GSK4347859 vs PBO, Ph1, HV, SD&RD DE, FTIH, Safety, PK/PD
Research type
Research Study
Full 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.
IRAS ID
1008764
Contact name
Farazana Habib-Ullah
Contact email
Sponsor organisation
GlaxoSmithKline Research & Development Limited
Research summary
Lupus is a lifelong autoimmune disease in which the body’s immune system mistakenly attacks healthy tissue, causing inflammation and damage to many parts of the body.
GSK is developing a drug GSK4347859 for the treatment of lupus. Current therapies help reduce symptoms but some patients don’t respond well to these drugs and their disease progresses leading to irreversible organ damage.
It is expected that GSK4347859 will work by blocking cGAS, a chemical occurring naturally in the body which activates the immune system causing widespread inflammation and damage to healthy tissue in some patients. Research suggests that blocking cGAS may reduce inflammation in lupus patients which will improve their symptoms preventing further damage.
GSK4347859 is a “pro drug” which means it’s an inactive medication. Once it enters the body, the body turns it into an active form (which is referred to as GSK3996401).
This is the first time the study drug is being tested in people. It has only been tested in animals and in the laboratory. It will test:
1. If the study drug is well tolerated and has any side effects
2. How the body handles the study drug and how long it takes to be removed from the body?
3. How does the study drug work in your body?
4. Does your genetic makeup affect how the drug works in your body?
The study will include 49 healthy men and women of non-childbearing potential (18-55 years) in two parts. Part 1 will last for up to 19 weeks and 16 healthy people will receive a single dose of GSK4347859/placebo in a capsule. The dose level will be escalated and that single dose may be divided to be up to 4 times over one day. Part 2 will last for 13 weeks and 33 healthy people will receive repeat ascending doses of GSK4347859/placebo in capsules. There will be a skin immune challenge involving skin biopsies before and after UVB light exposure. Study participants will not benefit directly but may help GSK to develop a new drug for an unmet need in lupus.REC name
East of England - Cambridge East Research Ethics Committee
REC reference
23/EE/0259
Date of REC Opinion
12 Dec 2023
REC opinion
Further Information Favourable Opinion