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

Systemic Lupus Erythematosus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06188507
• Other study ID #: 221220
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: January 11, 2024
• Est. completion date: March 31, 2025

Study information

• Verified date: December 2023
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 44
• Est. completion date: March 31, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Drug:
• GSK4347859
GSK4347859 will be administered
• Placebo
Placebo will be administered

Locations

Country	Name	City	State
United Kingdom	GSK Investigational Site	Cambridge

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1 - Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)		Up to Day 15
Primary	Part 2 - Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)		Up to Day 30
Primary	Part 1 - Number of Participants with Clinically Significant Changes in Haematology		Up to Day 15
Primary	Part 2 - Number of Participants with Clinically Significant Changes in Haematology		Up to Day 30
Primary	Part 1 - Number of Participants with Clinically Significant Changes in Clinical Chemistry		Up to Day 15
Primary	Part 2 - Number of Participants with Clinically Significant Changes in Clinical Chemistry		Up to Day 30
Primary	Part 1 - Number of Participants with Clinically Significant Changes in Laboratory Values for Urinalysis		Up to Day 15
Primary	Part 2 - Number of Participants with Clinically Significant Changes in Urinalysis		Up to Day 30
Primary	Part 1 - Number of Participants with Clinically Significant Changes in Vital Signs		Up to Day 15
Primary	Part 2 - Number of Participants with Clinically Significant Changes in Vital Signs		Up to Day 30
Primary	Part 1 - Number of Participants with Clinically Significant Changes in 12 Lead Electrocardiogram Readings		Up to Day 15
Primary	Part 2 - Number of Participants with Clinically Significant Changes in 12 Lead Electrocardiogram Readings		Up to Day 30
Primary	Part 1 - Number of Participants with Clinically Significant Changes in 24 Hour Telemetry		Up to Day 2
Primary	Part 2 - Number of Participants with Clinically Significant Changes in 24 Hour Telemetry		Up to Day 15
Secondary	Part 1 - Maximum observed plasma concentration (Cmax) of GSK3996401 following administration of GSK4347859		Up to Day 3
Secondary	Part 1 - Time to maximum observed plasma concentration (Tmax) of GSK3996401 following administration of GSK4347859		Up to Day 3
Secondary	Part 1 - Apparent terminal half-life (t½) of GSK3996401 following administration of GSK4347859		Up to Day 3
Secondary	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
Secondary	Part 1 - Area under the concentration-time curve from time zero to infinity [AUC(0-8)] of GSK3996401 following administration of GSK4347859		Up to Day 3
Secondary	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
Secondary	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
Secondary	Part 1 - Observed trough concentrations (Ctrough) of GSK3996401 following administration of GSK4347859		Up to Day 3
Secondary	Part 2 - Cmax of GSK3996401 following administration of single and repeat doses of GSK4347859		Up to Day 15
Secondary	Part 2 - Tmax of GSK3996401 following administration of single and repeat doses of GSK4347859		Up to Day 15
Secondary	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
Secondary	Part 2 - Observed trough concentrations (Ctrough) of GSK3996401 following administration of GSK4347859		Up to Day 15
Secondary	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