A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK3996401 Following Single and Multiple Ascending Doses of GSK4347859 in Healthy Participants
Overview
- Phase
- Phase 1
- Intervention
- GSK4347859
- Conditions
- Systemic Lupus Erythematosus
- Sponsor
- GlaxoSmithKline
- Enrollment
- 65
- Locations
- 1
- Primary Endpoint
- Part 1 - Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
- Status
- Suspended
- Last Updated
- 7 months ago
Overview
Brief Summary
This is a first time in human (FTiH) study which means that this is the first time that GSK4347859 is given to humans. The study is designed to investigate the safety, tolerability, and concentration of GSK3996401 (the activated form of GSK4347859) in the blood following single ascending doses (Part 1) and multiple ascending doses (Part 2) of GSK4347859 in healthy participants. Part 1 consists of 2 planned cohorts with up to 4 treatment periods in each and is expected to have up to 8 dose levels. Part 2 will investigate 14 days of repeat dosing in 3 cohorts with 3 dose levels.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants who are overtly healthy.
- •Participant has a confirmed positive vaccination status for severe acute respiratory syndrome-related Coronavirus (2 SARS-CoV-2) and, if study dosing is during Flu season, influenza vaccines administered at least 30 days prior to dosing in the study.
- •Fitzpatrick skin type I, II or III (Part 2 only).
- •Body weight greater than or equal to (≥) 50 kilogram (kg) and body mass index (BMI) within the range 18 -32 kilogram per meter square (kg/m\^2) (inclusive).
- •Male and female of non-childbearing potential.
- •Capable of giving signed informed consent.
Exclusion Criteria
- •History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric, or neurological disorders. - Abnormal blood pressure
- •A clinically significant ECG abnormality at screening.
- •Evidence of active or latent tuberculosis (TB).
- •Symptomatic herpes zoster within 3 months prior to screening
- •Alanine transaminase (ALT) \>1 times upper limit of normal (ULN).
- •Total bilirubin \>1.5x ULN \[isolated total bilirubin \>1.5x ULN is acceptable if total bilirubin is fractionated and direct bilirubin \<35- percentage (%)\].
- •History of malignancy.
- •Participants with known Corona virus disease-2019 (COVID-19) positive contacts as per local/site Guidelines
- •Prior moderate/severe COVID-19 infection requiring oxygen supplementation or admission to hospital.
- •Live vaccine(s) within 1 month prior to screening or plan to receive such vaccines during the study.
Arms & Interventions
Part 1: Cohort 1-GSK4347859 or Placebo
Participants in Part 1 Cohort 1 will receive a single dose level of GSK4347859 dose level 1 or placebo in treatment period 1, followed by GSK4347859 dose levels 2 and 3 or placebo in 3- period dose escalation design. Additionally, there will be an optional 4th treatment period with dose level 4. Followed by a wash out period of at least 7 days between each dose.
Intervention: GSK4347859
Part 1: Cohort 1-GSK4347859 or Placebo
Participants in Part 1 Cohort 1 will receive a single dose level of GSK4347859 dose level 1 or placebo in treatment period 1, followed by GSK4347859 dose levels 2 and 3 or placebo in 3- period dose escalation design. Additionally, there will be an optional 4th treatment period with dose level 4. Followed by a wash out period of at least 7 days between each dose.
Intervention: Placebo
Part 1: Cohort 2-GSK4347859 or Placebo
Participants in Part 1 Cohort 2 will receive a single dose level of GSK4347859 dose level 5 or placebo in treatment period 1, followed by GSK4347859 dose levels 6 and 7 or placebo in 3- period dose escalation design. Additionally, there will be an optional 4th treatment period with dose level 8. Followed by a wash out period of at least 7 days between each dose.
Intervention: GSK4347859
Part 1: Cohort 2-GSK4347859 or Placebo
Participants in Part 1 Cohort 2 will receive a single dose level of GSK4347859 dose level 5 or placebo in treatment period 1, followed by GSK4347859 dose levels 6 and 7 or placebo in 3- period dose escalation design. Additionally, there will be an optional 4th treatment period with dose level 8. Followed by a wash out period of at least 7 days between each dose.
Intervention: Placebo
Part 2: Cohort 3-GSK4347859 or Placebo
Participants in Part 2 Cohort 3 will receive 14 days of repeat doses of GSK4347859 dose level A or placebo.
Intervention: GSK4347859
Part 2: Cohort 3-GSK4347859 or Placebo
Participants in Part 2 Cohort 3 will receive 14 days of repeat doses of GSK4347859 dose level A or placebo.
Intervention: Placebo
Part 2: Cohort 4-GSK4347859 or Placebo
Participants in Part 2 Cohort 4 will receive 14 days of repeat doses of GSK4347859 dose level B or placebo.
Intervention: GSK4347859
Part 2: Cohort 4-GSK4347859 or Placebo
Participants in Part 2 Cohort 4 will receive 14 days of repeat doses of GSK4347859 dose level B or placebo.
Intervention: Placebo
Part 2: Cohort 5-GSK4347859 or Placebo
Participants in Part 2 Cohort 5 will receive 14 days of repeat doses of GSK4347859 dose level C or placebo.
Intervention: GSK4347859
Part 2: Cohort 5-GSK4347859 or Placebo
Participants in Part 2 Cohort 5 will receive 14 days of repeat doses of GSK4347859 dose level C or placebo.
Intervention: Placebo
Outcomes
Primary Outcomes
Part 1 - Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Up to Day 15
Part 2 - Number of Participants with Clinically Significant Changes in 12 Lead Electrocardiogram Readings
Time Frame: Up to Day 30
Part 1 - Number of Participants with Clinically Significant Changes in 24 Hour Telemetry
Time Frame: Up to Day 2
Part 2 - Number of Participants with Clinically Significant Changes in 24 Hour Telemetry
Time Frame: Up to Day 15
Part 2 - Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Up to Day 30
Part 1 - Number of Participants with Clinically Significant Changes in Haematology
Time Frame: Up to Day 15
Part 2 - Number of Participants with Clinically Significant Changes in Haematology
Time Frame: Up to Day 30
Part 2 - Number of Participants with Clinically Significant Changes in Clinical Chemistry
Time Frame: Up to Day 30
Part 2 - Number of Participants with Clinically Significant Changes in Vital Signs
Time Frame: Up to Day 30
Part 1 - Number of Participants with Clinically Significant Changes in Clinical Chemistry
Time Frame: Up to Day 15
Part 1 - Number of Participants with Clinically Significant Changes in Laboratory Values for Urinalysis
Time Frame: Up to Day 15
Part 2 - Number of Participants with Clinically Significant Changes in Urinalysis
Time Frame: Up to Day 30
Part 1 - Number of Participants with Clinically Significant Changes in Vital Signs
Time Frame: Up to Day 15
Part 1 - Number of Participants with Clinically Significant Changes in 12 Lead Electrocardiogram Readings
Time Frame: Up to Day 15
Secondary Outcomes
- Part 1 - Time to maximum observed plasma concentration (Tmax) of GSK3996401 following administration of GSK4347859(Up to Day 3)
- Part 1 - Apparent terminal half-life (t½) of GSK3996401 following administration of GSK4347859(Up to Day 3)
- Part 1 - Area under the concentration-time curve from zero to last quantifiable concentration [AUC(0-t)] of GSK3996401 following administration of GSK4347859(Up to Day 3)
- Part 1 - Area under the concentration-time curve from time zero to infinity [AUC(0-∞)] of GSK3996401 following administration of GSK4347859(Up to Day 3)
- Part 1 - Area under the concentration-time curve from time zero to 24 hours after dosing [AUC(0-24)] of GSK3996401 following administration of GSK4347859(Up to Day 3)
- Part 1 - Maximum observed plasma concentration (Cmax) of GSK3996401 following administration of GSK4347859(Up to Day 3)
- Part 1 - Area under the concentration-time curve over each dosing interval [AUC(0-tau)] of GSK3996401 following administration of GSK4347859(Up to Day 3)
- Part 1 - Observed trough concentrations (Ctrough) of GSK3996401 following administration of GSK4347859(Up to Day 3)
- Part 2 - Observed trough concentrations (Ctrough) of GSK3996401 following administration of GSK4347859(Up to Day 15)
- Part 2 - Cmax of GSK3996401 following administration of single and repeat doses of GSK4347859(Up to Day 15)
- Part 2 - Tmax of GSK3996401 following administration of single and repeat doses of GSK4347859(Up to Day 15)
- Part 2 - Area under the concentration-time curve from time zero to 24 hours after dosing [AUC(0-24)] of GSK3996401 following administration single and repeat doses of GSK4347859(Up to Day 15)
- Part 2 - Area under the concentration-time curve over each dosing interval [AUC(0-tau)] of GSK3996401 following administration of GSK4347859(Up to Day 15)