Phase 2b Study of GSK4532990 in Adults with NASH (HORIZON)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

30 Mar 2023 → 19 May 2026

Decision date (initial)

2024-03-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-507503-62-00

EudraCT number

2022-002538-14

ClinicalTrials.gov

NCT05583344

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate whether GSK4532990 can cause one (or both) of fibrosis regression and/or NASH resolution in participants with NASH and bridging (F3) fibrosis

Secondary objectives 4

1. To evaluate whether GSK4532990 can cause one (or both) of fibrosis regression and/or NASH resolution in participants with NASH and F3 and in participants with NASH and F4 fibrosis (pooled cohort)
2. To evaluate GSK4532990 treatment effects on blood-based and imaging markers of liver fat, liver injury, and liver fibrosis in participants with NASH and F3 fibrosis and in pooled cohort of participants with NASH and F3 and NASH and F4 fibrosis.
3. To assess the safety and tolerability of GSK4532990 in participants with NASH and F3 fibrosis; in participants with NASH and F4 fibrosis and in pooled cohort of participants with NASH and F3 and NASH and F4 fibrosis
4. To evaluate GSK4532990 exposure parameters in participants with NASH and F3 fibrosis and in participants with NASH and F4 fibrosis

Conditions and MedDRA coding

Non-alcoholic Fatty Liver Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Participant must be 18 to 75 years of age inclusive, at the time of screening.
2. Body Mass Index (BMI) ≥25 kilogram per meter square (kg/m^2) (all ethnic origins) except for Asian participants who qualify for the study with BMI ≥23 kg/m2 at Screening.
3. In the opinion of the investigator, there are features of metabolic syndrome and NAFLD is the most likely cause of liver disease. Metabolic syndrome may include type 2 diabetes mellitus (T2DM), obesity, dyslipidemia and hypertension.
4. "The liver biopsy must show a NAS ≥4 with at least 1 point each in steatosis, inflammation, and ballooning and Fibrosis 3 using NASH CRN Scoring System, confirmed by central scoring."
5. Capable of giving signed informed consent prior to the performance of any study-specific procedures
6. Able and willing to comply with all study assessments.
7. "A female participant is eligible to participate, if she is not pregnant or breastfeeding and one of the following conditions applies: • Is a woman of nonchildbearing potential (WONCBP) as defined in Section 10.4 Contraception and Barrier Guidance OR • Is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of <1%, as described in Section 10.4. Contraceptive measures must start from the time of negative serum pregnancy test at screening and at least 28 days before first administration of study intervention. Contraceptive measures should then continue during the study intervention period, and for at least 18 weeks after the last administration of study intervention. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated in relationship to the first dose of study intervention). o A WOCBP must have a negative highly sensitive pregnancy test (serum or urine as required by local regulations) within 24 hours before the first dose of study intervention, see Section 8.2.5 Pregnancy Testing. "

Exclusion criteria 3

1. Current alcohol consumption ≥14 standard drinks (24 units, 196 g ethanol) per week for females or ≥21 standard drinks (37 units, 294g ethanol) per week for males. One standard drink is equivalent to: 12 US fluid ounces (oz) beer (5% alcohol); 5 oz of wine (12% alcohol), or 1.5 oz of 80 proof spirits (40% alcohol).
2. Weight reduction surgery (including gastric banding and intragastric balloon insertion) within 2 years of Screening 1.
3. History of cancer within previous 2 years from Screening 1, except adequately

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. "Achieving greater or equal to 1 stage improvement in histological fibrosis (Clinical Research Network [CRN] scoring) with no worsening of NASH (defined as no increase in the NAFLD Activity Score [NAS] for steatosis, ballooning, or inflammation) at 52 weeks. "
2. "Achieving NASH resolution with no worsening of fibrosis (defined as no increase in CRN fibrosis score) at 52 weeks. Resolution of NASH is defined as a ballooning score of 0 and an inflammation score of 0-1. "

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

G S K House, 980 Great West Road 980 Great West Road

City

Brentford

Postcode

TW8 9GS

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 19

Locations

5 EU/EEA countries · 29 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 81 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