site

Maitland, Florida, 32751, United States

RECRUITING

GSK Investigational Site

Miami, Florida, 33135, United States

RECRUITING

GSK Investigational Site

Miami, Florida, 33155, United States

RECRUITING

GSK Investigational Site

Miami, Florida, 33156, United States

RECRUITING

GSK Investigational Site

Miami, Florida, 33184, United States

RECRUITING

GSK Investigational Site

Miami Lakes, Florida, 33014, United States

RECRUITING

GSK Investigational Site

Ocala, Florida, 34471, United States

RECRUITING

GSK Investigational Site

Palmetto Bay, Florida, 33157, United States

RECRUITING

GSK Investigational Site

Topeka, Kansas, 66606, United States

RECRUITING

GSK Investigational Site

Springfield, Missouri, 62703, United States

RECRUITING

GSK Investigational Site

St Louis, Missouri, 63141, United States

RECRUITING

GSK Investigational Site

Jersey City, New Jersey, 07059, United States

RECRUITING

GSK Investigational Site

East Syracuse, New York, 13057, United States

RECRUITING

GSK Investigational Site

New York, New York, 10036, United States

RECRUITING

GSK Investigational Site

Morehead City, North Carolina, 28557, United States

RECRUITING

GSK Investigational Site

Akron, Ohio, 44320, United States

RECRUITING

GSK Investigational Site

Springboro, Ohio, 45066, United States

RECRUITING

GSK Investigational Site

Austin, Texas, 78745, United States

RECRUITING

GSK Investigational Site

Austin, Texas, 78759, United States

RECRUITING

GSK Investigational Site

Brownsville, Texas, 78526, United States

RECRUITING

GSK Investigational Site

Dallas, Texas, 75243, United States

RECRUITING

GSK Investigational Site

DeSoto, Texas, 75115, United States

RECRUITING

GSK Investigational Site

Richmond, Texas, 77406, United States

RECRUITING

GSK Investigational Site

San Antonio, Texas, 78215, United States

RECRUITING

GSK Investigational Site

San Antonio, Texas, 78229, United States

RECRUITING

GSK Investigational Site

Seabrook, Texas, 77586, United States

RECRUITING

GSK Investigational Site

Tomball, Texas, 77375, United States

RECRUITING

GSK Investigational Site

Waco, Texas, 76710, United States

RECRUITING

GSK Investigational Site

Waco, Texas, 76712, United States

RECRUITING

GSK Investigational Site

West Jordan, Utah, 84088, United States

RECRUITING

GSK Investigational Site

Manassas, Virginia, 20110, United States

RECRUITING

GSK Investigational Site

Seattle, Washington, 98105, United States

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: December 12, 2025
• Primary Completion (Estimated): March 24, 2028
• Study Completion (Estimated): March 24, 2028
• Last Updated: April 16, 2026

Record last verified: 2026-03

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

US (43)