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

Sponsor
GlaxoSmithKline
Study ID
NCT05330455
Phase
PHASE1/PHASE2
Status
Terminated

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 65 Years
Healthy Volunteers
Accepted

Interventions

  • GSK3965193 — DRUG
    GSK3965193 was administered
  • Placebo to match GSK3965193 — DRUG
    Placebo to match GSK3965193 was administered
  • Bepirovirsen — DRUG
    Bepirovirsen was administered

Study Details

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.

Key Dates

Start date
Apr 14, 2022
Status verified
May 2026
Primary completion
May 19, 2025
Completion
Apr 8, 2026

Study Design

Enrollment
74 participants (actual)
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT

Arms

  • Experimental: Part 1: Cohort 1 - Placebo/GSK3965193 Dose 2/Dose 3/Dose 4
    Healthy participants received a single dose of placebo oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 2 oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 3 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 4 oral solution on Day 1 in Treatment Period 4. Dose 4 of GSK3965193 was higher than Dose 3 and Dose 3 was higher than Dose 2.
  • Experimental: Part 1: Cohort 1 - GSK3965193 Dose 1/Placebo/Dose 3/Dose 4
    Healthy participants received a single dose of GSK3965193 Dose 1 oral solution on Day 1 in Treatment Period 1; followed by a single dose of placebo oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 3 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 4 oral solution on Day 1 in Treatment Period 4. Dose 4 of GSK3965193 was higher than Dose 3 and Dose 3 was higher than Dose 1.
  • Experimental: Part 1: Cohort 1 - GSK3965193 Dose 1/Dose 2/Placebo/Dose 4
    Healthy participants received a single dose of GSK3965193 Dose 1 oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 2 oral solution on Day 1 in Treatment Period 2; followed by a single dose of placebo oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 4 oral solution on Day 1 in Treatment Period 4. Dose 4 of GSK3965193 was higher than Dose 2 and Dose 2 was higher than Dose 1.
  • Experimental: Part 1: Cohort 1 - GSK3965193 Dose 1/Dose 2/Dose 3/Placebo
    Healthy participants received a single dose of GSK3965193 Dose 1 oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 2 oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 3 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of placebo oral solution on Day 1 in Treatment Period 4. Dose 3 of GSK3965193 was higher than Dose 2 and Dose 2 was higher than Dose 1.
  • Experimental: Part 1: Cohort 2 - Placebo/GSK3965193 Dose 6/Dose 7/Dose 8
    Healthy participants received a single dose of placebo oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 6 oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 7 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 8 oral solution on Day 1 in Treatment Period 4. Dose 8 of GSK3965193 was higher than Dose 7 and Dose 7 was higher than Dose 6.
  • Experimental: Part 1: Cohort 2 - GSK3965193 Dose 5/Placebo/Dose 7/Dose 8
    Healthy participants received a single dose of GSK3965193 Dose 5 oral solution on Day 1 in Treatment Period 1; followed by a single dose of placebo oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 7 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 8 oral solution on Day 1 in Treatment Period 4. Dose 8 of GSK3965193 was higher than Dose 7 and Dose 7 was higher than Dose 5.
  • Experimental: Part 1: Cohort 2 - GSK3965193 Dose 5/Dose 6/Placebo/Dose 8
    Healthy participants received a single dose of GSK3965193 Dose 5 oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 6 oral solution on Day 1 in Treatment Period 2; followed by a single dose of placebo oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 8 oral solution on Day 1 in Treatment Period 4. Dose 8 of GSK3965193 was higher than Dose 6 and Dose 6 was higher than Dose 5.
  • Experimental: Part 1: Cohort 2 - GSK3965193 Dose 5/Dose 6/Dose 7/Placebo
    Healthy participants received a single dose of GSK3965193 Dose 5 oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 6 oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 7 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of placebo oral solution on Day 1 in Treatment Period 4. Dose 7 of GSK3965193 was higher than Dose 6 and Dose 6 was higher than Dose 5.
  • Placebo Comparator: Part 2A: Placebo
    Healthy participants received repeat doses of placebo oral solution twice daily (BID) for 14 days.
  • Experimental: Part 2A: Cohort 5 - GSK3965193 Dose 9 BID
    Healthy participants received repeat doses of GSK3965193 Dose 9 oral solution BID for 14 days. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
  • Experimental: Part 2A: Cohort 3 - GSK3965193 Dose 5 BID
    Healthy participants received repeat doses of GSK3965193 Dose 5 oral solution BID for 14 days. Dose 5 of GSK3965193 was higher than Dose 9 but lower than Dose 10.
  • Experimental: Part 2A: Cohort 4 - GSK3965193 Dose 6 BID
    Healthy participants received repeat doses of GSK3965193 Dose 6 oral solution BID for 14 days. Dose 6 of GSK3965193 was higher than Dose 10 but lower than Dose 7.
  • Experimental: Part 2B: Cohort 6 - GSK3965193 Dose 10 Fasted/Fed
    Healthy participants received GSK3965193 Dose 10 oral tablets under fasted condition in Treatment Period 1, followed by GSK3965193 Dose 10 oral tablets under fed condition in Treatment Period 2. Dose 10 of GSK3965193 was higher than Dose 5 but lower than Dose 6.
  • Experimental: Part 2B: Cohort 6 - GSK3965193 Dose 10 Fed/Fasted
    Healthy participants received GSK3965193 Dose 10 oral tablets under fed condition in Treatment Period 1, followed by GSK3965193 Dose 10 oral tablets under fasted condition in Treatment Period 2. Dose 10 of GSK3965193 was higher than Dose 5 but lower than Dose 6.
  • Placebo Comparator: Part 3: Cohort 7 - Placebo
    Participants living with chronic hepatitis B infection (PLWCHB) on stable nucleos(t)ide analog (NA) therapy received repeat doses of placebo oral tablets for 28 days. Participants who completed placebo monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen subcutaneous (SC) injection from Day 43.
  • Experimental: Part 3: Cohort 7 - GSK3965193 Dose 9
    PLWCHB on stable NA therapy received repeat doses of GSK3965193 Dose 9 oral tablets for 28 days. Participants who completed GSK3965193 monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen SC injection from Day 43. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
  • Experimental: Part 4: Cohort 8 - Placebo + Bepirovirsen
    PLWCHB on stable NA therapy were planned to receive placebo oral tablets plus bepirovirsen SC injection for 28 days. All participants were further planned to continue receiving bepirovirsen SC injection after 28 days.
  • Experimental: Part 4: Cohort 8 - GSK3965193 + Bepirovirsen
    PLWCHB on stable NA therapy were planned to receive GSK3965193 oral tablets plus bepirovirsen SC injection for 28 days. All participants were further planned to continue receiving bepirovirsen SC injection after 28 days.

Primary Outcome Measure

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 ]

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