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

Primary Purpose

Hepatitis B

Status
Recruiting
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
GSK3965193
Placebo to match GSK3965193
Bepirovirsen
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis B focused on measuring Bepirovirsen, Chronic hepatitis B, First-time-in-human, GSK3965193

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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 non-childbearing potential only. b. Parts 3 and 4: woman of non-childbearing 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.
  • 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 in medical history, 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 8 weeks prior to the first dose of study drug 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 of screening, 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.
  • Participants with known COVID-19 positive contacts in the past 14 days.

Sites / Locations

  • GSK Investigational SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Part 1 Cohort 1: GSK3965193 and placebo

Part 1 Cohort 2: GSK3965193 and placebo

Part 2A Cohort 3: GSK3965193 or placebo

Part 2A Cohort 4: GSK3965193 or placebo

Part 2A Cohort 5: GSK3965193 or placebo

Part 2B Cohort 6: GSK3965193

Part 3 Cohort 7: GSK3965193 or placebo

Part 4 Cohort 8: GSK3965193 and bepirovirsen or placebo and bepirovirsen

Arm Description

Healthy participants will be randomized to receive single ascending doses of GSK3965193 and placebo in one of 4 treatment sequences in a 3:1 ratio in fasted conditions. In period 1, participants will receive GSK3965193 (Dose 1) + Placebo; in period 2: GSK3965193 (Dose 2) + Placebo; in period 3: GSK3965193 (Dose 3) + Placebo and in period 4: GSK3965193 (Dose 4) + Placebo. There will be a minimum of 7 days washout between dosing in each treatment period.

Healthy participants will be randomized to receive single ascending doses of GSK3965193 and placebo in one of 4 treatment sequences in a 3:1 ratio in fasted conditions. In period 1, participants will receive GSK3965193 (Dose 5) + Placebo; in period 2: GSK3965193 (Dose 6) + Placebo; in period 3: GSK3965193 (Dose 7) + Placebo and in period 4: GSK3965193 (Dose 8) + Placebo. There will be a minimum of 7 days washout between dosing in each period.

Healthy participants will be randomized 3:1 to receive repeat doses of either GSK3965193 (Dose X) or placebo under fasted conditions. Part 2A may start while Part 1 is still ongoing. The starting dose in Part 2 will be at least 3-fold below the highest dose completed in Part 1.

Healthy participants will be randomized 3:1 to receive repeat doses either GSK3965193 (Dose Y) or placebo under fasted conditions. Part 2A may start while Part 1 is still ongoing. The starting dose in Part 2 will be at least 3-fold below the highest dose completed in Part 1.

Healthy participants will be randomized 3:1 to receive repeat doses either GSK3965193 (Dose Z) or placebo under fasted conditions. Part 2A may start while Part 1 is still ongoing. The starting dose in Part 2 will be at least 3-fold below the highest dose completed in Part 1.

Healthy Participants will be randomized 1:1 to receive single doses of GSK3965193 (Dose A) under fasted and fed conditions in treatment period 1. In period 2, the participants who received GSK3965193 (Dose A) under fasted conditions in treatment period 1 will receive the same dose under fed conditions, and vice versa. In the third period, all participants will receive a single dose of GSK3965193 (Dose B) different strength under fasted conditions. The dose level for the third period will be selected based on the results of the first two periods. There will be a minimum of 7 days washout between dosing in each treatment period.

PLWCHB on stable nucleos(t)ide analog (NA) therapy will be randomized 3:1 to receive repeat dose of either GSK3965193 (Dose E) or placebo. This part will commence after completion of both Part 1 and Part 2.

PLWCHB participants on stable NA therapy who have not participated in Part 3 of the study will be randomized 3:1 to receive repeat dose either GSK3965193 or placebo. In addition, all participants in this cohort will also receive bepirovirsen. This part will commence after completion of Part 3, contingent on the clinical safety and efficacy data from Part 3.

Outcomes

Primary Outcome Measures

Parts 1 and 2B: Number of participants with adverse events (AEs), serious adverse events (SAEs), and withdrawals due to AEs
Part 2A: Number of participants with AEs, SAEs, and withdrawals due to AEs
Parts 1 and 2B: Number of participants with clinically significant changes in laboratory parameters
Parts 1 and 2B: Number of participants with clinically significant changes in vital signs and cardiac parameters (electrocardiogram [ECG])
Part 2A: Number of participants with clinically significant changes in laboratory parameters, vital signs, cardiac parameters (ECG)
Part 2A: Number of participants with clinically significant nerve changes
Part 1 and 2B: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-inf]) of GSK3965193 following single dose administration
Part 2A: AUC(0-tau) of GSK3965193 following repeat dose administration
Part 1 and 2B: maximum observed concentration (Cmax) of GSK3965193 following single dose administration
Part 2A: Cmax of GSK3965193 following repeat dose administration
Part 1 and 2B: Time to maximum observed plasma drug concentration (Tmax) of GSK3965193 following single dose administration
Part 2A: Tmax of GSK3965193 following repeat dose administration
Part 1 and 2B: Apparent terminal half-life (T1/2) of GSK3965193 following single dose administration
Part 2A: T1/2 of GSK3965193 following repeat dose administration
Part 3: Number of participants with AEs, SAEs, and withdrawals due to AEs
Part 4: Number of participants with AEs, SAEs, and withdrawals due to AEs
Part 3: Number of participants with clinically significant changes in laboratory parameters and vital signs
Part 3: Number of participants with clinically significant changes in cardiac parameters (ECG)
Part 4: Number of participants with clinically significant changes in laboratory parameters and vital signs
Part 4: Number of participants with clinically significant changes in cardiac parameters (ECG)
Part 3: Number of participants with clinically significant nerve changes
Part 4: Number of participants with clinically significant nerve changes
Part 3: Change from Baseline in HBsAg levels
Part 4 : Number of participants achieving sustained virologic response
Parts 1 and 2B: Number of participants with. adverse events (AEs), serious adverse events. (SAEs), and withdrawals due to AEs
Parts 1 and 2B: Number of participants with. clinically significant changes in laboratory. parameters
Parts 1 and 2B: Number of participants with. clinically significant changes in vital signs and. cardiac parameters (electrocardiogram [ECG])
Part 2A: Number of participants with clinically. significant changes in laboratory parameters, vital signs, cardiac parameters (ECG)
Part 2A: Number of participants with clinically. significant nerve changes
Part 2A: T1/2 of GSK3965193 following repeat. dose administration
Part 3: Number of participants with clinically. significant changes in laboratory parameters and vital signs
Part 3: Number of participants with clinically. significant changes in cardiac parameters (ECG)
Part 4: Number of participants with clinically. significant changes in laboratory parameters and vital signs
Part 4: Number of participants with clinically. significant changes in cardiac parameters (ECG)
Part 3: Number of participants with clinically. significant nerve changes
Part 4: Number of participants with clinically. significant nerve changes
Part 3: Maximum reduction of serum HBsAg levels from Baseline
Part 4: Number of participants achieving. sustained virologic response

Secondary Outcome Measures

Part 2B: AUC(0-inf) of GSK3965193 following single dose administration
Part 2B: Cmax of GSK3965193 following single dose administration
Part 3: AUC(0-tau) of GSK3965193 following repeat dose administration
Part 3: Cmax of GSK3965193 following repeat dose administration
Part 3: Tmax of GSK3965193 following repeat dose administration
Part 3: T1/2 of GSK3965193 following repeat dose administration
Part 3: Change from Baseline in HBsAg levels (greater than or equal to [>=] 0.5 times log international units per milliliters [IU/mL])
Part 4: Number of participants with HBsAg loss
Part 2B: AUC (0-inf) of GSK3965193 following. single dose administration
Part 2B: Cmax of GSK3965193 following single. dose administration
Part 3: AUC(0-tau) of GSK3965193 following. repeat dose administration
Part 3: Tmax of GSK3965193 following repeat. dose administration
Part 3: T1/2 of GSK3965193 following repeat. dose administration
Part 3: Change from baseline in serum HBsAg levels from baseline. (greater than or equal to [≥] 0.5 times log. international units per milliliters [IU/mL])
Number of participants with HBsAg loss

Full Information

First Posted
April 8, 2022
Last Updated
June 22, 2023
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT05330455
Brief Title
Study of GSK3965193 in Healthy Participants and Participants Living With Chronic Hepatitis B Infection
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 14, 2022 (Actual)
Primary Completion Date
January 1, 2026 (Anticipated)
Study Completion Date
January 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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). 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B
Keywords
Bepirovirsen, Chronic hepatitis B, First-time-in-human, GSK3965193

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Model Description
Parts 1 and Part 2B are crossover and Part 2A, Part 3 and Part 4 are parallel group
Masking
ParticipantCare ProviderInvestigator
Masking Description
This is a double-blind study
Allocation
Randomized
Enrollment
132 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part 1 Cohort 1: GSK3965193 and placebo
Arm Type
Experimental
Arm Description
Healthy participants will be randomized to receive single ascending doses of GSK3965193 and placebo in one of 4 treatment sequences in a 3:1 ratio in fasted conditions. In period 1, participants will receive GSK3965193 (Dose 1) + Placebo; in period 2: GSK3965193 (Dose 2) + Placebo; in period 3: GSK3965193 (Dose 3) + Placebo and in period 4: GSK3965193 (Dose 4) + Placebo. There will be a minimum of 7 days washout between dosing in each treatment period.
Arm Title
Part 1 Cohort 2: GSK3965193 and placebo
Arm Type
Experimental
Arm Description
Healthy participants will be randomized to receive single ascending doses of GSK3965193 and placebo in one of 4 treatment sequences in a 3:1 ratio in fasted conditions. In period 1, participants will receive GSK3965193 (Dose 5) + Placebo; in period 2: GSK3965193 (Dose 6) + Placebo; in period 3: GSK3965193 (Dose 7) + Placebo and in period 4: GSK3965193 (Dose 8) + Placebo. There will be a minimum of 7 days washout between dosing in each period.
Arm Title
Part 2A Cohort 3: GSK3965193 or placebo
Arm Type
Experimental
Arm Description
Healthy participants will be randomized 3:1 to receive repeat doses of either GSK3965193 (Dose X) or placebo under fasted conditions. Part 2A may start while Part 1 is still ongoing. The starting dose in Part 2 will be at least 3-fold below the highest dose completed in Part 1.
Arm Title
Part 2A Cohort 4: GSK3965193 or placebo
Arm Type
Experimental
Arm Description
Healthy participants will be randomized 3:1 to receive repeat doses either GSK3965193 (Dose Y) or placebo under fasted conditions. Part 2A may start while Part 1 is still ongoing. The starting dose in Part 2 will be at least 3-fold below the highest dose completed in Part 1.
Arm Title
Part 2A Cohort 5: GSK3965193 or placebo
Arm Type
Experimental
Arm Description
Healthy participants will be randomized 3:1 to receive repeat doses either GSK3965193 (Dose Z) or placebo under fasted conditions. Part 2A may start while Part 1 is still ongoing. The starting dose in Part 2 will be at least 3-fold below the highest dose completed in Part 1.
Arm Title
Part 2B Cohort 6: GSK3965193
Arm Type
Experimental
Arm Description
Healthy Participants will be randomized 1:1 to receive single doses of GSK3965193 (Dose A) under fasted and fed conditions in treatment period 1. In period 2, the participants who received GSK3965193 (Dose A) under fasted conditions in treatment period 1 will receive the same dose under fed conditions, and vice versa. In the third period, all participants will receive a single dose of GSK3965193 (Dose B) different strength under fasted conditions. The dose level for the third period will be selected based on the results of the first two periods. There will be a minimum of 7 days washout between dosing in each treatment period.
Arm Title
Part 3 Cohort 7: GSK3965193 or placebo
Arm Type
Experimental
Arm Description
PLWCHB on stable nucleos(t)ide analog (NA) therapy will be randomized 3:1 to receive repeat dose of either GSK3965193 (Dose E) or placebo. This part will commence after completion of both Part 1 and Part 2.
Arm Title
Part 4 Cohort 8: GSK3965193 and bepirovirsen or placebo and bepirovirsen
Arm Type
Experimental
Arm Description
PLWCHB participants on stable NA therapy who have not participated in Part 3 of the study will be randomized 3:1 to receive repeat dose either GSK3965193 or placebo. In addition, all participants in this cohort will also receive bepirovirsen. This part will commence after completion of Part 3, contingent on the clinical safety and efficacy data from Part 3.
Intervention Type
Drug
Intervention Name(s)
GSK3965193
Intervention Description
GSK3965193 will be administered
Intervention Type
Drug
Intervention Name(s)
Placebo to match GSK3965193
Intervention Description
Placebo to match GSK3965193 will be administered
Intervention Type
Drug
Intervention Name(s)
Bepirovirsen
Intervention Description
Bepirovirsen will be administered
Primary Outcome Measure Information:
Title
Parts 1 and 2B: Number of participants with adverse events (AEs), serious adverse events (SAEs), and withdrawals due to AEs
Time Frame
Up to 14 days
Title
Part 2A: Number of participants with AEs, SAEs, and withdrawals due to AEs
Time Frame
Up to 42 Days
Title
Parts 1 and 2B: Number of participants with clinically significant changes in laboratory parameters
Time Frame
Up to 2 days
Title
Parts 1 and 2B: Number of participants with clinically significant changes in vital signs and cardiac parameters (electrocardiogram [ECG])
Time Frame
Up to 14 days
Title
Part 2A: Number of participants with clinically significant changes in laboratory parameters, vital signs, cardiac parameters (ECG)
Time Frame
Up to 21 days
Title
Part 2A: Number of participants with clinically significant nerve changes
Time Frame
Up to 6 weeks
Title
Part 1 and 2B: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-inf]) of GSK3965193 following single dose administration
Time Frame
Up to 4 days
Title
Part 2A: AUC(0-tau) of GSK3965193 following repeat dose administration
Time Frame
Up to 17 days
Title
Part 1 and 2B: maximum observed concentration (Cmax) of GSK3965193 following single dose administration
Time Frame
Up to 4 days
Title
Part 2A: Cmax of GSK3965193 following repeat dose administration
Time Frame
Up to 17 days
Title
Part 1 and 2B: Time to maximum observed plasma drug concentration (Tmax) of GSK3965193 following single dose administration
Time Frame
Up to 4 days
Title
Part 2A: Tmax of GSK3965193 following repeat dose administration
Time Frame
Up to 17 days
Title
Part 1 and 2B: Apparent terminal half-life (T1/2) of GSK3965193 following single dose administration
Time Frame
Up to 4 days
Title
Part 2A: T1/2 of GSK3965193 following repeat dose administration
Time Frame
Up to 17 days
Title
Part 3: Number of participants with AEs, SAEs, and withdrawals due to AEs
Time Frame
Up to 85 days
Title
Part 4: Number of participants with AEs, SAEs, and withdrawals due to AEs
Time Frame
Up to 36 weeks
Title
Part 3: Number of participants with clinically significant changes in laboratory parameters and vital signs
Time Frame
Up to 85 days
Title
Part 3: Number of participants with clinically significant changes in cardiac parameters (ECG)
Time Frame
Up to 36 days
Title
Part 4: Number of participants with clinically significant changes in laboratory parameters and vital signs
Time Frame
Up to 36 weeks
Title
Part 4: Number of participants with clinically significant changes in cardiac parameters (ECG)
Time Frame
Up to 13 weeks
Title
Part 3: Number of participants with clinically significant nerve changes
Time Frame
Up to 85 days
Title
Part 4: Number of participants with clinically significant nerve changes
Time Frame
Up to 13 weeks
Title
Part 3: Change from Baseline in HBsAg levels
Time Frame
Baseline and up to 6 weeks
Title
Part 4 : Number of participants achieving sustained virologic response
Time Frame
Up to 36 weeks
Title
Parts 1 and 2B: Number of participants with. adverse events (AEs), serious adverse events. (SAEs), and withdrawals due to AEs
Time Frame
Up to 14 days
Title
Parts 1 and 2B: Number of participants with. clinically significant changes in laboratory. parameters
Time Frame
Up to 2 days
Title
Parts 1 and 2B: Number of participants with. clinically significant changes in vital signs and. cardiac parameters (electrocardiogram [ECG])
Time Frame
Up to 14 days
Title
Part 2A: Number of participants with clinically. significant changes in laboratory parameters, vital signs, cardiac parameters (ECG)
Time Frame
Up to 21 days
Title
Part 2A: Number of participants with clinically. significant nerve changes
Time Frame
Up to 42 Days
Title
Part 2A: T1/2 of GSK3965193 following repeat. dose administration
Time Frame
Up to 17 days
Title
Part 3: Number of participants with clinically. significant changes in laboratory parameters and vital signs
Time Frame
Up to 85 days
Title
Part 3: Number of participants with clinically. significant changes in cardiac parameters (ECG)
Time Frame
Up to 36 days
Title
Part 4: Number of participants with clinically. significant changes in laboratory parameters and vital signs
Time Frame
Up to 36 weeks
Title
Part 4: Number of participants with clinically. significant changes in cardiac parameters (ECG)
Time Frame
Up to 13 weeks
Title
Part 3: Number of participants with clinically. significant nerve changes
Time Frame
Up to 85 days
Title
Part 4: Number of participants with clinically. significant nerve changes
Time Frame
Up to 13 weeks
Title
Part 3: Maximum reduction of serum HBsAg levels from Baseline
Time Frame
Baseline and up to 6 weeks
Title
Part 4: Number of participants achieving. sustained virologic response
Time Frame
Up to 36 weeks
Secondary Outcome Measure Information:
Title
Part 2B: AUC(0-inf) of GSK3965193 following single dose administration
Time Frame
Up to 5 days
Title
Part 2B: Cmax of GSK3965193 following single dose administration
Time Frame
Up to 5 days
Title
Part 3: AUC(0-tau) of GSK3965193 following repeat dose administration
Time Frame
Up to 29 days
Title
Part 3: Cmax of GSK3965193 following repeat dose administration
Time Frame
Up to 29 days
Title
Part 3: Tmax of GSK3965193 following repeat dose administration
Time Frame
Up to 29 days
Title
Part 3: T1/2 of GSK3965193 following repeat dose administration
Time Frame
Up to 29 days
Title
Part 3: Change from Baseline in HBsAg levels (greater than or equal to [>=] 0.5 times log international units per milliliters [IU/mL])
Time Frame
Baseline and up to 85 days
Title
Part 4: Number of participants with HBsAg loss
Time Frame
Up to 36 weeks
Title
Part 2B: AUC (0-inf) of GSK3965193 following. single dose administration
Time Frame
Up to 4 days
Title
Part 2B: Cmax of GSK3965193 following single. dose administration
Time Frame
Up to 4 days
Title
Part 3: AUC(0-tau) of GSK3965193 following. repeat dose administration
Time Frame
Up to 29 days
Title
Part 3: Tmax of GSK3965193 following repeat. dose administration
Time Frame
Up to 29 days
Title
Part 3: T1/2 of GSK3965193 following repeat. dose administration
Time Frame
Up to 29 days
Title
Part 3: Change from baseline in serum HBsAg levels from baseline. (greater than or equal to [≥] 0.5 times log. international units per milliliters [IU/mL])
Time Frame
Baseline and up to 85 days
Title
Number of participants with HBsAg loss
Time Frame
Up to 36 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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 non-childbearing potential only. b. Parts 3 and 4: woman of non-childbearing 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 in medical history, 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 8 weeks prior to the first dose of study drug 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 of screening, 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name or Official Title & Degree
EU GSK Clinical Trials Call Center
Phone
+44 (0) 20 89904466
Email
GSKClinicalSupportHD@gsk.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Cambridge
ZIP/Postal Code
CB2 2GG
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
EU GSK Clinical Trials Call Centre
Phone
+44 (0) 20 8990 4466
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
Disala Fernando

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD for this study will be made available via the Clinical Study Data Request site.
IPD Sharing Time Frame
IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
IPD Sharing Access Criteria
Access is provided after a research proposal is submitted and has received approval from the 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 can be granted, when justified, for up to another 12 months.
IPD Sharing URL
http://clinicalstudydatarequest.com

Learn more about this trial

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

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