Last updated: 07/09/2026 14:10:34

A pivotal clinical study to investigate the safety and efficacy of efimosfermin compared with placebo in adult participants with compensated cirrhosis due to Metabolic dysfunction-associated steatohepatitis (MASH)NEBULA-1

GSK study ID
306300
Clinicaltrials.gov ID
Not applicable
EudraCT ID
Not applicable
EU CT Number
2026-525755-82
Trial status
Not yet recruiting
Not yet recruiting
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A Phase 3, double-blind, randomized, placebo controlled, 2-arm study to investigate the safety and efficacy of efimosfermin alfa injection in adult participants with compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis (NEBULA-1)
Trial description: This study will investigate the safety and efficacy of efimosfermin alfa in participants with compensated cirrhosis due to MASH.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:

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

Timeframe: From Randomization (Day 1) to Week 356 (end of treatment)

Secondary outcomes:

Proportion of participants achieving change from Baseline in vibration-controlled transient elastography- liver stiffness measurement (VCTE-LSM) and in enhanced liver fibrosis (ELF) score

Timeframe: Baseline (Day 1), Week 96, and Week 260

Proportion of participants achieving change from Baseline in VCTE-LSM

Timeframe: Baseline (Day 1), Week 96, and Week 260

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

Timeframe: Week 96, Week 260 and Week 356 (end of treatment)

Proportion of participants with TEAEs leading to discontinuation and TEAEs leading to discontinuation by severity

Timeframe: Week 96, Week 260 and Week 356 (end of treatment)

Proportion of participants with Grade 3 and Grade 4 laboratory abnormalities

Timeframe: Week 96, Week 260 and Week 356 (end of treatment)

Absolute change from Baseline in VCTE-LSM

Timeframe: Baseline (Day 1), Week 96, Week 260, and Week 356 (end of treatment)

Relative change from Baseline in VCTE-LSM

Timeframe: Baseline (Day 1), Week 96, Week 260, and Week 356 (end of treatment)

Absolute change from Baseline in Magnetic resonance elastography (MRE) scores

Timeframe: Baseline (Day 1), Week 96, and Week 260

Relative change from Baseline in MRE scores

Timeframe: Baseline (Day 1), Week 96, and Week 260

Absolute change from Baseline in ELF scores

Timeframe: Baseline (Day 1), Week 96, Week 260, and Week 356 (end of treatment)

Relative change from Baseline in ELF scores

Timeframe: Baseline (Day 1), Week 96, Week 260, and Week 356 (end of treatment)

Proportion of participants experiencing improvement in ELF score

Timeframe: Week 96, Week 260 and Week 356 (end of treatment)

Change from Baseline in glycated hemoglobin (HbA1c) (Percentage of HbA1c) in participants with Type 2 Diabetes Mellitus (T2DM)

Timeframe: Baseline (Day 1), Week 96, Week 260 and Week 356 (end of treatment)

Change from Baseline in fasting glucose (Millimole per Liter) in participants with T2DM

Timeframe: Baseline (Day 1), Week 96, Week 260 and Week 356 (end of treatment)

Change from Baseline in fasting total cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)- cholesterol, and fasting triglycerides (Millimoles per liter)

Timeframe: Baseline (Day 1), Week 96, Week 260 and Week 356 (end of treatment)

Change from Baseline in Patient-reported outcomes measurement information system (PROMIS)-Fatigue score

Timeframe: Baseline (Day 1), Week 96, Week 260 and Week 356 (end of treatment)

Change from Baseline in Chronic Liver Disease Questionnaire-Nonalcoholic Steatohepatitis (CLDQ-NASH) domain and total score

Timeframe: Baseline (Day 1), Week 96, Week 260 and Week 356 (end of treatment)

Change from Baseline in Short Form-36 (SF-36) component and domain scores

Timeframe: Baseline (Day 1), Week 96, Week 260 and Week 356 (end of treatment)

Interventions:
Drug: Efimosfermin alfa
Drug: Placebo
Enrollment:
1740
Observational study model:
Not applicable
Primary completion date:
2033-25-07
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Metabolic Dysfunction-Associated Steatohepatitis
Product
Not applicable
Collaborators
Not applicable
Study date(s)
July 2026 to August 2033
Type
Interventional
Phase
3

Participation criteria

Sex
Female & Male
Age
18 - 75 Years
Accepts healthy volunteers
No
  • Participants aged between 18 and 75 years at enrollment.
  • Participants with compensated cirrhosis due to MASH, confirmed by non-invasive assessments.
  • Participants with other chronic liver diseases.
  • Participants with evidence or history of decompensated liver disease or hepatocellular carcinoma.
Inclusion and exclusion criteria
Inclusion criteria:

    Participants aged between 18 and 75 years at enrollment.

    • Participants with compensated cirrhosis due to MASH, confirmed by non-invasive assessments.
    • Participants with history or presence of at least two components of metabolic syndrome.
Exclusion criteria:

    Participants with other chronic liver diseases.

    • Participants with evidence or history of decompensated liver disease or hepatocellular carcinoma.
    • Participants with history of Type 1 diabetes mellitus or major Type 2 diabetes complications.
    • Participants with history or evidence of chronic pancreatic disease; pancreatic injury or acute pancreatitis within 6 months before screening.
    • Participants with a recent history or planned surgical procedures or medications intended to produce significant weight loss.
    • Participants with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >=5 times upper limit normal (ULN).
    • Participants with current or history of excessive alcohol intake.

Trial location(s)

No location data available.

Study documents

No study documents available.

Results overview

Study Results yet to be posted

Recruitment status
Not yet recruiting
Actual primary completion date
Not applicable
Actual study completion date
Not applicable

Plain language summaries

Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

Additional information about the trial

Additional information
Not applicable
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