Moderate to Severe Ulcerative Colitis (UC) MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856
Conditions
Interventions
Product Name: Ritlecitinib
Product Code: PF-06651600
Pharmaceutical Form: Capsule
INN or Proposed INN: PF-06651600
Current Sponsor code: PF-06651600
Other descriptive name: PF-06651600
Concentration u
Sponsors
Pfizer Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: Age and Sex: 1.At least =18 years of age (or the minimum country-specific age of consent if >18 years of age) at the Screening visit. •Refer to Appendix 4 for reproductive criteria for female (Section 10.4.2) participants. Type of Participant and Disease Characteristics: 2.Documented onset of UC =3 months prior to baseline. A report supporting disease duration and extent (eg, proctosigmoiditis, left sided colitis, or pancolitis) based upon prior endoscopy including a biopsy report must be available in the source documentation prior to the Induction baseline visit. 3.Moderately to severely active UC defined as •active disease beyond the rectum (active disease >15 cm from the anal verge at the screening endoscopy) and •by a modified Mayo score between 5 and 9, inclusive, with a rectal bleeding subscore =1 and an endoscopic subscore =2, determined at the Baseline visit The endoscopic subscore will be assessed centrally and must be available at the Induction baseline visit to derive the modified Mayo Score. Endoscopic assessment (colonoscopy or flexible sigmoidoscopy [if a colonoscopy was performed within 12 months before screening and the extent of disease is limited to left-sided colitis]) performed within 10 days of the Baseline visit will be accepted. Refer to exclusion criterion 3 for participants considered at risk for colorectal cancer for whom colonoscopy is required. 4.Currently receiving any of the following treatments for UC are eligible, providing they have been and that they are anticipated to be on stable dose for the specified period of time: •Oral 5ASA or sulfasalazine: stable dose for at least 4 weeks prior to Induction baseline and during the duration of the treatment phase. If oral 5ASA treatment has been recently discontinued, it must have been stopped for at least 2 weeks prior to Induction baseline. •Oral corticosteroids (prednisone equivalent up to 25 mg/day; budesonide up to 9 mg/day; (see Appendix 15, Section 10.15): stable dose for at least 2 weeks prior to Induction baseline and during the duration of the treatment phase until initiation of corticosteroid treatment tapering. If oral corticosteroids have been recently discontinued, they must have been stopped at least 2 weeks prior to Induction baseline. Decreases in steroid use due to steroid-related adverse reactions are allowed. 5.Must have an inadequate response to, loss of response to, or intolerance to at least one conventional therapy for UC: •IV or oral corticosteroids; •Immunosuppressants (AZA, 6MP, or MTX); •TNF inhibitors (eg, infliximab, adalimumab, or golimumab); •Integrin inhibitors (eg, vedolizumab). •IL12/23 inhibitor (eg, ustekinumab). •JAK inhibitors (eg, tofacitinib). NOTE: if participant is intolerant to a JAK inhibitor, they must not be included (See exclusion criterion 18). Note: the washout period for these medications is presented in Section 5.2 (exclusion criterion 17). 6.Willing and able to comply with scheduled visits (including telemed/home visits, where allowed), treatment plan, laboratory tests, daily bowel movement diary, and other study procedures. Informed Consent: 7.Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions: Medical Conditions Pertaining to UC 1.Presence / evidence of •indeterminate colitis •microscopic colitis •ischemic colitis •infectious colitis •primary sclerosing cholangitis •colonic dysplasia •adenomas or neoplasia •clinical findings suggestive of Crohn’s disease (eg, fistulae, granulomas on biopsy); •clinical signs of fulminant colitis or toxic megacolon 2.History of •bowel surgery within 6 months prior to Baseline, •known colonic stricture •colonic or small bowel obstruction or extensive small bowel resection (> 100 cm), or short bowel syndrome •colonic or small bowel stoma •hospitalized for UC related reason(s) within 4 weeks of Induction baseline visit. 3.Meeting either of the 2 criteria below are considered at risk for colorectal cancer. The colonoscopy and pathology reports (if biopsies obtained) must be available in the source documentation: •If the participant is =50 years of age, and a colonoscopy has not been performed within 10 years of the first dose of study intervention, the colonoscopy at the screening visit is required to exclude adenomatous polyps. Participants with adenomatous polyps identified on screening endoscopy will be eligible after complete polypectomy and if no further short-term endoscopic follow-up is required per local guidelines. •If the participant has had extensive (ie, greater than left sided) colitis for =8 years or disease limited to left side of colon (ie, distal to splenic flexure) for =10 years, regardless of age, and a colonoscopy has not been performed within 12 months of the first dose of study intervention, the colonoscopy at the screening visit is required to survey for dysplasia. Participants with dysplasia or cancer identified on biopsies will be excluded. 4.Positive stool examinations for enteric pathogens, pathogenic ova or parasites, or presence of active enteric infections: known pathogenic bacterial, parasitic, fungal infections, including Clostridium difficile toxin at screening. Medical Conditions, Infection History 5.General Infection History •clinically significant infections defined as those requiring hospitalization; opportunistic infections; requiring parenteral antimicrobial, antiviral (including biologic treatment), antiparasitic, antiprotozoal, or antifungal therapy, currently or within 6 months of Baseline •history of any infection requiring oral antimicrobial, antiviral (including biologic treatment), antiparasitic, antiprotozoal, or antifungal therapy within 2 weeks of Induction Baseline •history of any infection or chronic/recurrent infections otherwise judged by the investigator to have the potential for exacerbation by participation in the study. 6.Evidence or history of untreated, currently treated or inadequately treated active or latent infection with Mycobacterium tuberculosis (TB) as evidenced by the following: •IGRA test: a positive QuantiFERON® TB Gold Plus (QFT-G, completed by central laboratory) or a positive or borderline T-SPOT®.TB (performed at local laboratory in Japan or those countries where local guidance require T-SPOT®.TB testing) during screening. If the IGRA test results are indeterminate/borderline, the test should be repeated. If the results of the repeat test are indeterminate/borderline, a purified protein derivative (PPD) test may be substituted for the IGRA test only with the approval from the Pfizer medical monitor on a case-by-ca
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •Induction phase: To demonstrate whether ritlecitinib is superior to placebo, in participants with moderately to severely active UC, at Week 8 (I-8). •Maintenance phase: To evaluate the maintenance of efficacy of ritlecitinib over placebo, in participants with moderately to severely active UC, at Week 52 (M-44).;Secondary Objective: •To evaluate the efficacy of ritlecitinib over placebo, in participants with moderately to severely active UC, on additional efficacy endpoints at Week 8 (I-8) and Week 52 (M 44). •To compare the efficacy of ritlecitinib versus placebo, in participants with moderately to severely active UC, on additional efficacy endpoints over time. •To compare the effect of ritlecitinib versus placebo on PROs over time. •To compare the effect of ritlecitinib versus placebo on disease biomarkers over time. •To characterize the safety of ritlecitinib versus placebo in participants with moderately to severely active UC;Primary end point(s): Induction Phase Clinical Remission Maintenance Phase Clinical Remission;Timepoint(s) of evaluation of this end point: Induction Phase Week 8 Maintenance Phase Week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Induction phase: •Endoscopic improvement at Week 8 (I-8). •Endoscopic-histologic mucosal improvement at Week 8 (I-8) . Maintenance phase: •Endoscopic improvement at Week 52 (M-44). •Steroid-free clinical remission at Week 52 (M-44). •Endoscopic-histologic mucosal improvement at Week 52 (M 44).;Timepoint(s) of evaluation of this end point: Timepoints are as specified above | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Czechia, Denmark, France, Germany, Greece, India, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Norway, Poland, Russian Federation, Serbia, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trials.gov Call Centre
Pfizer Inc.
Outcome results
None listed