ENTO in Chronic Graft Versus Host Disease
Research type
Research Study
Full title
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Tolerability of Entospletinib, a Selective SYK Inhibitor, in Combination with Systemic Corticosteroids as First-Line Therapy in Subjects with Chronic Graft Versus Host Disease (cGVHD)
IRAS ID
198004
Contact name
Fiona Dignan
Contact email
Sponsor organisation
Gilead Sciences, Inc.
Eudract number
2015-004572-30
Duration of Study in the UK
3 years, 9 months, 28 days
Research summary
The study is a randomised, double-blind, placebo-controlled, multicentre study to evaluate the efficacy and safety of Entospletinib (ENTO) (Treatment Arm 1) vs. placebo (Treatment Arm 2) in combination with systemic corticosteroids for participants with cGVHD.
The purpose of this study is to assess the efficacy of a new experimental medication, ENTO, in participants with cGVHD, in addition to systemic corticosteroids as part of first-line therapy for cGVHD. The study aims to enrol approximately 100 adult male and female participants with cGVHD at approximately 30 sites in North America, Europe, Asia and Australia. The participants will receive study medication (ENTO) or placebo for 48 weeks, before having the option to receive open-label ENTO for an additional 96 weeks.
Chronic Graft Versus Host Disease (cGVHD) is a disease observed in recipients of allogeneic haematopoietic stem cells, where the new immune system begins to attack multiple organ systems including eyes, skin, mucosa, lungs, gut, and liver. Chronic GVHD occurs in 35-70% of patients receiving allogeneic transplants. Initial therapy for cGVHD consists of high dose systemic corticosteroids, however 50 to 60% of patients fail to have a complete response to this line of therapy.
No agents are currently approved for cGVHD. The majority of responses to second-line therapies are not durable, and cGVHD is associated with a 5-year mortality of 30-50%. Current immunosuppressive treatments also increase the rate of life-threatening infections and cancer relapse.
The current biological and clinical evidence suggests that an imbalance of B cells (a type of white blood cell involved in the immune response) is involved in cGVHD. Research suggests that the inhibition of SYK (an enzyme called Spleen tyrosine kinase) may help to restore the balance of B cells in participants with cGVHD. ENTO is a highly selective inhibitor of SYK.REC name
South West - Central Bristol Research Ethics Committee
REC reference
16/SW/0044
Date of REC Opinion
10 Mar 2016
REC opinion
Favourable Opinion