Last updated: 05/19/2026 10:00:15

Study of GSK3965193 in Healthy Participants and Participants Living with Chronic Hepatitis B Infection

GSK study ID
214760
See study documents
Clinicaltrials.gov ID
NCT05330455
See results summary
EudraCT ID
2021-005117-13
EU CT Number
2023-509684-24
Trial status
Terminated (halted prematurely)
Terminated (halted prematurely)
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: Four-part, Randomized, Double-blind (Parts 1, 2A, 3 and 4), Multi-center, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK3965193 Monotherapy in Healthy Participants and in Participants Living with Chronic Hepatitis B Infection; and GSK3965193 in Combination with Bepirovirsen in Participants Living with Chronic Hepatitis B Infection
Trial description: This Phase 1/2a multiple part study is a first time-in-human (FTIH) study designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of single (Part 1) and repeat doses (Part 2) of GSK3965193 in healthy participants. Part 3 will evaluate the ability of GSK3965193 to lower hepatitis B virus surface antigen (HBsAg) in participants living with chronic hepatitis B infection (PLWCHB) and will be given the option to subsequently receive treatment with open label bepirovirsen. Part 4 will evaluate the safety and tolerability of combination therapy with GSK3965193 and bepirovirsen and the potential to effect sustained virologic response in PLWCHB.
Primary purpose:
Treatment
Trial design:
Cross-over
Masking:
Triple (Participant, Care Provider, Investigator)
Allocation:
Randomized
Primary outcomes:

Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Treatment Emergent Adverse Events (STEAEs), and Treatment Withdrawals due to TEAEs

Timeframe: From the start of study intervention (Day 1) up to 12 weeks

Part 2A: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals due to TEAEs

Timeframe: From the start of study intervention (Day 1) up to 6 weeks

Part 2B: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals due to TEAEs

Timeframe: From the start of study intervention (Day 1) up to 9 weeks

Part 3: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals due to TEAEs

Timeframe: From the start of study intervention (Day 1) up to 6 weeks

Part 4: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals due to TEAEs

Timeframe: From the start of study intervention (Day 1) up to 48 weeks

Part 1: Number of Participants With Clinically Significant Hematology and Clinical Chemistry Parameters

Timeframe: At Day 2

Part 2A: Number of Participants With Clinically Significant Hematology, Clinical Chemistry, and Urinalysis Parameters

Timeframe: Up to 21 days

Part 2B: Number of Participants With Clinically Significant Hematology, Clinical Chemistry, and Urinalysis Parameters

Timeframe: Up to 9 weeks

Part 3: Number of Participants With Clinically Significant Hematology and Clinical Chemistry Parameters

Timeframe: Up to 35 days

Part 3: Number of Participants With Clinically Significant Urinalysis Parameters

Timeframe: Up to 28 days

Part 4: Number of Participants With Clinically Significant Hematology, Clinical Chemistry, and Urinalysis Parameters

Timeframe: Up to 48 weeks

Part 1: Number of Participants With Clinically Significant Vital Sign Findings

Timeframe: Up to 12 weeks

Part 2A: Number of Participants With Clinically Significant Vital Sign Findings

Timeframe: Up to 21 days

Part 2B: Number of Participants With Clinically Significant Vital Sign Findings

Timeframe: Up to 9 weeks

Part 3: Number of Participants With Clinically Significant Vital Sign Findings

Timeframe: Up to 35 days

Part 4: Number of Participants With Clinically Significant Vital Signs Findings

Timeframe: Up to 48 weeks

Part 1: Number of Participants With Clinically Significant Electrocardiogram [ECG] Findings

Timeframe: Up to 12 weeks

Part 2A: Number of Participants With Clinically Significant ECG Findings

Timeframe: Up to 21 days

Part 3: Number of Participants With Clinically Significant ECG Findings

Timeframe: Up to 35 days

Part 4: Number of Participants With Clinically Significant ECG Findings

Timeframe: Up to 25 weeks

Part 2A: Number of Participants With Changes in Sensory Nerve Conduction at Day 7

Timeframe: Baseline and Day 7

Part 2A: Number of Participants With Changes in Sensory Nerve Conduction at Day 14

Timeframe: Baseline and Day 14

Part 2A: Number of Participants With Changes in Sensory Nerve Conduction at Day 42

Timeframe: Baseline and Day 42

Part 3: Number of Participants With Changes in Sensory Nerve Conduction at Day 15

Timeframe: Baseline and Day 15

Part 3: Number of Participants With Changes in Sensory Nerve Conduction at Day 29

Timeframe: Baseline and Day 29

Part 4: Number of Participants With Changes in Sensory Nerve Conduction

Timeframe: Baseline up to 29 days

Part 1: Area Under the Concentration-time Curve (AUC) from Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3965193 Following Single Dose Administration

Timeframe: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours (h) post-dose

Part 2A: AUC over the Dosing Interval Tau (AUC[0-tau]) of GSK3965193 Following Repeat Dose Administration

Timeframe: Pre-dose and 15 minutes (min), 30 min, 1 h, 2 h, 3 h, 4, h, 8 h, and 12 h post-first dose on Day 1; pre-dose and 15 min, 30 min, 1 h, 2h, 4 h, 8 h, and 12 h post-first dose on Day 14

Part 1: Maximum Observed Concentration (Cmax) of GSK3965193 Following Single Dose Administration

Timeframe: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post-dose

Part 2A: Cmax of GSK3965193 Following Repeat Dose Administration

Timeframe: Pre-dose and 15 min, 30 min, 1 h, 2 h, 3 h, 4, h, 8 h, and 12 h post-first dose on Day 1; pre-morning dose on Days 2 through 6 and Days 12 through 13; pre-dose and 15 min, 30 min, 1 h, 2h, 4 h, 8 h, 12 h, 24 h, 48 h, and 72 h post-first dose on Day 14

Part 1: Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK3965193 Following Single Dose Administration

Timeframe: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post-dose

Part 2A: Tmax of GSK3965193 Following Repeat Dose Administration

Timeframe: Pre-dose and 15 min, 30 min, 1 h, 2 h, 3 h, 4, h, 8 h, and 12 h post-first dose on Day 1; pre-morning dose on Days 2 through 6 and Days 12 through 13; pre-dose and 15 min, 30 min, 1 h, 2h, 4 h, 8 h, 12 h, 24 h, 48 h, and 72 h post-first dose on Day 14

Part 1: Apparent Terminal Half-life (T1/2) of GSK3965193 Following Single Dose Administration

Timeframe: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post-dose

Part 2A: T1/2 of GSK3965193 Following Repeat Dose Administration

Timeframe: Pre-dose and 15 min, 30 min, 1 h, 2 h, 3 h, 4, h, 8 h, and 12 h post-first dose on Day 1; pre-morning dose on Days 2 through 6 and Days 12 through 13; pre-dose and 15 min, 30 min, 1 h, 2h, 4 h, 8 h, 12 h, 24 h, 48 h, and 72 h post-first dose on Day 14

Part 3: Maximum Reduction of Serum HBsAg Levels from Baseline

Timeframe: From Baseline (Pre-dose on Day 1) up to 6 weeks

Part 4: Number of Participants Achieving Complete Response

Timeframe: Up to 48 weeks

Secondary outcomes:

Part 2B: AUC(0-inf) of GSK3965193 Following Single Dose Administration

Timeframe: Pre-dose and 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 48 h, and 72 h post-dose

Part 2B: Cmax of GSK3965193 Following Single Dose Administration

Timeframe: Pre-dose and 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 48 h, and 72 h post-dose

Part 3: AUC(0-tau) of GSK3965193 Following Repeat Dose Administration

Timeframe: Pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 1; pre-dose on Day 4, Day 8, Day 11, Day 15, Day 22; pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 28

Part 3: Cmax of GSK3965193 Following Repeat Dose Administration

Timeframe: Pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 1; pre-dose on Day 4, Day 8, Day 11, Day 15, Day 22; pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 28

Part 3: Tmax of GSK3965193 Following Repeat Dose Administration

Timeframe: Pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 1; pre-dose on Day 4, Day 8, Day 11, Day 15, Day 22; pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 28

Part 3: T1/2 of GSK3965193 Following Repeat Dose Administration

Timeframe: Pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 1; pre-dose on Day 4, Day 8, Day 11, Day 15, Day 22; pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 28

Part 3: Number of Participants With Greater than or Equal to [≥] 0.5 Times Log International Units per Milliliters [IU/mL] Reduction from Baseline in Serum HBsAg Levels

Timeframe: From Baseline (Day 1) up to 42 days

Part 3: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals due to TEAEs Among Participants Opting for Optional Bepirovirsen Treatment

Timeframe: From the start of study intervention up to 54 weeks

Part 3: Number of Participants With Clinically Significant Hematology, Clinical Chemistry, and Urinalysis Parameters Among Participants Opting for Optional Bepirovirsen Treatment

Timeframe: From Week 7 up to 54 weeks

Part 3: Number of Participants With Clinically Significant Vital Signs Among Participants Opting for Optional Bepirovirsen Treatment

Timeframe: From Week 7 up to 54 weeks

Part 4: Number of Participants With HBsAg Loss

Timeframe: Up to 48 weeks

Interventions:
Drug: GSK3965193
Drug: Placebo to match GSK3965193
Drug: Bepirovirsen
Enrollment:
74
Observational study model:
Not applicable
Primary completion date:
2025-19-05
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Hepatitis B
Product
Not applicable
Collaborators
Not applicable
Study date(s)
April 2022 to April 2026
Type
Interventional
Phase
1/2

Participation criteria

Sex
Female & Male
Age
18 - 65 Years
Accepts healthy volunteers
Yes
  • Parts 1 and 2: Participants between 18 and 55 years of age inclusive, at the time of signing the informed consent.
  • Parts 3 and 4: Participants between 18 and 65 years of age inclusive, at the time of signing the informed consent.
  • Exclusion Criteria for Healthy Participants:
  • Positive Hepatitis A virus antibody (HAV Ab immunoglobulin M [IgM]), or positive for HBV, hepatitis C virus (HCV) or human immunodeficiency virus (HIV) at screening
Inclusion and exclusion criteria
Inclusion criteria:
  • Parts 1 and 2: Participants between 18 and 55 years of age inclusive, at the time of signing the informed consent.
  • Parts 3 and 4: Participants between 18 and 65 years of age inclusive, at the time of signing the informed consent.
  • Body weight >=50 kilograms (kg) and body mass index within the range 18-32 kilograms per square meter (kg/m^2) (inclusive).
  • Male or female participant: a. Parts 1 and 2: woman of nonchildbearing potential only. b. Parts 3 and 4: woman of nonchildbearing potential or woman of child-bearing potential who is not pregnant or breastfeeding and is using a contraceptive method that is highly effective.
  • Capable of giving signed informed consent.
  • Additional Inclusion Criteria for PLWCHB (Parts 3 and 4).
  • Participants who have documented chronic hepatitis B virus (HBV) infection >=6 months prior to screening.
  • Participants currently receiving stable NA therapy (e.g., tenofovir disoproxil, tenofovir alafenamide, entecavir).
  • Plasma or serum HBsAg concentration >100 IU/mL.
  • Plasma or serum HBV deoxyribonucleic acid (DNA) concentration <90 IU/mL.
  • Hepatitis B virus e-antigen (HBeAg) positive or negative.
  • Alanine aminotransferase (ALT) <=2 times the upper limit of normal (ULN)
Exclusion criteria:
  • Exclusion Criteria for Healthy Participants:
  • Positive Hepatitis A virus antibody (HAV Ab immunoglobulin M [IgM]), or positive for HBV, hepatitis C virus (HCV) or human immunodeficiency virus (HIV) at screening
  • A current diagnosis of migraine headache
  • ALT >1 times ULN.
  • Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent [%])
  • Corrected QT interval (QTc) >450 milliseconds (msec)
  • Signs and symptoms suggestive of Coronavirus Disease 2019 (COVID-19)
  • Participants with known COVID-19 positive contacts in the past 14 days.
  • For participants in Part 2A: i. Personal history or family history of peripheral neuropathy. ii. A score ≥4 on the Toronto clinical scoring system for polyneuropathy
  • Current or previous use of tobacco- or nicotine-containing products (for example (e.g.) cigarettes, nicotine patches or electronic devices) within 6 months before screening and/or have a smoking pack history of >5 pack years Exclusion Criteria for PLWCHB:
  • Clinically significant abnormalities affecting physical or mental health in medical history or on physical examination, aside from chronic HBV infection.
  • Co-infection with or past history of HCV, HIV or Hepatitis D virus (HDV).
  • History of or suspected liver cirrhosis and/or evidence of cirrhosis.
  • Diagnosed or suspected hepatocellular carcinoma.
  • History of malignancy within the past 5 years with the exception of specific cancers that are cured by surgical resection (e.g., skin cancer).
  • History of vasculitis or presence of symptoms and signs of potential vasculitis [e.g., vasculitic rash, skin ulceration, repeated blood detected in urine without identified cause] or history/presence of other diseases Exclusion Criteria for Healthy Participants:
  • Positive Hepatitis A virus antibody (HAV Ab immunoglobulin M [IgM]), or positive for HBV, hepatitis C virus (HCV) or human immunodeficiency virus (HIV) at screening.
  • A current diagnosis of migraine headache
  • ALT >1 times ULN.
  • Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent [%]).
  • Corrected QT interval (QTc) >450 milliseconds (msec).
  • Signs and symptoms suggestive of Coronavirus Disease 2019 (COVID-19).
  • Participants with known COVID-19 positive contacts in the past 14 days.
  • For participants in Part 2A: i. Personal history or family history of peripheral neuropathy. ii. A score ≥4 on the Toronto clinical scoring system for polyneuropathy.
  • Current or previous use of tobacco- or nicotine-containing products (for example (e.g.) cigarettes, nicotine patches or electronic devices) within 6 months before screening and/or have a smoking pack history of >5 pack years Exclusion Criteria for PLWCHB:
  • Clinically significant abnormalities affecting physical or mental health in medical history or on physical examination, aside from chronic HBV infection.
  • Co-infection with or past history of HCV, HIV or Hepatitis D virus (HDV).
  • History of or suspected liver cirrhosis and/or evidence of cirrhosis.
  • Diagnosed or suspected hepatocellular carcinoma.
  • History of malignancy within the past 5 years with the exception of specific cancers that are cured by surgical resection (e.g., skin cancer).
  • History of vasculitis or presence of symptoms and signs of potential vasculitis [e.g., vasculitic rash, skin ulceration, repeated blood detected in urine without identified cause] or history/presence of other diseases that may be associated with vasculitis condition (e.g., systemic lupus erythematosus, rheumatoid arthritis, relapsing polychondritis, mononeuritis multiplex).
  • History of extrahepatic disorders possibly related to HBV immune conditions (e.g., nephrotic syndrome, any type of glomerulonephritis, polyarteritis nodosa, cryoglobulinaemia, uncontrolled hypertension).
  • History of alcohol or drug abuse/dependence: a. Current alcohol use as judged by investigator to potentially interfere with participant compliance. b. History of or current drug abuse/dependence as judged by the investigator to potentially interfere with participant compliance.
  • History or other evidence of bleeding from esophageal varices.
  • Documented history or other evidence of metabolic liver disease within 1 year of randomization.
  • Personal history or family history of peripheral neuropathy.
  • A score >4 on the Toronto clinical scoring system for polyneuropathy.
  • History of having received or currently receiving any systemic anti-neoplastic (including radiation) or immune-modulatory treatment (including systemic oral corticosteroids, interferon or pegylated interferon) within the 3 months prior to randomization or the expectation that such treatment will be needed at any time during the study.
  • Abnormal and clinically significant 12-lead ECG finding.
  • Currently taking, or taken within 3 months prior to randomization, any immunosuppressing drugs (e.g., prednisone), other than a short course of therapy (≤2 weeks) or topical/inhaled steroid use.
  • Participants requiring anti-coagulation therapies.
  • Prior treatment with any oligonucleotide or small interfering RNA (siRNA) within 12 months prior to the first dosing day.
  • Positive test for COVID-19 infection.

Trial location(s)

Location
Status
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Location
GSK Investigational Site
Cambridge, Unmapped, CB2 2GG
Status
Study Complete
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Location
GSK Investigational Site
Calgary, AB, Canada, T2N 4Z6
Status
Study Complete
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Location
GSK Investigational Site
Monza MB, Italy, 20900
Status
Study Complete
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Location
GSK Investigational Site
Daegu, Unmapped, 41944
Status
Study Complete
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Location
GSK Investigational Site
Pusan, Unmapped, 49241
Status
Study Complete
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Location
GSK Investigational Site
London, Unmapped, SE5 9RS
Status
Terminated/Withdrawn
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Location
GSK Investigational Site
Milano, Italy, 20122
Status
Study Complete
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Location
GSK Investigational Site
Nantes cedex 1, France, 44000
Status
Study Complete
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Location
GSK Investigational Site
Ottawa, ON, Canada, K1H 8L6
Status
Study Complete
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Location
GSK Investigational Site
Seoul, Unmapped, 05505
Status
Study Complete
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Location
GSK Investigational Site
London, Unmapped, SW17 0QT
Status
Study Complete
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Location
GSK Investigational Site
GRENOBLE CEDEX 9, France, 38043
Status
Study Complete
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Location
GSK Investigational Site
London, Unmapped, W2 1NY
Status
Study Complete
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Location
GSK Investigational Site
Lyon, France, 69004
Status
Terminated/Withdrawn
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Location
GSK Investigational Site
Rennes, France, 35033
Status
Study Complete
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Location
GSK Investigational Site
Bangkok, Thailand, 10330
Status
Study Complete
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Study documents

Protocol
Available language(s): English
Download document(s)
Statistical analysis plan
Available language(s): English
Download document(s)

If you wish to request for full study report, please contact - [email protected]

Results overview

Results posted on ClinicalTrials.gov

Recruitment status
Terminated (halted prematurely)
Actual primary completion date
2025-19-05
Actual study completion date
2026-08-04

Plain language summaries

Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

Additional information about the trial

Additional information
Not applicable
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