Primary: Safety and tolerability.Secondary: Clinical and endoscopic remission, symptomatic clinical remission, clinical response, mucosal healing, health related QoL, CRP, faecal calprotectin, pharmacokinetics.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Adverse events.
Secondary outcome
Mayo-score, rectal bleeding, UCEIS (ulcerative colitis endoscopic index of
severity), IBDQ, CRP, faecal calprotectin, PK parameters.
Background summary
Ulcerative colitis is the most common inflammatory bowel disease worldwide. It
is characterised by bloody diarrhoea and there is often a disease pattern of
gradual onset, spontaneous remission and subsequent relapses. Symptoms of
frequent urgent diarrhoea, fatigue and abdominal pain significantly reduce
patient*s quality of life and productivity and current medical therapies only
moderately affect disease symptoms while exposing patients to substantial side
effects. Janus kinases (JAKs) are intracellular, non-receptor tyrosine
kinases. The JAK family in mammals consists of four members: JAK1, JAK2, JAK3
and TYK2. Stimulation of cells via cytokine and growth factor receptors
results in the activation of JAKs, and subsequent phosphorylation and
activation of the STAT (signal transduction and transcription) family of
transcription factors. Activated STATs are dimerised and translocated to the
nucleus, where they regulate transcription of STAT-dependent inflammatory genes.
GSK2586184 is an orally active, competitive, potent, selective JAK1 inhibitor.
Concentration-dependent JAK1 inhibition by GSK2586184 has been shown in an ex
vivo whole blood assay in clinical studies.
JAK*s are activated in response to some of the key cytokines implicated in
ulcerative colitis, for example type 1 interferons (IFN), IFN-* and many of the
pro-inflammatory interleukins (IL). Consequently, modulation of JAK1 is a
therapeutic target for the treatment of ulcerative colitis.
In this study the safety of GSK2586184 will be assessed in patients with
ulcerative colitis. A first impression about efficacy is aimed at. The study
will be conducted as a single center study in the Netherlands.
Study objective
Primary: Safety and tolerability.
Secondary: Clinical and endoscopic remission, symptomatic clinical remission,
clinical response, mucosal healing, health related QoL, CRP, faecal
calprotectin, pharmacokinetics.
Study design
Open-label non-comparative phase I study. Treatment with GSK2586184 400 mg bid
orally for 8 weeks.
Approx. 15 patients.
Intervention
Treatment with GSK2586184.
Study burden and risks
Risk: adverse events of study treatment.
Burden: 6 visits in approx. 12 weeks. Duration 1-4h.
Blood draws every visit (approx. 40 ml/occasion).
Physical examination every visit.
Sigmoidoscopy 2x.
ECG every visit.
Questionnaire quality of life 3x.
Diary times of intake study medication.
Huis Ter Heideweg 62
Zeist 3705 LZ
NL
Huis Ter Heideweg 62
Zeist 3705 LZ
NL
Listed location countries
Age
Inclusion criteria
* Male or female, between 18 and 75 years of age inclusive.
* Moderate to severely active UC at least 6 months prior to Screening confirmed by colonoscopy or sigmoidoscopy with video recording, and biopsy.
* Mayo score of 6 to 12 points and endoscopy sub score of 2 to 3 at screening, despite concurrent treatment (see protocol page 20 for details).
* Females of non-childbearing potential. See protocol page 21 for details.
* Female partners of child-bearing potential of male participants must agree to use
acceptable contraception methods.
Exclusion criteria
* Fulminant UC, or UC limited to rectum.
* Previous colonic surgery, histological evidence of colonic dysplasia, or bowel stricture.
* Live vaccination within 4 weeks before the first dose of study medication, or a live vaccination planned during the course of the study.
* Acute or chronic infections (see protocol page 22 for details).
* Females of child-bearing potential.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-001369-18-NL |
| CCMO | NL45992.018.13 |
| Other | www.gsk-clinicalstudyregister.com |