DIONE - Efficacy and Safety of TD-1473 in Crohn’s Disease
Research type
Research Study
Full title
A Phase 2 Multi-Center, Randomized, Double-Blind, Placebo˗Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Induction Therapy with 2 Doses of TD-1473 in Subjects with Moderately-to-Severely Active Crohn’s Disease
IRAS ID
249575
Contact name
John Paul Seenan
Contact email
Sponsor organisation
Theravance Biopharma Ireland Limited
Eudract number
2018-001272-37
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
US IND:, 139,354
Duration of Study in the UK
1 years, 7 months, 3 days
Research summary
Research Summary
Crohn’s Disease (CD) is a chronic gastrointestinal disease which has emerged in the past decade as a worldwide public health challenge. CD and Ulcerative colitis (UC), the two subtypes of inflammatory bowel disease (IBD), affect over 1.5 million and 2 million people in North America and Europe respectively. CD can be a debilitating condition for patients with chronic symptoms including abdominal pain, diarrhoea and weight loss. Current maintenance therapies may be limited by side effects (including infection and risk of cancer), often require regular injections/infusions and can lose effect over time. There is therefore an unmet clinical need for a treatment with better efficacy, safety profile, ease of administration and durable response for patients.
The purpose of this clinical study is to evaluate TD-1473, which is an orally administered study medication designed to act against the chronic inflammation in the bowel while minimising exposure to the rest of the body.
The study will include patients with moderately-to-severely active CD and is designed to include 3 phases; screening, induction and active treatment extension. Approximately 160 male and female participants aged over 18 will be allocated by randomisation (like rolling a dice) to receive active treatment, with 80 mg or 200 mg of TD-1473, or placebo in ratio 3:3:2, in a 12-week long induction period. The participants will then enter a 24 week long active treatment period, in which all participants will receive 80 mg or 200 mg of TD-1473. During the study, participants will meet with the study doctor 12 times over an 11-month period.
Throughout the study, participants will be required to complete certain procedures, such as blood tests, questionnaires and X-rays. Participants will be recruited at study sites in the UK, and globally.
Summary of Research
159 participants were recruited to be in the study and, of these 130 (81.8%) completed the week 12 visit. Following analysis for the primary study endpoint, a small dose-response trend was observed as early as Week 4, but no statistically significant difference was observed between the TD-1473 and the placebo treatment groups at Week 12. For the secondary endpoints, no difference was observed between treatment groups in terms of response or remission. For the exploratory endpoints, no meaningful improvements were observed. Based on the lack of meaningful improvements observed at Week 12, the study was ended early by the Sponsor upon recommendation of the independent data monitoring committee. The study was not ended early due to safety reasons. Overall, TD-1473 doses of 80 mg and 200 mg were generally safe and well tolerated by the participants in this study.
REC name
North West - Haydock Research Ethics Committee
REC reference
18/NW/0713
Date of REC Opinion
15 Nov 2018
REC opinion
Further Information Favourable Opinion