A study to investigate the safety and efficacy of GSK4532990 compared with placebo in adult participants aged 18 to 65 years with alcohol-related liver disease.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

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

26 Dec 2024 → ongoing

Decision date (initial)

2024-10-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Dose response

Safety Lead-in
To assess safety and tolerability of a single subcutaneous dose of GSK4532990.
Main Study Period
To evaluate the efficacy of GSK4532990 on the reduction from baseline in LSM / MELD in participants with ALD.

Secondary objectives 3

1. Safety Lead-in To assess the effect of hepatic impairment on the plasma PK parameters of GSK4532990.
2. Main Study Period To evaluate the efficacy of GSK4532990 in participants with ALD.
3. Main Study Period To evaluate GSK4532990 exposure parameters in participants with ALD

Conditions and MedDRA coding

Liver Diseases, Alcoholic

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

o IPD Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: Sharing Clinical Trial Data’ on the GSK Study Register (www.gsk-studyregister.com). o IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months. o IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Safety Lead-in Participant must be 18 to 70 years of age inclusive, at the time of screening. (Participants in South Korea must be ≥19 years of age.). INC#1
2. Safety Lead-in Capable of giving signed informed consent prior to the performance of any study-specific procedures, as described in Section 10.1.3, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. INC#2
3. Safety Lead-in Participant has liver cirrhosis with a grade of hepatic impairment that can be classified as a discrete CTP class. INC#3 Participants must: − Have a clinical diagnosis of liver cirrhosis in the participant’s medical history corroborated by previous liver biopsy, medical imaging or compatible biochemical profile and -Be consistently classified during screening as one of the following CTP classes: − CTP A: Score 5-6; or CTP B: Score 7-9 − Additional exploratory group CTP C: Score >9
4. Safety Lead-in Able and willing to comply with all study assessments and adhere to the protocol schedule of activities. INC#4
5. Safety Lead-in In the opinion of the investigator, there is a history of alcohol consumption compatible with either ALD or MetALD. Participants may have concomitant features of the metabolic syndrome such as type 2 diabetes mellitus (T2DM), obesity, dyslipidemia and hypertension. Alcohol consumption typical of a diagnosis of MetALD or ALD may include for men: consuming 5 or more standard drinks on any day or 15 or more standard drinks per week or ≥26 units per week or ≥210g ethanol per week (average 30g per day or ≥70g on any day per week); for women: consuming 4 or more standard drinks on any day or 8 or more standard drinks per week or ≥14 units per week or ≥112g ethanol per week (average 16g per day or ≥56g on any day per week). INC#5 NB: 1 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). One standard drink is equivalent to 1.7 UK units or 14g of ethanol.
6. Safety Lead-in A female participant is eligible to participate, if she is not pregnant or breastfeeding and one of the following conditions applies: INC#6 − Is a woman of nonchildbearing potential (WONCBP) as defined in Section 10.4 (Appendix 4: Contraceptive 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 at least 28 days prior to the first dose of study intervention and should continue during the study intervention period, for a minimum of 18 weeks after the last dose 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). 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 8.3.5 Pregnancy testing).
7. Main Study Period Participant must be 18 to 65 years of age inclusive, at the time of screening. (Participants in South Korea must be ≥19 years of age.) INC#1
8. Main Study Period Capable of giving signed informed consent prior to the performance of any study-specific procedures, as described in Section 10.1.3. INC#2
9. Main Study Period Willingness to comply with the requirements and restrictions listed in the informed consent form (ICF), in this protocol and listed assessments, including testing for HSD17B13, SERPINA1, MBOAT7, TM6SF2 and PNPLA3 genotypes, and adhere to the protocol schedule of activities. INC#3
10. Main Study Period In the opinion of the investigator, there is a history of alcohol consumption compatible with either ALD or MetALD. Participants may have concomitant features of the metabolic syndrome such as type 2 diabetes mellitus (T2DM), obesity, dyslipidemia and hypertension. Alcohol consumption typical of a diagnosis of MetALD or ALD may include for men: consuming 5 or more standard drinks on any day or 15 or more standard drinks per week or ≥26 units per week or ≥210g ethanol per week (average 30g per day or ≥70g on any day per week); for women: consuming 4 or more standard drinks on any day or 8 or more standard drinks per week or ≥14 units per week or ≥112g ethanol per week (average 16g per day or ≥56g on any day per week). INC#4
11. Main Study Period A female participant is eligible to participate, if she is not pregnant or breastfeeding and one of the following conditions applies: INC#5 − Is a woman of nonchildbearing potential (WONCBP) as defined in Section 10.4 (Appendix 4: Contraceptive 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 at least 28 days prior to the first dose of study intervention and should continue during the study intervention period, for a minimum of 18 weeks after the last dose 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. 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 8.3.5 Pregnancy testing).
12. Main Study Period Participants using any of the specified medications listed below can be included, but only if all these requirements are met: INC#6 − the dose has been stable for ≥3 months prior to D1, and − the participant is expected to continue the same dosing regimen throughout study participation. The specified medications are: incretin analogues such as glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), or glucagon receptor agonist, alone or in combination; PPAR agonists (e.g., pioglitazone, saroglitazar), sodium glucose cotransporter 2 (SGLT2) inhibitors; thyroid hormone receptor beta agonists; farnesoid X receptor (FXR) agonists; fatty acid synthase inhibitors; fibroblast growth factor 21 (FGF21) agonists; or Vitamin E (at doses greater than 400 IU/day). NOTE: If a switch to another medication within the same class is required, this will only be permitted if the new medication dose is equivalent to the prior medication dose. Switches to a different medication class are not permitted during the study.

Exclusion criteria 91

1. Safety Lead-in Self-reported alcohol abstinence ≥4 months prior to Screening 1. EXC#1
2. Safety Lead-in Any history of anaphylaxis or hypersensitivity to GSK4532990 or any of the constituents of the injection. EXC#25
3. Safety Lead-in Current use of other GalNAc conjugated siRNA therapy. EXC#26
4. Safety Lead-in Chronic or acute, including partial, known portal vein thrombosis. EXC#18
5. Safety Lead-in Previous use of other investigational therapies targeting HSD17B13 and/or PNPLA3. EXC#27
6. Safety Lead-in Prior investigational therapies unless beyond washout period of at least 5 half-lives or 6 weeks (whichever is longer) from D1. EXC#28
7. Safety Lead-in Recent major surgery within previous 6 weeks prior to D1. EXC#29
8. Safety Lead-in Current use of anticoagulants that increase prothrombin time (PT) and INR. EXC#8
9. Safety Lead-in Any symptomatic infection, including COVID-19. Participants may be eligible 2 weeks after resolution of symptoms. EXC#30
10. Safety Lead-in Current or planned participation in any clinical trial of investigational therapies or medical devices. Participation in clinical trial of investigational software application for the treatment of Alcohol Use Disorder is permitted. EXC#31
11. Safety Lead-in Clinical suspicion of rhabdomyolysis during the screening period. EXC#32
12. Safety Lead-in AST < ULN at either Screening 1 or Screening 2 (1 repeat test is allowed for each screening visit). EXC#4
13. Safety Lead-in Clinical suspicion of a bleeding episode during the screening period related to either portal hypertension or low blood fibrinogen level (LLN) in the opinion of investigator. EXC#33
14. Safety Lead-in Any abnormality on a 12-lead ECG during the screening period that, in the opinion of the Investigator, compromises the participant’s safety in this study. EXC#34
15. Safety Lead-in Average of triplicate QTc >450 msec for males or QTc >470 msec for females or QTc >480 msec in participants with bundle branch block (1 repeat test is allowed). EXC#35
16. Safety Lead-in Prior transjugular intrahepatic portosystemic shunt (TIPSS) insertion. EXC#19
17. Main Study Period Self-reported alcohol abstinence ≥4 months prior to Screening 1. EXC#1
18. Main Study Period Meeting any definition of organ system failure as defined by the North American Consortium for Study of End-stage Liver Disease (NACSELD) (see Section 10.10.5). EXC#2
19. Main Study Period Average MELD 3.0 score ≥ 22 from measurements taken at Screening 1 and 2. (Based on central laboratory measurement; 1 repeat test is allowed for each screening visit). EXC#3
20. Main Study Period Average LSM <15kPa from measurements taken at Screening 1 and Screening 2 (1 repeat test is allowed for each screening visit). EXC#4
21. Safety Lead-in Any history of chronic kidney disease or kidney impairment defined by current or previous hemodialysis/hemofiltration; or an estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2 at either Screening 1 or Screening 2 (using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation). (Based on central laboratory measurement; 1 repeat test is allowed for each screening visit). EXC#9
22. Main Study Period ELF < 9.8 at Screening 1 (Based on central laboratory measurement; 1 repeat test is allowed). EXC#5
23. Safety Lead-in ALP ≥250 U/L at either Screening 1 or Screening 2 (Based on central laboratory measurement; 1 repeat test is allowed for each screening visit). EXC#5
24. Safety Lead-in Positive hepatitis C RNA test result at Screening (Based on local or central laboratory measurements; 1 repeat test is allowed) or within 3 months prior to first dose of study intervention. Note: Test is optional and participants with negative hepatitis C antibody test are not required to also undergo hepatitis C RNA testing. EXC#13
25. Safety Lead-in Other primary causes of liver disease (including but not limited to 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. ALD or Met-ALD must be the primary cause of liver disease. EXC#14
26. Safety Lead-in Current, or history of known hepatocellular carcinoma (HCC). EXC#15
27. Safety Lead-in Current or ongoing malignancy (except for basal cell carcinoma or uterine carcinoma-in-situ) at Screening 1. Participants under evaluation for possible malignancy at Screening 1 are not eligible. EXC#16
28. Safety Lead-in Urinary albumin to creatinine ratio ≥300 mg/g creatinine (≥33.9 mg/mmol creatinine) at Screening 1 (Based on central laboratory measurement; 1 repeat test is allowed for each screening visit). EXC#10
29. Safety Lead-in All organ transplant recipients, except for history of corneal transplants, or current listing or active consideration for liver transplant during the Screening period. EXC#17
30. Main Study Period Psychosocial features that, in the opinion of the investigator, increase the likelihood of loss to follow-up including, but not limited to, any of the following: EXC#6 − Prior history of frequent non-attendance at pre-arranged healthcare appointments or discharge from hospital admission against medical advice − Recent (<1 year) substance use or substance use disorder, as evidenced by positive urine toxicology screen that is not explained by medical prescription or participant history. Occasional cannabis use is permitted. − Inadequate social support structures such as spouse, family, fixed housing or friends − Prior history of psychosis or mania or other chronic severe mental health disorder − History of intentional self-harm and/or suicide attempts within the preceding 5 years − Prior history of criminal convictions, excluding driving offences, within the preceding 5 years
31. Main Study Period AST < ULN at either Screening 1 or Screening 2 ((Based on central laboratory measurement; 1 repeat test is allowed for each screening visit). EXC#7
32. Main Study Period ALP ≥250 U/L at either Screening 1 or Screening 2 (Based on central laboratory measurement; 1 repeat test is allowed for each screening visit). EXC#8
33. Main Study Period ALT or AST ≥250 U/L at either Screening 1 or Screening 2 (Based on central laboratory measurement; 1 repeat test is allowed for each screening visit). EXC#9
34. Safety Lead-in Platelets <60,000/μL, INR >2.3, or albumin <2.8 g/dL at either Screening 1 or Screening 2 (Based on central laboratory measurement; 1 repeat test is allowed for each screening visit). EXC#7
35. Main Study Period Platelets <60,000/μL, INR >2.3, or albumin <2.8 g/dL at either Screening 1 or Screening 2 (Based on central laboratory measurement; 1 repeat test is allowed for each screening visit). EXC#10
36. Main Study Period Current use of anticoagulants that increase prothrombin time (PT) and INR. EXC#11
37. Main Study Period Any history of chronic kidney disease or kidney impairment defined by current or previous hemodialysis/hemofiltration; or an estimated glomerular filtration rate (eGFR) <75 mL/min/1.73 m2 at either Screening 1 or Screening 2 (using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation). (Based on central laboratory measurements; 1 repeat test is allowed). EXC#12
38. Main Study Period Urinary albumin to creatinine ratio ≥300 mg/g creatinine (≥33.9 mg/mmol creatinine) at Screening 1 (Based on central laboratory measurement; 1 repeat test is allowed for each screening visit). EXC#13
39. Main Study Period Presence of hepatitis B surface antigen (HBsAg) at Screening 1 or within 3 months prior to first dose of study intervention (Based on local or central laboratory measurements; 1 repeat test is allowed). EXC#14
40. Safety Lead-in Positive HIV antibody test at Screening 1 (central laboratory measurements; 1 repeat test is allowed). EXC#20
41. Main Study Period Positive hepatitis C antibody test result at Screening 1 or within 3 months prior to first dose of study intervention. Note: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative hepatitis C RNA test is obtained and provided treatment for HCV infection occurred 2 years or more prior to screening (Based on central laboratory measurements; 1 repeat test is allowed). EXC#15
42. Main Study Period Positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention. (Based on central laboratory measurements; 1 repeat test is allowed) Note: Test is optional and participants with negative hepatitis C antibody test are not required to also undergo hepatitis C RNA testing. EXC#16
43. Main Study Period Other primary causes of liver disease (including but not limited to primary biliary cholangitis, primary sclerosing cholangitis, 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. ALD or MetALD must be the primary cause of liver disease. EXC#17
44. Main Study Period Current, or history of known hepatocellular carcinoma (HCC). EXC#18
45. Safety Lead-in ALT or AST ≥250 U/L at either Screening 1 or Screening 2 (Based on central laboratory measurement; 1 repeat test is allowed for each screening visit). EXC#6
46. Main Study Period All organ transplant recipients, except for history of corneal transplants, or current listing or active consideration for listing for liver transplant during the screening period. EXC#19
47. Main Study Period Chronic or acute, including partial, known portal vein thrombosis. EXC#20
48. Main Study Period Prior transjugular intrahepatic portosystemic shunt (TIPSS) insertion. EXC#21
49. Main Study Period Positive HIV antibody test at Screening 1 (central laboratory measurements; 1 repeat test is allowed). EXC#22
50. Main Study Period Any acute cardiovascular event including myocardial infarction, unstable angina, symptomatic heart failure, or cerebrovascular accident in the 6 months prior to Screening 1. EXC#23
51. Main Study Period Poorly controlled hypertension defined as systolic blood pressure ≥160 mmHg and diastolic blood pressure ≥90 mmHg at both Screening 1 and Screening 2 despite standard medical management EXC#24
52. Safety Lead-in Presence of hepatitis B surface antigen (HBsAg) at Screening 1 or within 3 months prior to first dose of study intervention (Based on central or local laboratory measurements; 1 repeat test is allowed). EXC#11
53. Main Study Period BMI >35 kg/m2. EXC#25
54. Main Study Period HbA1≥9.5% (80.3 mmol/mol or 12.5 mmol/L) at screening visits 1 and 2. EXC#26
55. Main Study Period Any history of anaphylaxis or hypersensitivity to GSK4532990 or any of the constituents of the injection. EXC#27
56. Safety Lead-in Any acute cardiovascular event including myocardial infarction, unstable angina, symptomatic heart failure, or cerebrovascular accident in the 6 months prior to Screening 1. EXC#21
57. Main Study Period Current use of other GalNAc conjugated siRNA therapy. EXC#28
58. Main Study Period Previous use of other investigational therapies targeting HSD17B13 and/or PNPLA3. EXC#29
59. Main Study Period Prior investigational therapies unless beyond washout period of at least 5 half-lives or 6 weeks (whichever is longer) from Screening 1. EXC#30
60. Main Study Period Use of therapies known to induce steatohepatitis (e.g., methotrexate, tamoxifen, amiodarone, 5-fluorouracil) for more than 2 weeks in the year prior to D1. EXC#31
61. Main Study Period Recent major surgery within previous 6 weeks prior to D1. EXC#32
62. Main Study Period Current or ongoing malignancy (except for basal cell carcinoma or uterine carcinoma-in-situ) at Screening 1. Participants under evaluation for possible malignancy at Screening 1 are not eligible. EXC#33
63. Main Study Period Any symptomatic infection including COVID-19 during Screening. Participants may be eligible 2 weeks after resolution of symptoms. EXC#34
64. Safety Lead-in Positive hepatitis C antibody test result at Screening 1 or within 3 months prior to first dose of study intervention. Note: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative hepatitis C RNA test is obtained (Based on local or central laboratory measurements; 1 repeat test is allowed). EXC#12
65. Main Study Period Current or planned participation in any clinical trial of investigational therapies or medical devices. Participation in clinical trial of investigational software applications for the treatment of Alcohol Use Disorder is permitted. EXC#35
66. Main Study Period Clinical suspicion of rhabdomyolysis during the screening period. EXC#36
67. Safety Lead-in Poorly controlled hypertension defined as systolic blood pressure ≥160 mmHg and diastolic blood pressure ≥90 mmHg at both Screening 1 and Screening 2 despite standard medical management. EXC#22
68. Main Study Period Clinical suspicion of a bleeding episode during the screening period related to portal hypertension and/or low blood fibrinogen level. EXC#37
69. Main Study Period Any abnormality on a 12-lead ECG during the screening period that, in the opinion of the Investigator, compromises the participant’s safety in this study. EXC#38
70. Main Study Period Participants opting for the optional MRE assessment must not have any contraindication to undergoing Magnetic Resonance Elastography. EXC#39
71. Main Study Period Participants opting for liver biopsies must not have any contraindication to undergoing liver biopsy. Contraindications to undergoing liver biopsy include but are not limited to use of antiplatelet medications or a medical history of abnormal bleeding. Participants may be eligible if antiplatelet medications have been discontinued ≥5 half-lives prior to liver biopsy. Non-steroidal anti-inflammatory drugs (NSAIDs) must have been discontinued ≥3 days before biopsy and aspirin ≥3 days before biopsy. EXC#40
72. Specific exclusion criteria for COMP Clinically apparent ascites. EXC#42
73. Specific exclusion criteria for COMP CTP score ≥7 (Class B or C grade hepatic impairment) during Screening. EXC#43
74. Specific exclusion criteria for COMP Average MELD 3.0 score ≥12 using Screening 1 and Screening 2 results (Based on central laboratory measurement; 1 repeat test is allowed for each screening visit). EXC#44
75. Specific exclusion criteria for COMP Any liver-related clinical event (see Section 10.7) that started (onset) < 12 months prior to Baseline (D1). EXC#45
76. Safety Lead-in Meeting any definition of organ system failure as defined by the North American Consortium for Study of End-stage Liver Disease (NACSELD) (see 10.10.5). EXC#2
77. Specific exclusion criteria for DECOMP CTP Score ≥10 (Class C) during Screening. EXC#46
78. Safety Lead-in BMI >35 kg/m2 at Screening 1. EXC#23
79. Specific exclusion criteria for DECOMP Any liver-related clinical event (see Section 10.7) that started (onset) < 8 weeks prior to Baseline (D1). EXC#47
80. Specific exclusion criteria for DECOMP No previous liver-related clinical event or the most recent liver-related clinical event (see Section 10.7) started (onset) ≥12 months prior to Baseline (D1). EXC#48
81. Specific exclusion criteria for DECOMP Average MELD 3.0 score <15 using Screening 1 and Screening 2 results (Based on central laboratory measurement; 1 repeat test is allowed for each screening visit). EXC#49
82. Specific exclusion criteria for INTER Average MELD 3.0 score <12 using Screening 1 and Screening 2 results (Based on central laboratory measurement; 1 repeat test is allowed for each screening visit) EXC#50
83. Specific exclusion criteria for INTER Average MELD 3.0 score ≥15 using Screening 1 and Screening 2 results (Based on central laboratory measurement; 1 repeat test is allowed for each screening visit) EXC#51
84. Main Study Period Average of triplicate QTc >450 msec for males or QTc >470 msec for females or QTc >480 msec in participants with bundle branch block (1 repeat test is allowed). EXC#52
85. Safety Lead-in Average MELD pre-2016 score ≥ 22 using Screening 1 and Screening 2 results. (Based on central laboratory measurement; 1 repeat test is allowed for each screening visit). EXC#3
86. Specific exclusion criteria for COMP Clinically apparent ascites. EXC#42
87. Safety Lead-in Evidence of Wernicke-Korsakoff syndrome or alcohol-related dementia in the opinion of investigator. EXC#36
88. Specific exclusion criteria for INTER CTP Score ≥10 (Class C) during Screening. EXC#53
89. Safety Lead-in HbA1c ≥9.5% (80.3 mmol/mol or 12.5 mmol/L) at both Screening 1 and Screening 2. EXC#24
90. Specific exclusion criteria for INTER Any liver-related clinical event that started (onset) < 8 weeks prior to Baseline (D1). EXC#54
91. Main Study Period Evidence of Wernicke-Korsakoff syndrome or alcohol-related dementia in the opinion of investigator. EXC#41

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Safety Lead-in Incidence of AEs and of SAEs.
2. Safety Lead-in Incidence of potentially clinically relevant changes from baseline in ECG, vital signs, and clinical laboratory tests.
3. Main Study Period COMP cohort • Change from baseline in LSM using FibroScan® at Week 28, considering death, liver-related hospitalization, liver transplantation and HCC to be poor outcomes DECOMP cohort • Change from baseline in MELD score at Week 28, considering death, liver-related hospitalization, liver transplantation and HCC to be poor outcomes

Secondary endpoints 3

1. Safety Lead-in GSK4532990 plasma Cmax, AUC(0-t), AUC(0-24), t1/2, CL/F, tmax, and Vz/F following a single subcutaneous dose of GSK4532990.
2. Main Study Period COMP cohort • Change from baseline in LSM using FibroScan® at Weeks 4, 8, 12, 16, 20, and 24, considering death, liver-related hospitalization, liver transplantation and HCC to be poor outcomes DECOMP cohort • Change from baseline in MELD score at Weeks 4, 8, 12, 16, 20, and 24, considering death, liver-related hospitalization, liver transplantation and HCC to be poor outcomes
3. Main Study Period COMP cohort, INTER cohort, DECOMP cohort and POOLED In a subset of participants with intensive PK sampling, plasma exposure 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)

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 35

Locations

8 EU/EEA countries · 46 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 129 files

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

Application history

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