To assess efficacy and safety of tofacitinib in the treatment of chronic, recurrent and/or antibiotic refractory pouchitis.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the proportion of patients in clinical and endoscopic
remission at week 8.
Secondary outcome
The main secondary endpoints are changes in histologic disease activity, immune
cell infiltration, gene expression of inflammatory cytokines and changes in the
microbiome.
Background summary
Ileal pouch-anal anastomosis (IPAA) is the standard of care for patients with
ulcerative colitis (UC) who require colectomy. Up to 50% of these IPAA patients
will develop at least one episode of pouchitis(1, 2) and up to 20% will develop
a chronic phenotype. The aetiology of pouchitis remains unknown. An overlap
with recurrence of UC has been suggested, since pouchitis is rarely seen in
patients with IPAA for other indications, such as familial adenomatous
polyposis (FAP). With symptoms such as increased stool frequency, urgency and
abdominal cramps, quality of life in pouchitis patients is considerably
impaired(3). Furthermore, pouchitis accounts for 24% of all late-onset pouch
failures as current therapies are not always effective(4). Therefore, new
therapies that can offer symptom resolution as well as endoscopic and
histologic remission are essential. Tofacitinib, an oral small molecule JAK1
and JAK3 inhibitor, is effective for induction and maintenance of remission in
UC(5). Considering the immunological component of chronic pouchitis, in which
the inflammatory pathway might be similar to that seen in UC since pouchitis
rarely occurs in FAP patients(6), effective immunosuppressant drugs such as
tofacitinib potentially offer a new treatment modality for this treatment
refractory population.
The aim of this proposal is to assess the efficacy of tofacitinib in the
treatment of chronic, recurrent and/or antibiotic refractory pouchitis, as well
as observing changes in endoscopic and histologic appearance and in multi-omics
analyses before and after treatment with tofacitinib.
Study objective
To assess efficacy and safety of tofacitinib in the treatment of chronic,
recurrent and/or antibiotic refractory pouchitis.
Study design
This study will be a single-arm, open-label, proof of concept trial.
Intervention
Treatment with Tofacitinib 10mg, two times a day, for 8 weeks.
Study burden and risks
Patients will have a total follow-up time of 12 weeks, in which five outpatient
clinic visits and one telephone consult are scheduled. Blood samples will be
drawn five times. Endoscopic assessment of the pouch will be done at baseline
and at week 8. During this procedure, biopsies will be taken. A pouchoscopy is
regarded as a safe procedure with a very small risk of complications.
Tofacitinib will be given to patients included in this trial. In previous
research, tofacitinib proved to be effective in the treatment of moderately to
severely active UC(5). Tofacitinib has been studied for more than 10 years in
patients with rheumatoid arthritis. In these studies, tofacitinib showed a
similar safety profile as biologic agents, apart from a higher incidence rate
of herpes zoster infection(7, 8).
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
1. Subject has a history of ileal pouch anal anastomosis (IPAA) for UC, all
stages completed at least 6 months prior to day one of the start of the study.
2. Subject has chronic, recurrent and/or antibiotic refractory pouchitis,
defined as a PDAI >= 7 (or mPDAI >= 5 if histology is pending) , with either
- >= 2 recurrent pouchitis episodes within 1 year prior to screening,
necessitating treatment with antibiotics or other prescription, or;
- Requiring maintenance antibiotic therapy for >= 4 weeks to maintain clinical
remission and a history of at least two attempts in the last 24 months to stop
this therapy, resulting in a relapse of the pouchitis episodes.
Exclusion criteria
1. Pouchitis due to surgery related conditions (such as an abscess, fistula, or
sinus of the pouch).
2. Absence of a previous pelvic MRI to assess secondary causes of pouchitis.
3. Irritable pouch syndrome (symptoms without evidence of pouchitis on
endoscopy and histology).
4. Mechanical complications of the pouch (e.g. pouch stricture or pouch
fistula).
5. Diverting ileostomy.
6. Positive stool sample for C. difficile, enteric pathogens, pathogenic ova or
parasites at screening.
7. Active herpes zoster infection or history of disseminated zoster infection.
8. Evidence of an active infection during screening, or known history of
chronic HBV, HCV, HIV infection, or if subject is immunodeficient.
9. Active or latent infection with Mycobacterium tuberculosis (TB), regardless
of treatment history.
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 | EUCTR2020-002695-12-NL |
| CCMO | NL71383.018.20 |