To investigate inflammatory markers in blood en colon biopsies of UC patients who respond to treatment with tofacitinib within the OCTAVE induction study (METC2012_072) and patients who do not show response to treatment within the OCTAVE induction…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
inflammatory infiltrate, transcription of inflammatory genes, phosphorylation
of Jak/Stat proteins.
Secondary outcome
none
Background summary
Currently tofacitinib, a selective JAK1-, JAK2-, JAK3- and TYK2-inhibitor, is
under development as a potential therapy for patients with moderately to
severly active ulcerative colitis. Tofacitinib inhibits JAK1 and JAK3, which
blocks cytokine signalling via teh common gamma chain. The common gamma chain
contains receptors for several cytokines ( IL2, -4, -7, -9, -15 and -21) that
are integrall to lymphocyte activation and proliferation and function during
the adaptive immune response. In addition, JAK1 attenuates pro-inflammatory
cytokines such as interferon gamma that are integral foor monocyte
differentiation during the innate immune response. It remains unclear whether
the efficacy of tofacitinib is mainly attributed to JAK1 or JAK3, therefore it
is of great value to investigate the effect of tofacitinib in colon biopies and
blood.
This is the first time a Jak-inhibitor is being investigated in a phase III
trial with UC patients in the AMC. A future trial with a selective
JAK1-inhibitor will follow in which inflammatory markers will be assessed,
therefore it is of great relevance that this unique material from the OCTAVE
trialis is collected for a comparative analysis. This will allow us to collect
scientific evidence to determine the development of a more selective
JAK-inhibitor as a potential new treatment for ulcerative colitis.
Study objective
To investigate inflammatory markers in blood en colon biopsies of UC patients
who respond to treatment with tofacitinib within the OCTAVE induction study
(METC2012_072) and patients who do not show response to treatment within the
OCTAVE induction study en therefore will be treated in the OCTAVE Open Label
study (METC2012_075)
Study design
Prospective observational trial
Study burden and risks
A colonoscopy is a safe procedure, however in some cases (1 in 10.000) a
hemorrhage or perforation of the intestinal wall can occur. Most of these
complications occur during the colonoscopy, although they can be treated during
the procedure as well. There are no risks for the withdrawal of blood samples,
because they will be collected simultaneously with the screening of the OCTAVE
trial at two timepoints.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
1. patients (*18 years) with ulcerative colitis with an indication to start Tofacitinib within the OCTAVE induction study (METC2012_072) and responding to this therapy
2. patients (*18 years) with ulcerative colitis with an indication to start Tofacitinib within the Open Label study (METC_075), after having been defined as a non-responder within the participation in the OCTAVE Induction study (METC2012_072)
Exclusion criteria
subjects without previous treatment for UC
Design
Recruitment
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 |
|---|---|
| CCMO | NL45304.018.13 |