A First Time in Human Study to Evaluate the Safety and Tolerability of GSK3996401 Following Dosing With GSK4347859 in Healthy Participants

NCT06188507 | Suspended Phase 1 DMC

• 1 other identifier: 221220
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 2

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.

Conditions

Systemic Lupus Erythematosus

Keywords

Lupus; GSK4347859; GSK3996401; Safety; First time in human (FTiH); Pharmacokinetics; Healthy Participants

Outcome Measures

Primary Outcomes (14)

• Part 1 - Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up to Day 15

• Part 2 - Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up to Day 30

• Part 1 - Number of Participants with Clinically Significant Changes in Haematology

  Up to Day 15

• Part 2 - Number of Participants with Clinically Significant Changes in Haematology

  Up to Day 30

• Part 1 - Number of Participants with Clinically Significant Changes in Clinical Chemistry

  Up to Day 15

• Part 2 - Number of Participants with Clinically Significant Changes in Clinical Chemistry

  Up to Day 30

• Part 1 - Number of Participants with Clinically Significant Changes in Laboratory Values for Urinalysis

  Up to Day 15

• Part 2 - Number of Participants with Clinically Significant Changes in Urinalysis

  Up to Day 30

• Part 1 - Number of Participants with Clinically Significant Changes in Vital Signs

  Up to Day 15

• Part 2 - Number of Participants with Clinically Significant Changes in Vital Signs

  Up to Day 30

• Part 1 - Number of Participants with Clinically Significant Changes in 12 Lead Electrocardiogram Readings

  Up to Day 15

• Part 2 - Number of Participants with Clinically Significant Changes in 12 Lead Electrocardiogram Readings

  Up to Day 30

• Part 1 - Number of Participants with Clinically Significant Changes in 24 Hour Telemetry

  Up to Day 2

• Part 2 - Number of Participants with Clinically Significant Changes in 24 Hour Telemetry

  Up to Day 15

Secondary Outcomes (13)

• Part 1 - Maximum observed plasma concentration (Cmax) of GSK3996401 following administration of GSK4347859

  Up to Day 3

• 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

Study Arms (5)

Part 1: Cohort 1-GSK4347859 or Placebo

EXPERIMENTAL

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.

Drug: GSK4347859; Drug: Placebo

Part 1: Cohort 2-GSK4347859 or Placebo

EXPERIMENTAL

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.

Drug: GSK4347859; Drug: Placebo

Part 2: Cohort 3-GSK4347859 or Placebo

EXPERIMENTAL

Participants in Part 2 Cohort 3 will receive 14 days of repeat doses of GSK4347859 dose level A or placebo.

Drug: GSK4347859; Drug: Placebo

Part 2: Cohort 4-GSK4347859 or Placebo

EXPERIMENTAL

Participants in Part 2 Cohort 4 will receive 14 days of repeat doses of GSK4347859 dose level B or placebo.

Drug: GSK4347859; Drug: Placebo

Part 2: Cohort 5-GSK4347859 or Placebo

EXPERIMENTAL

Participants in Part 2 Cohort 5 will receive 14 days of repeat doses of GSK4347859 dose level C or placebo.

Drug: GSK4347859; Drug: Placebo

Interventions

GSK4347859 DRUG

GSK4347859 will be administered

Part 1: Cohort 1-GSK4347859 or Placebo; Part 1: Cohort 2-GSK4347859 or Placebo; Part 2: Cohort 3-GSK4347859 or Placebo; Part 2: Cohort 4-GSK4347859 or Placebo; Part 2: Cohort 5-GSK4347859 or Placebo

Placebo DRUG

Placebo will be administered

Part 1: Cohort 1-GSK4347859 or Placebo; Part 1: Cohort 2-GSK4347859 or Placebo; Part 2: Cohort 3-GSK4347859 or Placebo; Part 2: Cohort 4-GSK4347859 or Placebo; Part 2: Cohort 5-GSK4347859 or Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Past or intended use of over-the-counter or prescription medication including herbal medications within 7 days prior to dosing
• The participant has participated in a clinical trial and has received an investigational product within 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product and dosing.
• Current enrolment or past participation in this clinical study
• Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention
• Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Cambridge, CB2 2GG, United Kingdom

Location

GSK Investigational Site

Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Click here to enter text.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2023
• First Posted: January 3, 2024
• Study Start: January 12, 2024
• Primary Completion (Estimated): July 14, 2026
• Study Completion (Estimated): July 14, 2026
• Last Updated: October 3, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 months.

Locations

GB (2)