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

Study at a glance

From the registry record, last updated by the sponsor on 14 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

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

ClinicalTrials.gov ID

NCT05330455

Acronym / sponsor ID

214760

Conditions

Hepatitis B

Keywords

Bepirovirsen, Chronic hepatitis B, First-time-in-human, GSK3965193

Phase

Phase 1/2

Study type

Interventional

Recruitment status

TerminatedReason stopped: The study was terminated as a strategic decision

Enrolment

74 participants (actual)

Lead sponsor

GlaxoSmithKlineIndustry (pharma, biotech, devices)

Study start

14 Apr 2022 (actual)

Primary completion

19 May 2025 (actual)

Study completion

8 Apr 2026 (actual)

First posted

15 Apr 2022 (actual)

Results

Posted 16 Jun 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Randomised

Intervention model

Crossover

Masking

Triple blind (participant, care provider, investigator)

Number of arms

18

Model description

Parts 1 and Part 2B are crossover and Part 2A, Part 3 and Part 4 are parallel group

Who may qualify

Ages

18 to 65 years

Sex

All

Healthy volunteers

Accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

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

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

   An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator. An AE was considered treatment emergent if the AE onset date was on or after study intervention start date (i.e., Day 1) till Day 5 after study intervention administration. Any AE which started post Day 5 of study intervention administration was not considered as TEAE.

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

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

   An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator. An AE was considered treatment emergent if the AE onset date was on or after study intervention start date.

3. Part 2B: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals Due to TEAEs

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

   An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator. An AE was considered treatment emergent if the AE onset date was on or after study intervention start date (i.e., Day 1) till Day 5 after study intervention administration. Any AE which started post Day 5 of study intervention administration was not considered as TEAE.

4. Part 3: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals Due to TEAEs

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

   An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator. An AE was considered treatment emergent if the AE onset or worsen date was on or after study intervention start date. Data for the placebo or GSK3965193 monotherapy phase were presented.

5. Part 4: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals Due to TEAEs

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

   An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator. An AE would be considered treatment emergent if the AE onset or worsen date was on or after study intervention start date.

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

   Time frame: At Day 2

   Blood samples were collected to analyze hematology and clinical chemistry parameters: platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, RBC indices (mean corpuscular volume [MCV] and mean corpuscular hemoglobin [MCH]), white blood cell (WBC) count with differential (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), blood urea nitrogen (BUN), creatinine, glucose (non-fasting), potassium, sodium, calcium, aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT), alkaline phosphatase, total bilirubin, indirect bilirubin, direct bilirubin, total protein, and albumin. Clinical significance of laboratory parameters was determined by the investigator.

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

   Time frame: Up to 21 days

   Blood samples were collected to analyze hematology and clinical chemistry parameters: platelet count, RBC count, hemoglobin, hematocrit, RBC indices (MCV and MCH), WBC count with differential (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), BUN, creatinine, glucose (non-fasting), potassium, sodium, calcium, AST/SGOT, ALT/SGPT, alkaline phosphatase, total bilirubin, indirect bilirubin, direct bilirubin, total protein, and albumin. Urine samples were analyzed using automated urinalysis or urine dipstick. Microscopic examination was performed if abnormal blood or protein was present in the urine sample. Clinical significance of laboratory parameters was determined by the investigator.

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

   Time frame: Up to 9 weeks

   Blood samples were collected to analyze hematology and clinical chemistry parameters: platelet count, RBC count, hemoglobin, hematocrit, RBC indices (MCV and MCH), WBC count with differential (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), BUN, creatinine, glucose (non-fasting), potassium, sodium, calcium, AST/SGOT, ALT/SGPT, alkaline phosphatase, total bilirubin, indirect bilirubin, direct bilirubin, total protein, and albumin. Urine samples were analyzed using automated urinalysis or urine dipstick. Microscopic examination was performed if abnormal blood or protein was present in the urine sample. Clinical significance of laboratory parameters was determined by the investigator.

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

   Time frame: Up to 35 days

   Blood samples were collected to analyze hematology and clinical chemistry parameters: platelet count, RBC count, hemoglobin, hematocrit, RBC indices (MCV and MCH), WBC count with differential (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), BUN, creatinine, glucose (non-fasting), potassium, sodium, calcium, AST/SGOT, ALT/SGPT, alkaline phosphatase, total bilirubin, indirect bilirubin, direct bilirubin, total protein, and albumin. Clinical significance of laboratory parameters was determined by the investigator. Data for the placebo or GSK3965193 monotherapy phase were presented.

10. Part 3: Number of Participants With Clinically Significant Urinalysis Parameters

    Time frame: Up to 28 days

    Urine samples were analyzed using automated urinalysis or urine dipstick. Microscopic examination was performed if abnormal blood or protein was present in the urine sample. Clinical significance of laboratory parameters was determined by the investigator. Data for the placebo or GSK3965193 monotherapy phase were presented.

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

    Time frame: Up to 48 weeks

    Blood samples were planned to be collected to analyze hematology and clinical chemistry parameters: platelet count, RBC count, hemoglobin, hematocrit, RBC indices (MCV and MCH), WBC count with differential (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), BUN, creatinine, glucose (non-fasting), potassium, sodium, calcium, AST/SGOT, ALT/SGPT, alkaline phosphatase, total bilirubin, indirect bilirubin, direct bilirubin, total protein, and albumin. Urine samples were planned to be analyzed using automated urinalysis or urine dipstick. Microscopic examination was planned to be performed if abnormal blood or protein was present in the urine sample. Clinical significance of laboratory parameters would be determined by the investigator.

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

    Time frame: Up to 12 weeks

    Vital signs included systolic blood pressure (SBP) and diastolic blood pressure (DBP), pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of the vital sign findings was determined by the investigator.

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

    Time frame: Up to 21 days

    Vital signs included SBP and DBP, pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of the vital sign findings was determined by the investigator.

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

    Time frame: Up to 9 weeks

    Vital signs included SBP and DBP, pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of the vital sign findings was determined by the investigator.

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

    Time frame: Up to 35 days

    Vital signs included temperature, SBP and DBP, pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of the vital sign findings was determined by the investigator. Data for the placebo or GSK3965193 monotherapy phase were presented.

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

    Time frame: Up to 48 weeks

    Vital signs were planned to include temperature, SBP and DBP, pulse and respiratory rate and were planned to be measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of the vital sign findings would be determined by the investigator.

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

    Time frame: Up to 12 weeks

    A 12-lead ECG was recorded with the participant in a semi-supine position after 5 minutes of rest using an ECG machine. The parameters collected were PR, QRS, QT, and corrected QT (QTc) intervals. Clinical significance of ECG parameters was determined by the investigator.

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

    Time frame: Up to 21 days

    A 12-lead ECG was recorded with the participant in a semi-supine position after 5 minutes of rest using an ECG machine. The parameters collected were PR, QRS, QT, and QTc intervals. Clinical significance of ECG parameters was determined by the investigator.

19. Part 3: Number of Participants With Clinically Significant ECG Findings

    Time frame: Up to 35 days

    A 12-lead ECG was recorded with the participant in a semi-supine position after 5 minutes of rest using an ECG machine. The parameters collected were PR, QRS, QT, and QTc intervals. Clinical significance of ECG parameters was determined by the investigator. Data for the placebo or GSK3965193 monotherapy phase were presented.

20. Part 4: Number of Participants With Clinically Significant ECG Findings

    Time frame: Up to 25 weeks

    A 12-lead ECG was planned to be recorded with the participant in a semi-supine position after 5 minutes of rest using an ECG machine. The parameters planned to be collected were PR, QRS, QT, and QTc intervals. Clinical significance of ECG findings would be determined by the investigator.

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

    Time frame: Baseline and Day 7

    Sensory nerve conduction testing was performed to detect neuropathy in participants. Nerve conduction velocity (NCV) and nerve conduction amplitude were determined. Sensory nerve conduction studies at Baseline were collected twice, one at the time of screen and one prior to dosing. Mean (arithmetic mean) of two measurements were considered as Baseline. Number of participants with 25 percent (%) decrease in NCV and 50% decrease in nerve conduction amplitude from Baseline at Day 7 was reported.

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

    Time frame: Baseline and Day 14

    Sensory nerve conduction testing was performed to detect neuropathy in participants. NCV and nerve conduction amplitude were determined. Sensory nerve conduction studies at Baseline were collected twice, one at the time of screen and one prior to dosing. Mean (arithmetic mean) of two measurements were considered as Baseline. Number of participants with 25% decrease in NCV and 50% decrease in nerve conduction amplitude from Baseline at Day 14 was reported.

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

    Time frame: Baseline and Day 42

    Sensory nerve conduction testing was performed to detect neuropathy in participants. NCV and nerve conduction amplitude were determined. Sensory nerve conduction studies at Baseline were collected twice, one at the time of screen and one prior to dosing. Mean (arithmetic mean) of two measurements were considered as Baseline. Number of participants with 25% decrease in NCV and 50% decrease in nerve conduction amplitude from Baseline at Day 42 was reported.

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

    Time frame: Baseline and Day 15

    Sensory nerve conduction testing was performed to detect neuropathy in participants. NCV and nerve conduction amplitude were determined. The best measurement out of Screening and Day -1 was considered as Baseline, best being the higher measurement. Number of participants with 25% decrease in NCV and 50% decrease in nerve conduction amplitude from Baseline at Day 15 for the placebo or GSK3965193 monotherapy phase was reported.

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

    Time frame: Baseline and Day 29

    Sensory nerve conduction testing was performed to detect neuropathy in participants. NCV and nerve conduction amplitude were determined. The best measurement out of Screening and Day -1 was considered as Baseline, best being the higher measurement. Number of participants with 25% decrease in NCV and 50% decrease in nerve conduction amplitude from Baseline at Day 29 for the placebo or GSK3965193 monotherapy phase was reported.

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

    Time frame: Baseline up to 29 days

    Sensory nerve conduction testing was planned to be performed to detect neuropathy in participants. NCV and nerve conduction amplitude were planned to be determined. Number of participants with 25% decrease in NCV and 50% decrease in nerve conduction amplitude from baseline was planned to be reported.

27. 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

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

    Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.

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

    Time frame: 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

    Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods. As the dosing interval Tau was 12 hours, AUC(0-tau) is the same as AUC from time zero to 12 hours after dosing (AUC[0-12]).

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

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

    Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.

30. Part 2A: Cmax of GSK3965193 Following Repeat Dose Administration

    Time frame: 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

    Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.

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

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

    Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.

32. Part 2A: Tmax of GSK3965193 Following Repeat Dose Administration

    Time frame: 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

    Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.

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

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

    Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.

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

    Time frame: 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

    Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.

35. Part 3: Maximum Reduction of Serum HBsAg Levels From Baseline

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

    Blood samples were collected from participants to assess HBsAg levels for the placebo or GSK3965193 monotherapy phase. Baseline was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Posterior mean and associated 95 percent (%) credible interval were derived for maximum reduction of serum HBsAg levels from Baseline using Bayesian mixed model repeated measures. The data presented are mean referring to posterior mean, with 95% confidence interval referring to 95% credible interval.

36. Part 4: Number of Participants Achieving Complete Response

    Time frame: Up to 48 weeks

    Blood samples were planned to be collected to assess HBsAg and hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Complete response is defined HBsAg and HBV DNA below lower limit of quantification (LLOQ) for 6 consecutive months after the planned end of treatment.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2026.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

14 sites in 6 countries: see every site and its status.