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

September 30, 2025 updated by: GlaxoSmithKline

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Suspended

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
65

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United Kingdom
      • Cambridge, United Kingdom, CB2 2GG
        • GSK Investigational Site
      • Nottingham, United Kingdom, NG11 6JS
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

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.
  • 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
  • Positive hepatitis C Ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study
  • Positive pre-study drug/alcohol screen
  • Regular use of known drugs of abuse, including tetrahydrocannabinol.
  • Positive Human immunodeficiency virus (HIV) antibody test
  • Positive smoke breathalyzer levels indicative of smoking history at screening and each in-house admission to the clinical research unit or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
  • Estimated glomerular filtration rate (eGFR) of less than (<) 90 (millilitre/minute) mL/min/1.73 m2 and / or Urine Albumin Creatinine (UACR) of >30 milligram per gram (mg/g) at screening
  • A positive confirmation of SARS-CoV-2 infection or signs and symptoms suggestive of SARS-CoV-2 at screening or pre-dose
  • The participant has a phobia to needles
  • An average weekly alcohol intake of > 14 units.

For Part 2:

  • History of benign skin conditions including but not limited to photosensitivity, atopic dermatitis, chronic eczema, psoriasis, urticaria, vitiligo, post-inflammatory hyperpigmentation, or keloid or hypertrophic scaring that in the opinion of the Investigator would impact study participation.
  • History or presence of excessive bleeding or coagulation disorders.
  • History of adverse reaction to local anesthetic.
  • The presence of widespread acne, freckles, naevi, tattoos, birthmarks, piercings, scarring or other skin variations within the proposed Ultraviolet B (UVB) exposure challenge area
  • Direct UV exposure to the areas of the body to be studied within 2 weeks.
  • Unable to refrain from exposure to extended and direct sunlight or use of artificial tanning devices, self-tanning products, sun blocking products or other topical products (including moisturizers and makeup) on the areas of the body to be studied.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: Placebo
Placebo will be administered
Drug: GSK4347859
GSK4347859 will be administered
Experimental: 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.
Drug: Placebo
Placebo will be administered
Drug: GSK4347859
GSK4347859 will be administered
Experimental: 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.
Drug: Placebo
Placebo will be administered
Drug: GSK4347859
GSK4347859 will be administered
Experimental: 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.
Drug: Placebo
Placebo will be administered
Drug: GSK4347859
GSK4347859 will be administered
Experimental: 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.
Drug: Placebo
Placebo will be administered
Drug: GSK4347859
GSK4347859 will be administered

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Part 1 - Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Up to Day 15
Up to Day 15
Part 2 - Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Up to Day 30
Up to Day 30
Part 1 - Number of Participants with Clinically Significant Changes in Haematology
Time Frame: Up to Day 15
Up to Day 15
Part 2 - Number of Participants with Clinically Significant Changes in Haematology
Time Frame: Up to Day 30
Up to Day 30
Part 1 - Number of Participants with Clinically Significant Changes in Clinical Chemistry
Time Frame: Up to Day 15
Up to Day 15
Part 2 - Number of Participants with Clinically Significant Changes in Clinical Chemistry
Time Frame: Up to Day 30
Up to Day 30
Part 1 - Number of Participants with Clinically Significant Changes in Laboratory Values for Urinalysis
Time Frame: Up to Day 15
Up to Day 15
Part 2 - Number of Participants with Clinically Significant Changes in Urinalysis
Time Frame: Up to Day 30
Up to Day 30
Part 1 - Number of Participants with Clinically Significant Changes in Vital Signs
Time Frame: Up to Day 15
Up to Day 15
Part 2 - Number of Participants with Clinically Significant Changes in Vital Signs
Time Frame: Up to Day 30
Up to Day 30
Part 1 - Number of Participants with Clinically Significant Changes in 12 Lead Electrocardiogram Readings
Time Frame: Up to Day 15
Up to Day 15
Part 2 - Number of Participants with Clinically Significant Changes in 12 Lead Electrocardiogram Readings
Time Frame: Up to Day 30
Up to Day 30
Part 1 - Number of Participants with Clinically Significant Changes in 24 Hour Telemetry
Time Frame: Up to Day 2
Up to Day 2
Part 2 - Number of Participants with Clinically Significant Changes in 24 Hour Telemetry
Time Frame: Up to Day 15
Up to Day 15

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Part 1 - Maximum observed plasma concentration (Cmax) of GSK3996401 following administration of GSK4347859
Time Frame: Up to Day 3
Up to Day 3
Part 1 - Time to maximum observed plasma concentration (Tmax) of GSK3996401 following administration of GSK4347859
Time Frame: Up to Day 3
Up to Day 3
Part 1 - Apparent terminal half-life (t½) of GSK3996401 following administration of GSK4347859
Time Frame: Up to Day 3
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
Time Frame: Up to Day 3
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
Time Frame: Up to Day 3
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
Time Frame: Up to Day 3
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
Time Frame: Up to Day 3
Up to Day 3
Part 1 - Observed trough concentrations (Ctrough) of GSK3996401 following administration of GSK4347859
Time Frame: Up to Day 3
Up to Day 3
Part 2 - Cmax of GSK3996401 following administration of single and repeat doses of GSK4347859
Time Frame: Up to Day 15
Up to Day 15
Part 2 - Tmax of GSK3996401 following administration of single and repeat doses of GSK4347859
Time Frame: Up to Day 15
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
Time Frame: Up to Day 15
Up to Day 15
Part 2 - Observed trough concentrations (Ctrough) of GSK3996401 following administration of GSK4347859
Time Frame: Up to Day 15
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
Time Frame: Up to Day 15
Up to Day 15

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
GlaxoSmithKline

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 12, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 14, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 14, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 19, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 19, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 3, 2024

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 3, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 30, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 221220

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

IPD Sharing 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.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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