E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic, recurrent and/or antibiotic refractory pouchitis in patients with ulcerative colitis |
Chronische, recidiverende en/of antibiotica refractaire pouchitis in patiënten met colitis ulcerosa |
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E.1.1.1 | Medical condition in easily understood language |
Pouchitis in patient with ulcerative colitis |
Pouchitis in patiënten met colitis ulcerosa |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess efficacy and safety of tofacitinib in the treatment of chronic, recurrent and/or antibiotic refractory pouchitis. |
Om de werkzaamheid en veiligheid van tofacitinib te beoordelen bij de behandeling van chronische, recidiverende en / of antibioticum-refractaire pouchitis. |
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E.2.2 | Secondary objectives of the trial |
histologic disease activity, immune cell infiltration, gene expression of inflammatory cytokines and changes in the microbiome. |
histologische ziekteactiviteit, immuuncelinfiltratie, genexpressie van inflammatoire cytokines en veranderingen in het microbioom. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 , 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. |
1. Proefpersoon heeft een ileale pouch-anale anastomose (IPAA) voor colitis ulcerosa, alle stadia voltooid ten minste 6 maanden voor dag 1 van de start van de studie. 2. Proefpersoon heeft chronische, recidiverende en/of antibiotica refractaire pouchitis, gedefinieerd als een PDAI ≥ 7, met of - ≥ 2 recidiverende pouchitis episodes binnen 1 jaar voor start screening, waardoor behandeling met antibiotica of andere middelen nodig is, of; - Continu gebruik van antibiotica onderhoudstherapie gedurende ≥ 4 weken om klinisch in remissie te blijven, en daarbij ten minste 2 pogingen in de laatste 24 maanden om de therapie te staken, wat heeft geresulteerd in een recidief van de pouchitis klachten. |
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E.4 | Principal 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. |
1. Pouchitis t.g.v. operatie gerelateerde aandoeningen (zoals abces, fistel, sinus van de pouch) 2. Geen eerdere MRI van de pouch om secundaire oorzaken van pouchitis aan te tonen. 3. Prikkelbare pouch syndroom (symptomen suggestief voor pouchitis, zonder tekenen van inflammatie bij endoscopie en histologie). 4. Mechanische complicaties van de pouch (strictuur of fistel). 5. Eindstandig ileostoma. 6. Ontlasting positief voor C. difficile, enterische pathogenen, ova of parasieten bij screening. 7. Actieve herpes zoster infectie of voorgeschiedenis met een gedissemineerde zoster infectie. 8. Aanwijzingen van een actieve infectie tijdens screening, of bekende voorgeschiedenis met HBV, HCV, HIV, of immunodeficientie. 9. Actieve of latente infectie met Mycobacterium tuberculosis (TB), onafhankelijk van eerdere behandelingen. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects with chronic, recurrent and/or antibiotic refractory pouchitis achieving clinical relevant remission after 8 weeks of treatment with tofacitinib. Clinical relevant remission is defined as a PDAI score < 7 and a reduction of the overall score by ≥ 3 points from baseline. |
Proportie proefpersonen met chronische, recidiverende en / of antibioticum-refractaire pouchitis die klinisch relevante remissie bereiken na 8 weken behandeling met tofacitinib. Klinisch relevante remissie wordt gedefinieerd als een PDAI-score <7 en een verlaging van de algehele score met ≥ 3 punten ten opzichte van baseline. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 8 of treatment |
Week 8 van behandeling |
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E.5.2 | Secondary end point(s) |
• Proportion of subjects achieving mPDAI < 5 and a reduction of the overall score by ≥ 2 points from baseline to week 8 and week 12. • Proportion of subjects achieving a partial response after 8 weeks, defined as a reduction in PDAI ≥ 2 points from baseline. • Proportion of subjects in sustained antibiotic-free remission and no need for rescue therapy until week 12. • Change in total PDAI. • Change in the endoscopic subscore of the PDAI at week 8, compared to baseline. • Change in histologic subscore of the PDAI at week 8, compared to baseline. • Time to clinical relevant remission. • Time to relapse. • Total number of patients in deep remission, defined as a PDAI of 0 at week 8. • Proportion of subjects not requiring further antibiotic treatment at week 8 and week 12. • Change in total scores of Inflammatory Bowel Disease Questionnaire (IBDQ) at week 8, compared to baseline. • Change in Cleveland Global Quality of Life (CGQL) at week 8, compared to baseline. • Change in SF-36 from baseline to week 8. • Incidence and severity of adverse events up to 84 days after initiating treatment.
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• Proportie proefpersonen dat een mPDAI <5 bereikt en een verlaging van de totale score met ≥ 2 punten ten opzichte van baseline tot week 8 en week 12. • Proportie proefpersonen dat na 8 weken een gedeeltelijke respons bereikt, gedefinieerd als een verlaging van PDAI ≥ 2 punten ten opzichte van baseline. • Proportie proefpersonen met aanhoudende antibioticavrije remissie, en die tot 12 weken geen andere behandeling nodig hebben. • Verandering in totale PDAI. • Verandering in de endoscopische subscore van de PDAI in week 8, vergeleken met baseline. • Verandering in histologische subscore van de PDAI in week 8, vergeleken met baseline. • Tijd tot klinisch relevante remissie. • Tijd tot recidief van pouchitis. • Totaal aantal patiënten in diepe remissie, gedefinieerd als een PDAI van 0 in week 8. • Proportie proefpersonen dat in week 8 en week 12 geen verdere antibioticabehandeling nodig heeft. • Verandering in totale scores van de Inflammatory Bowel Disease Questionnaire (IBDQ) in week 8, vergeleken met baseline. • Verandering in Cleveland Global Quality of Life (CGQL) in week 8, vergeleken met baseline. • Verandering in SF-36 van baseline tot week 8. • Incidentie en ernst van bijwerkingen tot 84 dagen na aanvang van de behandeling. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Changes in histologic inflammation |
Veranderingen in histologische inflammatie |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |