Evaluating the safety of a new drug in healthy participants

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 study is testing a new drug called GSK4347859 in healthy people to see if it's safe and how their bodies react to it before it’s used in patients with lupus.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 65 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: GlaxoSmithKline (Industry-sponsored)
• Locations: 2 sites (Cambridge and 1 other locations)
• Trial ID: NCT06188507 on ClinicalTrials.gov

What this trial studies

This study is designed to assess the safety and tolerability of GSK4347859, a new medication, in healthy individuals. It involves administering single and multiple ascending doses of GSK4347859 to evaluate how the body responds to the drug and to measure the concentration of its active form, GSK3996401, in the bloodstream. The study is divided into two parts: the first part focuses on single doses, while the second part examines the effects of repeated dosing over 14 days. The goal is to gather essential safety data before further testing in patients with systemic lupus erythematosus.

Who should consider this trial

Good fit: Ideal candidates for this study are healthy adults who meet specific health criteria and are capable of providing informed consent.

Not a fit: Patients with existing health conditions or those who do not meet the eligibility criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to the development of a new treatment option for patients with systemic lupus erythematosus.

How similar studies have performed: While this is a first-time-in-human study, similar studies have shown success in evaluating new treatments for various conditions.

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.
* 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.

Where this trial is running

Cambridge and 1 other locations

• GSK Investigational Site — Cambridge, United Kingdom (Recruiting)
• GSK Investigational Site — Nottingham, United Kingdom (Recruiting)

Study contacts

• Study coordinator: US GSK Clinical Trials Call Center

Conditions Systemic Lupus Erythematosus; Lupus; GSK4347859; GSK3996401; Safety; First time in human; Pharmacokinetics; Healthy Participants