A pivotal clinical study to investigate the safety and efficacy of efimosfermin alfa injection in participants with biopsyconfirmed F2- or F3-stage MASH (BOS-580-301)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Decision date (initial)

2026-06-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2025-523675-39-00

ClinicalTrials.gov

NCT07221227

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Pharmacokinetic, Efficacy

Week 52 Analysis:
To determine the effect of efimosfermin compared to placebo on histologic resolution of MASH and improvement in fibrosis after 52 weeks treatment.

Month 48 Analysis
To determine the time to a composite clinical outcome following treatment with efimosfermin compared to placebo after up to 48 months treatment.

Secondary objectives 11

1. To assess the effects of efimosfermin on safety and tolerability.
2. To determine the effect of efimosfermin compared to placebo on histologic resolution of MASH and improvement in fibrosis after 52 weeks and 48 months of treatment.
3. To assess the effects of efimosfermin on VCTE-LSM and CAP scores.
4. To assess the effects of efimosfermin on MRE score.
5. To assess the effects of efimosfermin on ELF score.
6. To assess the effects of efimosfermin on HFF and ALT normalization.
7. To assess the effects of efimosfermin on glycemic and metabolic biomarkers.
8. To assess the effects of efimosfermin on lipids.
9. To assess the immunogenicity of efimosfermin.
10. To assess the effects of efimosfermin on patient-reported outcomes.
11. To assess the steady-state PK of efimosfermin.

Conditions and MedDRA coding

Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

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

Exclusion criteria 15

1. Contraindication or ineligibility for percutaneous liver biopsy.
2. ALT or AST >=5*upper limit of normal (ULN).
3. 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.
4. Serum albumin <=3.5 grams per deciliter (g/dL).
5. 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.
6. Alkaline phosphatase (ALP) >=2*ULN.
7. 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.
8. 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.
9. Alpha-fetoprotein >=20 nanogram per milliliter (ng/mL).
10. Glycated hemoglobin >=9.0%.
11. Model for End-Stage Liver Disease score >=12 unless the score is elevated in the absence of liver dysfunction (e.g., Gilbert's syndrome).
12. Phosphatidyl ethanol (PEth) >=80 ng/mL at Screening.
13. Evidence of infection with any of the following: - Human immunodeficiency virus - Hepatitis B virus (detectable HBsAg at Screening) - Hepatitis C virus (HCV)
14. 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 on screening liver biopsy; or decompensated liver disease such as clinical ascites, bleeding gastroesophageal varices, hepatorenal syndrome, or hepatic encephalopathy prior to Screening or Day 1.
15. Current or history of excessive alcohol intake for >=3 months within the 12-month period prior to Screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Proportion of participants experiencing improvement in fibrosis by >=1 stage and no worsening of steatohepatitis at Week 52.
2. Proportion of participants experiencing resolution of steatohepatitis reading and no worsening of MASH CRN fibrosis score at Week 52.
3. Time from randomization to an adjudicated composite liver-related clinical outcome.

Secondary endpoints 11

1. For all participants at Week 52 and at Month 48 Number of participants with treatment-emergent adverse events (TEAEs) and TEAEs by severity Number of participants with TEAEs leading to discontinuation and TEAEs leading to discontinuation by severity Number of participants with Grade 3 and Grade 4 laboratory abnormalities.
2. Proportion of participants with: resolution of steatohepatitis on histopathological reading and improvement in liver fibrosis >=1 stage at Week 52 improvement in fibrosis >=1 stage and no worsening of Steatohepatitis at Month 48 improvement in fibrosis >=2 stage and no worsening of Steatohepatitis at Week 52 and Month 48 resolution of steatohepatitis and no worsening of MASH CRN score at Month 48
3. Absolute and relative change from baseline to Week 52 and Month 48 in VCTE-LSM and CAP scores for all participants. Achieving a change from baseline in VCTE-LSM ≥ 30% at Week 52 and Month 48.
4. Absolute and relative change from baseline to Week 52 and Month 48 in the subset of participants with MRE scores.
5. Absolute and relative change from baseline to Week 52 and Month 48 in ELF score for all participants. Achieving improvement in ELF score of ≥ 0.5.
6. Absolute and relative change from baseline to Week 52 and Month 48 in HFF by MRI-PDFF for all participants. Absolute and relative change from baseline to Week 52 and Month 48 in ALT, AST, and ALT/AST ratio for all participants. Achieving ALT and HFF normalization at Week 52 and Month 48. Achieving HFF ≤ 5%.
7. Change from baseline to Week 52 and Month 48 in HbA1c for participants with T2DM. Change from baseline to Week 52 and Month 48 in body weight for all participants.
8. Change from baseline in fasting total cholesterol, LDL-C, HDL-C, and fasting triglycerides at Week 52 and Month 48 for all participants.
9. Proportion of participants with antidrug and antiFGF21 antibody (ADA).
10. Change from baseline in CLDQ-NASH domain and total scores at Week 52 and Month 48. Change from baseline in SF-36 component and domain scores at Week 52 and Month 48.
11. Serum drug Concentration of efimosfermin alfa.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

79 New Oxford Street

City

London

Postcode

WC1A 1DG

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 16

Locations

9 EU/EEA countries · 82 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 202 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications