Inflammatory bowel disease
Conditions
Interventions
Tofacitinib 2 x 5 mg twice daily
Sponsors
Academisch Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Subject must be at least 18 years of age., 2. Males and females with a documented diagnosis of UC * 4 months prior to entry into the study. A biopsy report supporting the diagnosis must be available in the source documents., 3. Subjects with moderately to severely active UC as defined by a total Mayo score of * 6 with an endoscopic (sigmoidoscopy) subscore of * 2 on the Mayo score determined within 7 days of starting the study treatment (tofacitinib)., 4. Subjects must have failed or be intolerant (discontinued the medication due to an adverse event as determined by the investigator) of at least one of the following treatments for UC:, - Oral corticosteroids, - Azathioprine or 6-mercaptopurine (6-MP)., - Anti-TNF therapy: infliximab, adalimumab or golimumab, 5. No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB) as defined by negative QuantiFERON*-TB Gold (QFT-G) In-Tube test and a chest radiograph, taken at or within the 3 months prior to a given screening visit, without changes suggestive of active TB infection as determined by a qualified radiologist. , 6. If a subject has previously received an adequate course of therapy for either latent (9 months of isoniazid in a locale where rates of primary multi-drug TB resistance are less than 5% or an acceptable alternative regimen) or active (acceptable multi-drug regimen) TB infection, neither a QFT-G test nor a PPD test is needed, but a chest radiograph must still be obtained if not performed within 3 months prior to a given Screening visit. , 7. Female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 4 weeks after the last dose of assigned treatment. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active., 8. Women of childbearing potential must have a negative pregnancy test prior to study enrolment., 9. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, daily diary listing, and other study procedures.
Exclusion criteria
Exclusion criteria: 1. Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical findings suggestive of Crohn*s disease., 2. Subjects without previous treatment for UC (ie, treatment-naïve)., 3. Subjects displaying clinical signs of fulminant colitis or toxic megacolon., 4.Subjects with evidence of colonic adenomas or dysplasia. However, subjects with prior history of adenomatous polyps will be eligible if the polyps have been completely removed and the subjects are free of polyps at baseline., 5. Subjects at risk for colorectal cancer must have a Colonoscopy. Colonoscopy report and pathology report (if biopsies are obtained) must be available in the source document * If the subject is >50 years of age, a colonoscopy within 10 years of the screening visit is required to exclude adenomatous polyps. Subjects whose adenomas have been completely excised at baseline will be eligible., * If the subject has extensive colitis for >8 years or disease limited to left side of colon (ie, distal to splenic flexure) for >10 years, regardless of age, a colonoscopy within 1 year of the screening visit is required to survey for dysplasia. Subjects with dysplasia or cancer identified on biopsies will be excluded., 6. Subjects who have had surgery for UC or in the opinion of the Investigator, are likely to require surgery for UC during the study period., 7. Subjects who have positive stool examinations for enteric pathogens, pathogenic ova or parasites, or Clostridium difficile toxin at screening. , 8. Subjects with clinically significant infections currently or within 6 months of baseline(eg those requiring hospitalization or parental antomicrobial therapy for oppurtunistic infection , a history of any infection requiring antimicrobial therapy within 2 weeks of baseline, or a history of any infection otherwise judged by the investigator to have the potential for exacerbation by participation in the study., 9. Subjects with a history of more than one episode of herpes zoster, a history of disseminated herpes zoster or disseminated herpes simplex., 10. Subjects infected with human immunodeficiency virus (HIV) or hepatitis B or C viruses (Subjects with negative HBV surface antigen but positive HBV core antibody must have further testing for HBV surface antibody and if negative for HBV surface antibody, will be excluded from study enrollment). , 11. Subjects who have been vaccinated with live or attenuated vaccine within 6 weeks of baseline or scheduled to receive these vaccines during study period or within 6 weeks after last dose of study medication., 12. Subjects with history of any lymphoproliferative disorder (such as EBV-related lymphoproliferative disorder, as reported in some subjects on other immunosuppressive drugs), history of lymphoma, leukemia, myeloproliferative disorders, multiple myeloma, or signs and symptoms suggestive of current lymphatic disease., 13. Subjects with malignancies or a history of malignancies, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin., 14. Subjects with a history of bowel surgery within 6 months prior to baseline., 15. Subjects with significant trauma or major surgery within 4 weeks of screening visit., 16. Subjects likely to require any type of surge
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To investigate the efficacy of twice daily doses of tofacitinib (10 mg bid) to decrease histological inflammation after 8 weeks of treatment in patients with moderate to severely active ulcerative colitis measured by: Median change in inflammatory infiltrates at week 8 in 2 colon biopsies as assessed by the Robarts Histopathology Index [Mosli, Gut, 2015] and the Geboes index [Geboes, Gut, 2000], by an independent GI pathologist. | — |
Secondary
| Measure | Time frame |
|---|---|
| - Median change in symptoms as measured by the Simple Clinical Colitis Activity Index (SCCAI) at weeks 0, 2, 4 and 8. - Median change in high sensitivity CRP and fecal calprotectin after treatment with tofacitinib for 8 weeks. - Median improvement of endoscopic disease severity measured by the Mayo endoscopy score.Proportion of patients reaching mucosal healing (Mayo 0/1) after 8 weeks of tofacitinib. Proportion of subjects in endoscopic remission at Week 8. Endoscopic remission is defined by Mayo endoscopic subscore of 0. - Incidence and severity of adverse events up to 84 days after initiating treatment. - Proportion of subjects achieving clinical response at Week 8. Clinical response is defined by a decrease from baseline in Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or absolute subscore for rectal bleeding of 0 or 1. - The proportion of subjects in clinical remission at Week 8. Clinical remission is defined by a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point. - The proportion of subjects in symptomatic remission at Week 8. Symptomatic remission is defined by a total Mayo score of 2 points or lower, with no individual subsocre exceeding 1 point, and both rectal bleeding and stool frequency subcore of 0. - The proportion of subjects achieving deep remission at Week 8. Deep remission is defined by a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point and a zero on both endoscopic and rectal bleeding subscores. | — |
Countries
Netherlands
Outcome results
None listed