Study to Evaluate the Efficacy and Safety of Pegozafermin in Participants With Compensated Cirrhosis Due to MASH (ENLIGHTEN-Cirrhosis)

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

30 Oct 2024 → ongoing

Decision date (initial)

2024-10-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

89bio, Inc

External identifiers

EU CT number

2023-510395-31-00

WHO UTN

U1111-1300-7189

ClinicalTrials.gov

NCT06419374

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Pharmacokinetic, Efficacy

At interim analysis: To evaluate the effect of pegozafermin compared to placebo on regression of fibrosis at 24 months relative to baseline biopsy.
At study completion: To evaluate the effect of pegozafermin compared to placebo in reducing the risk of clinical outcomes measured as a composite endpoint

Secondary objectives 4

1. 1_At interim analysis: To evaluate the effect of pegozafermin compared to placebo on liver-related noninvasive tests
2. 2_At interim analysis: To evaluate the safety and tolerability of pegozafermin compared to placebo
3. 3_At study completion: To evaluate the effect of pegozafermin compared to placebo on liver-related clinical endpoints and noninvasive tests
4. 4_At study completion:To evaluate the the safety and tolerability of pegozafermin compared to placebo

Conditions and MedDRA coding

Metabolic Dysfunction-Associated Steatohepatitis (MASH) with Compensated Cirrhosis

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 1_Males or non-pregnant females aged between 18 and 75 years (inclusive) at time of signing the informed consent form (ICF)
2. 2_Presence of type 2 diabetes mellitus (T2DM) diagnosed at least 3 months before Screening or at least two metabolic risk factors as defined in the protocol
3. 3_Biopsy-confirmed fibrosis stage F4 MASH (per non-alcoholic steatohepatitis [NASH] Clinical Research Network (CRN) system) with compensated cirrhosis
4. 4_Body mass index (BMI) at Screening ≥25.0 (≥23.0 for Asian subjects) and <50.0 kg/m2

Exclusion criteria 6

1. 1_Liver disorder other than MASH
2. 2_History or evidence of hepatic decompensation
3. 3_History or evidence of hepatocellular carcinoma
4. 4_Have type 1 diabetes mellitus or unstable type 2 diabetes mellitus
5. 5_ALT or aspartate aminotransferase (AST) ≥250 units per liter (U/L)
6. 6_Participants taking vitamin E (>400 international units [IU]/day) must be on stable dose for at least 6 months prior to screening and up to randomization

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1_At interim analysis: Proportion of subjects achieving fibrosis regression, defined as improvement in fibrosis by ≥1 stage, at Month 24 biopsy relative to baseline biopsy
2. 2_At study completion: Time to First Occurrence of Disease Progression as Measured by Composite of Protocol -Specified Clinical Events

Secondary endpoints 7

1. 1_At interim analysis and study completion: Change from baseline in ELF score
2. 2_At interim analysis and study completion: Change from baseline in ALT
3. 3_At interim analysis and study completion: Change from baseline in FibroScan VCTE
4. 4_At study completion: Proportion of subjects who develop CSPH
5. 5_At study completion: Time to progression to large gastric or esophageal varices and/or varices with “red-wale” signs or endoscopic treatment of esophageal or gastric varices
6. 6_At study completion: Time to clinically important ascites as determined by the onset of Grade ≥2 (clinically apparent) ascites leading to diagnostic paracentesis or initiation of specific treatment for ascites (e.g., diuretics, therapeutic paracentesis, or TIPS)
7. 7_At study completion: Time to overt hepatic encephalopathy (altered mental status without alternate explanation requiring acute medical attention and either initiation of specific therapy or modification of existing treatment)

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

9 EU/EEA countries · 69 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 82 files

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

Application history

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