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    Summary
    EudraCT Number:2022-002538-14
    Sponsor's Protocol Code Number:218672
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2022-11-02
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedFrance - ANSM
    A.2EudraCT number2022-002538-14
    A.3Full title of the trial
    17-beta-Hydroxysteroid Dehydrogenase type 13 Minimization for the treatment of NASH (HORIZON): "A Double-Blind, Placebo-Controlled Phase 2b Study to Evaluate the Efficacy and Safety of GSK4532990 in Adults with Pre-Cirrhotic Non-Alcoholic Steatohepatitis".
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase 2b Study of GSK4532990 in Adults with Nonalcoholic Steatohepatitis (NASH)
    A.3.2Name or abbreviated title of the trial where available
    Phase 2b Study of GSK4532990 in Adults with NASH (HORIZON)
    A.4.1Sponsor's protocol code number218672
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorGlaxoSmithKline Research & Development Limited
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportGlaxoSmithKline Research & Development Limited
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGlaxoSmithKline Research & Development Limited
    B.5.2Functional name of contact pointClinical Trial Help Desk
    B.5.3 Address:
    B.5.3.1Street Address980 Great West Road
    B.5.3.2Town/ cityBrentford, Middlesex
    B.5.3.3Post codeTW8 9GS
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+442089909733
    B.5.6E-mailGSKClinicalSupportHD@gsk.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameGSK4532990 Injection, 200 mg/mL
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNN/A
    D.3.9.1CAS number 2409783-35-1
    D.3.9.2Current sponsor codeGSK4532990A
    D.3.9.3Other descriptive nameADS-006 sodium
    D.3.9.4EV Substance CodeSUB258556
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Nonalcoholic steatohepatitis (NASH)
    E.1.1.1Medical condition in easily understood language
    Nonalcoholic steatohepatitis (NASH) is a condition in which fat builds up in your liver. NASH causes inflammation, damage and scarring of the liver.
    E.1.1.2Therapeutic area Diseases [C] - Digestive System Diseases [C06]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 24.1
    E.1.2Level PT
    E.1.2Classification code 10053219
    E.1.2Term Non-alcoholic steatohepatitis
    E.1.2System Organ Class 10019805 - Hepatobiliary disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate whether GSK4532990 can cause one (or both) of fibrosis regression and/or NASH resolution in participants with NASH and bridging (F3) fibrosis.
    E.2.2Secondary objectives of the trial
    To evaluate GSK4532990 treatment effects on blood-based and imaging markers of liver fat, liver injury, and liver fibrosis in participants with NASH and bridging (F3) fibrosis.

    To assess the safety and tolerability of GSK4532990 in participants with NASH and bridging (F3) fibrosis.

    To evaluate the pharmacokinetics of GSK4532990.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Participant must be 18 to 75 years of age inclusive, at the time of screening. (Participants in South Korea must be ≥19 years of age.)
    2. Body Mass Index (BMI) ≥25 kg/m2 (all ethnic origins) except for Asian participants who qualify for the study with BMI ≥23 kg/m2 at Screening.
    3. A 12-lead ECG at Screening that, in the opinion of the Investigator, has no abnormalities that compromise participant’s safety in this study.
    4. In the opinion of the investigator, there are features of metabolic syndrome and NAFLD is the most likely cause of liver disease.
    5. 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. Either of the following are acceptable:
    a. A historical biopsy within 6 months of Screening 1 will be accepted as the baseline biopsy if confirmed by central scoring and if participant has not lost ≥5% body weight since the biopsy was performed. Note: See SoA footnote A and section 8.1.1 for further detail.
    b. If a qualifying historical liver biopsy has not been performed, the following criteria must be met prior to proceeding to biopsy. The study participant may undergo a liver biopsy once all the criteria in one of the options have been satisfied provided in protocol.
    6. Capable of giving signed informed consent prior to the performance of any study-specific procedures, as described in Section 10.1, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
    7. Able and willing to comply with all study assessments, including a liver biopsy at Week 52 and testing for HSD17B13 and PNPLA3 genotype, and adhere to the protocol schedule of activities.
    E.4Principal exclusion criteria
    1. Women of child-bearing potential (defined in Section 10.4.1).
    2. Cirrhosis (based on screening biopsy or historical biopsy showing definitive cirrhosis).
    3. United Network for Organ Sharing (UNOS) post-2016 Model for End-Stage Liver Disease (MELD) score ≥12. (Based on central laboratory measurement; 1 repeat test is allowed).
    4. Prior history of decompensated liver disease, including ascites, hepatic encephalopathy, or variceal bleeding.
    5. Platelets <140,000/μL, INR ≥1.3 (unless due to anticoagulant), or albumin <3.5g/dL. (Based on central laboratory measurement; 1 repeat test is allowed).
    6. ALT or AST ≥ 5x ULN or ≥ 250 U/L (Based on central laboratory measurement; 1 repeat test is allowed).
    7. ALP ≥ 2x ULN or ≥ 250 U/L (Based on central laboratory measurement; 1 repeat test is allowed).
    8. Fib4 ≥2.67 (Based on central laboratory measurement; 1 repeat test is allowed) AND FibroScan® LSM ≥ 20kPa
    9. Any history of kidney disease or kidney impairment defined by current hemodialysis/hemofiltration or an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 (using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation). (Based on central laboratory measurements; 1 repeat test is allowed)
    10. Urinary albumin creatinine ratio > 500 mg/g
    11. Known weight loss of ≥5% within 3 months prior to Screening.
    12. Chronic hepatitis B virus (HBV) infection, confirmed by positive hepatitis B surface antigen [HBsAg] serology. (Based on central laboratory measurements).
    13. Chronic hepatitis C virus (HCV) infection, confirmed by positive HCV antibody serology and detectable HCV RNA. Participants who are anti-HCV positive, but HCV RNA negative are eligible providing treatment for HCV infection occurred 2 years or more prior to screening (Based on central laboratory measurements).
    14. Other causes of liver disease including, but not limited to, alcohol-related liver disease, autoimmune disorders (e.g., primary biliary cholangitis, primary sclerosing cholangitis, and autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, hemochromatosis, and alpha-1-antitryspin deficiency, based on medical history, blood tests including autoantibody serology and serum immunoglobulins and/or the liver histology reported by the central lab.
    15. 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).
    16. History of liver transplantation.
    17. Current, or history of hepatocellular carcinoma (HCC).
    18. HIV infection or seropositivity for anti-HIV antibody (central laboratory measurements).

    For further information please refer to the study Protocol Amendment 1.
    E.5 End points
    E.5.1Primary end point(s)
    • Achieving ≥ 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.
    • 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.

    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 52
    E.5.2Secondary end point(s)
    • Change from baseline in Pro-C3 at 24 weeks and 52 weeks.
    • Change from baseline in liver fat using MRI-PDFF at 24 weeks and 52 weeks.
    • Change from baseline in liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE™) at 24 weeks and 52 weeks.
    • Change from baseline in Enhanced Liver Fibrosis (ELF™) Score and its individual components (HA, PIIINP, TIMP-1) at 24 weeks and 52 weeks.
    • Achieving ≥30% reduction from baseline in MRI-PDFF at 24 weeks.
    • Achieving ≥30% reduction from baseline in MRI-PDFF at 52 weeks.
    • Change from baseline in ALT, AST and GGT at 24 weeks and 52 weeks.

    Clinical assessments including, but not limited to:
    • Occurrence of AEs and SAEs,
    • Change from baseline in vital signs at each Visit,
    • Change from baseline in key laboratory measurements at each Visit.

    • In a subset of participants with intensive PK sampling: plasma pharmacokinetic (PK) parameters of GSK4532990 including area under the concentration-time curve from time zero (pre-dose) to the last quantifiable concentration (AUC0-t), maximum observed concentration (Cmax), time of occurrence of Cmax (tmax), apparent terminal phase half-life (t1/2), apparent clearance (CL/F), and apparent terminal phase volume of distribution (Vz/F).
    • Occurrence of anti-drug antibodies (ADA) to GSK4532990.
    E.5.2.1Timepoint(s) of evaluation of this end point
    52 weeks
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA26
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Canada
    India
    Japan
    Korea, Republic of
    Mexico
    United States
    France
    Spain
    Greece
    Italy
    Belgium
    Turkey
    United Kingdom
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months1
    E.8.9.1In the Member State concerned days26
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months4
    E.8.9.2In all countries concerned by the trial days4
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 204
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 42
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 52
    F.4.2.2In the whole clinical trial 246
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    After the trial, on-going management of disease will be provided by the subjects’ healthcare providers or their pre-trial status.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2022-12-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2023-01-16
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
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