A Study Evaluating the Efficacy and Safety of Pegozafermin in Participants With MASH and Fibrosis (ENLIGHTEN-fibrosis)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

89bio Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

7 Nov 2024 → ongoing

Decision date (initial)

2025-09-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

89bio, Inc

External identifiers

EU CT number

2023-509912-27-00

WHO UTN

U1111-1300-7180

ClinicalTrials.gov

NCT06318169

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Pharmacodynamic, Safety, Therapy

At interim analysis: To evaluate the effect of pegozafermin compared to placebo on liver histology at 52 weeks relative to baseline biopsy.
At study completion: To evaluate the effect of pegozafermin compared to placebo in reducing the risk of clinical outcome composite endpoint.

Secondary objectives 11

1. 1_At interim analysis: To evaluate the effect of pegozafermin compared to placebo on liver-related noninvasive tests (NITs) at 52 weeks
2. 2_At interim analysis: To evaluate the effect of pegozafermin compared to placebo on additional liver histology endpoints at 52 weeks relative to baseline biopsy
3. 3_At interim analysis: To evaluate the effect of pegozafermin compared to placebo on additional NITs at 52 weeks
4. 4_At interim analysis: To evaluate the metabolic effects of pegozafermin compared to placebo at 52 weeks
5. 5_At interim analysis: To evaluate the safety and tolerability of pegozafermin compared to placebo after 52 weeks of treatment
6. 6_At study completion: To demonstrate the effect of pegozafermin compared to placebo in reducing the risk of progression to cirrhosis
7. 7_At study completion: To demonstrate the effect of pegozafermin compared to placebo on liver-related NITs
8. 8_At study completion: To evaluate the effect of pegozafermin compared to placebo on additional liver histology endpoints
9. 9_At study completion: To evaluate the effect of pegozafermin compared to placebo on additional liver-related NITs
10. 10_At study completion: To evaluate the metabolic effects of pegozafermin compared to placebo
11. 11_At study completion: To evaluate the safety and tolerability of pegozafermin compared to placebo

Conditions and MedDRA coding

Metabolic Dysfunction-Associated Steatotic Liver Disease(MASH) / Nonalcoholic Steatohepatitis (NASH) With Fibrosis

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

EMA paediatric investigation plan (PIP)

EMEA-003619-PIP01-24

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. 1_Males or non-pregnant females aged between 18 and 80 years (inclusive) at time of signing the informed consent form (ICF)
2. 2_Biopsy-confirmed MASH, either within 6 months of screening visit [with additional requirements] or obtained during screening period in: a_ Group A: Subjects with fibrosis stage F2 or F3 per NASH CRN System and NAS >=4, with a score of at least 1 in each of steatosis, ballooning degeneration, and lobular inflammation b_ Group B: Subjects who do not meet NAS criteria for Group A and have F3 fibrosis and a score of at least 1 in steatosis and at least 1 in lobular inflammation. This will include subjects with NAS <4 and/or a ballooning degradation score of 0.
3. 3_Body mass index (BMI) at Screening ≥25.0 kg/m2 (≥23 kg/m2 for Asian countries)

Exclusion criteria 4

1. 1_Chronic liver diseases other than MASH/NASH
2. 2_Evidence of cirrhosis
3. 3_Have type 1 diabetes or poorly controlled type 2 diabetes
4. 4_Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >=250 U/L

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1_Proportion of participants achieving the co-primary endpoints measured at 52 weeks of: _ Improvement in fibrosis by ≥1 stage without worsening of steatohepatitis -resolution of steatohepatitis without worsening of fibrosis

Secondary endpoints 4

1. 1_Change From Baseline in Liver Fat as Assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) at Week 52
2. 2_Percent Change from Baseline in Alanine Aminotransferase (ALT) at Week 52 and Month 36
3. 3_Time to First Occurrence of Disease Progression as Measured by Composite of Protocol -Specified Clinical Events Up to Month 36
4. 4_Absolute change from baseline in ELF score at 52 weeks

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

89bio Inc.

Sponsor organisation

89bio Inc.

Address

655 Montgomery Street Floor 15th

City

San Francisco

Postcode

94111-2635

Country

United States

Scientific contact point

Organisation

89bio Inc.

Contact name

enlightenscientific

Public contact point

Organisation

89bio Inc.

Contact name

enlighten

Third parties 8

Locations

10 EU/EEA countries · 82 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

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

Documents 135 files

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

Application history

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