A Study of Tofacitinib in Patients With Ulcerative Colitis in Stable Remission

A PHASE 3B/4, MULTI-CENTER, DOUBLE-BLIND, RANDOMIZED, PARALLEL GROUP STUDY OF TOFACITINIB (CP-690,550) IN SUBJECTS WITH ULCERATIVE COLITIS IN STABLE REMISSION

This study is a follow up study for subjects with Ulcerative Colitis (UC) in stable remission designed to evaluate flexible dosing of CP-690,550.

Study Overview

• Status: Terminated
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: CP-690,500 5 mg; Drug: CP-690,550 10 mg

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven (University Hospital Leuven), Campus Gasthuisberg
• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre - University Hospital
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Royal University Hospital
• Czechia
  • Strakonice, Czechia, 386 01
    • Nemocnice Strakonice a.s.
• France
  • Nantes, France, 44093
    • Chu Hotel Dieu
  • Pessac, France, 33600
    • CHU de Bordeaux Hôpital Haut Lévêque
• Germany
  • Kiel, Germany, 24105
    • Universitaetsklinikum Schleswig-Holstein
• Hungary
  • Budapest, Hungary, 1125
    • Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak
  • Budapest, Hungary, 1136
    • Pannonia Maganorvosi Centrum Kft.
  • Gyula, Hungary, 5700
    • Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaz Endoszkopos Laboratorium
• Italy
  • CZ
    • Catanzaro, CZ, Italy, 88100
      • Università "Magna Graecia" di Catanzaro
• Japan
  • Chiba, Japan, 285-8741
    • Toho University Sakura Medical Center
  • Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital
  • Osaka, Japan, 545-8586
    • Osaka Metropolitan University Hospital
  • Tokyo, Japan, 160-8582
    • Keio University Hospital
  • Aichi
    • Nagakute, Aichi, Japan, 480-1195
      • Aichi Medical University Hospital
  • Fukuoka
    • Chikushino, Fukuoka, Japan, 818-8502
      • Fukuoka University Chikushi Hospital
    • Kurume, Fukuoka, Japan, 830-0011
      • Kurume University Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-0033
      • Hokkaido P.W.F.A.C Sapporo-Kosei General Hospital
  • Osaka
    • Takatsuki-shi, Osaka, Japan, 569-8686
      • Osaka Medical and Pharmaceutical University Hospital
  • Shiga
    • Otsu, Shiga, Japan, 520-2192
      • Shiga University of Medical Science Hospital
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8519
      • Tokyo Medical and Dental University Hospital, Faculty of Medicine
    • Hachioji, Tokyo, Japan, 192-0032
      • Tokai University Hachioji Hospital
    • Minato-ku, Tokyo, Japan, 108-8642
      • Kitasato University Kitasato Institute Hospital
    • Shinagawa-ku, Tokyo, Japan, 142-8666
      • Showa University Hospital
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of, 11923
    • Hanyang University Guri Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 02447
    • Kyung Hee University Hospital
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academic Medical Centre
• New Zealand
  • Christchurch, New Zealand, 8011
    • Christchurch Hospital (Canterbury District Health Board)
  • Dunedin, New Zealand, 9016
    • Southern District Health Board
  • Auckland
    • Takapuna, Auckland, New Zealand, 0620
      • North Shore Hospital (Waitemata District Health Board)
• Poland
  • Sopot, Poland, 81-756
    • Endoskopia Sp. z o.o.
  • Wroclaw, Poland, 53-114
    • LexMedica
• Russian Federation
  • Moscow, Russian Federation, 123423
    • Federal State Budgetary Institution "State Scientific Centre of Coloproctology
  • Novosibirsk, Russian Federation, 630007
    • LLC Novosibirskiy Gastrocenter
  • Novosibirsk, Russian Federation, 630117
    • Federal State Budgetary Scientific Institution "Scientific Research Institute of Physiology
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Centre of Serbia, Clinic for Gastroenterology and Hepatology
  • Belgrade, Serbia, 11000
    • Clinical Hospital Centre Zvezdara
  • Belgrade, Serbia, 11000
    • Military Medical Academy, Clinic for Gastroenterology and Hepatology
  • Kragujevac, Serbia, 34000
    • Clinical Center Kragujevac
  • Zrenjanin, Serbia, 23000
    • General Hospital "Djordje Joanovic"
• Slovakia
  • Bratislava, Slovakia, 851 01
    • Medak s.r.o.
  • Nitra, Slovakia, 949 01
    • KM Management spol. s.r.o.
  • Presov, Slovakia, 080 01
    • Gastro I., s.r.o., Gastroenterologicka ambulancia
• South Africa
  • Cape Town
    • Claremont, Cape Town, South Africa, 7708
      • Kingsbury Hospital
  • Johannesburg
    • Soweto, Johannesburg, South Africa, 2013
      • Chris Hani Baragwanath Academic Hospital
  • Johannesburg, Gauteng
    • Soweto, Johannesburg, Gauteng, South Africa, 2013
      • Wits Clinical Research (WCR) Bara Site, Chris Hani Baragwanath Academic Hospital
  • Western CAPE
    • Paarl, Western CAPE, South Africa, 7646
      • Endocare Research Centre
    • Panorama, Western CAPE, South Africa, 7500
      • Panorama MediClinic
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
• Ukraine
  • Chernivtsi, Ukraine, 58001
    • Regional Municipal Non-Profit Enterprise "Chernivtsi Regional Clinical Hospital" Surgery Departm
  • Kyiv, Ukraine, 01030
    • Kyiv Municipal Clinical Hospital #18
  • Uzhgorod, Ukraine, 88009
    • MI Uzhgorod Regional Hospital
  • Vinnytsia, Ukraine, 21005
    • Vinnytsia Regional Clinical Hospital for War Veterans, Therapeutics Dept. No. 2
• United Kingdom
  • Avon
    • Bristol, Avon, United Kingdom, BS2 8HW
      • University Hospitals Bristol NHS Foundation Trust
• United States
  • Alabama
    • Mobile, Alabama, United States, 36606
      • Surgicare of Mobile
    • Mobile, Alabama, United States, 36608
      • Alabama Medical Group, P.C.
  • California
    • San Diego, California, United States, 92103
      • Clinical Applications Laboratories, Inc.
  • Connecticut
    • Bristol, Connecticut, United States, 06010
      • Connecticut Clinical Research Institute
    • Bristol, Connecticut, United States, 06010
      • Bristol Hospital
    • Plainville, Connecticut, United States, 06062
      • Central Connecticut Endoscopy Center
  • Florida
    • Port Orange, Florida, United States, 32127
      • Advanced Medical Research Center
    • Zephyrhills, Florida, United States, 33542
      • Florida Medical Clinic, P.A.
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton-O'Neil Clinical Research Center, Digestive Health
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • MGG Group Co., Inc., Chevy Chase Clinical Research
    • Chevy Chase, Maryland, United States, 20815
      • Chevy Chase Endoscopy Center
  • Michigan
    • Chesterfield, Michigan, United States, 48047
      • Clinical Research Institute of Michigan, LLC
    • Macomb, Michigan, United States, 48044
      • Eastside Endoscopy Center
    • Troy, Michigan, United States, 48098
      • Clinical Research Institute of Michigan, LLC
  • New York
    • Lake Success, New York, United States, 11042
      • NYU Langone Long Island Clinical Research Associates
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center Research Pharmacy/ Milstein Hospital
  • Ohio
    • Mentor, Ohio, United States, 44060
      • Great Lakes Gastroenterology Research, LLC
  • Texas
    • Houston, Texas, United States, 77030
      • Memorial Hermann Hospital
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston (UTHealth)- McGovern Medical School
    • Tyler, Texas, United States, 75701
      • Tyler Research Institute, LLC
    • Tyler, Texas, United States, 75701
      • Christus Trinity Mother Frances Endoscopy Center
  • Utah
    • Salt Lake City, Utah, United States, 84102
      • Alpine Medical Group
    • Salt Lake City, Utah, United States, 84107
      • Wasatch Clinical Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Currently enrolled in Study A3921139 receiving CP-690,550 10 mg BID for at least 2 years consecutively.
• In stable remission on CP-690,550 10 mg BID
• Agree to use highly effective contraception
• Negative pregnancy test
• Comply with visits, treatments, lab tests, diary and other study procedures
• Signed and dated informed consent document.

Exclusion Criteria:

• Subjects who were initially assigned to tofacitinib 10 mg BID at baseline of Study A3921139 whose tofacitinib dose was reduced to 5 mg BID due to safety or efficacy.
• Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis or findings suggestive of Crohn's disease
• Likely to require surgery for ulcerative colitis during study
• Expected to receive any prohibited medication
• Expected to receive live or attenuated virus vaccination during study
• Women who are pregnant or breastfeeding or planning to become pregnant during the study
• Evidence of colonic malignancy or any dysplasia
• Acute or chronic medical or psychiatric condition that may increase risk of participation
• Investigator site staff member
• Subjects likely to be uncooperative or unable to comply with study procedures
• Participation in other studies involving investigational drugs during study

• Subjects with any of the following risk factors for pulmonary embolism at baseline as defined by EMA's PRAC:

  • has heart failure;
  • has inherited coagulation disorders;
  • has had venous thromboembolism, either deep venous thrombosis or pulmonary embolism;
  • is taking combined hormonal contraceptives or hormone replacement therapy;
  • has malignancy (association is strongest with cancers other than non-melanoma skin cancers);
  • is undergoing major surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CP-690,550 5 mg; CP-690,550 5 mg tablet by mouth twice a day (BID)	Drug: CP-690,500 5 mg; CP-690,550 5 mg tablet BID
Experimental: CP-690,550 10 mg; CP-690,550 10 mg BID	Drug: CP-690,550 10 mg; CP-690,550 10 mg tablet BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Remission Based on Modified Mayo Score at Month 6	Remission as per modified mayo score was defined as an endoscopic subscore of 0 or 1, stool frequency subscore of 0 or 1, and rectal bleeding subscore of 0 at Month 6. Modified mayo score consisted of 3 components: stool frequency subscore, rectal bleeding subscore and endoscopic subscore: higher scores for each score = more severe disease. These scores were summed up to give a total modified mayo score range of 0 to 9; where higher scores indicating more severe disease.	Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Modified Partial Mayo Score at Months 1, 3 and 6	Modified partial mayo scores consisted of 2 subscores: stool frequency and rectal bleeding with each subscore graded from 0 to 3 with higher scores indicating more severe disease. Individual subscores were summed up to give a total Modified partial mayo score ranges from 0 (normal or inactive disease) to 6 (severe disease) with higher scores indicating more severe disease.	Baseline, Months 1, 3 and 6
Time to Loss of Remission Based on Modified Mayo Score Using Kaplan-Meier Method	Time to loss of remission(flare): time from first drug administration until time of meeting loss of remission criteria based on modified mayo score. Loss of remission: meeting at least (>=)1 criteria: increase from Baseline in rectal bleeding subscore by >=1 point and increase in endoscopic subscore by >=1 point; increase from Baseline in rectal bleeding subscore by >=2 points and endoscopic subscore >0; increase in stool frequency subscore by >=2 points and increase in endoscopic subscore by >=1 point; increase in endoscopic subscore by >=2 points. Modified mayo score included 3 components: stool frequency, rectal bleeding and endoscopic subscores: Modified mayo score included 3 components: stool frequency, rectal bleeding and endoscopic subscores, each subscore graded from 0 to 3 with higher scores for each score=more severe disease. All scores summed up to give total modified mayo score range from 0 to 9; higher scores=more severe disease.	Up to Month 42
Number of Participants With Remission Based on Modified Partial Mayo Score at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42	Remission as per modified partial mayo score was defined as stool frequency subscore of 0 or 1, and rectal bleeding sub score of 0 at the specified time points. Modified partial mayo scores consisted of 2 components: stool frequency and rectal bleeding: each subscore graded from 0 to 3 with higher scores for each score = more severe disease. These scores were summed up to give a total modified partial mayo score range of 0 to 6; where higher scores indicating more severe disease.	Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42
Number of Participants With Remission Based on Total Mayo Score at Months 6, 18, 30 and 42	Remission as per total mayo score was defined by a total mayo score of 2 points or lower, with no individual subscore exceeding 1 point and a rectal bleeding subscore of 0. Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and physician global assessment (PGA), each subscore graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: participant's recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total mayo score range of 0 to 12, where higher scores indicating more severe disease.	Months 6, 18, 30 and 42
Number of Participants With Remission Based on Partial Mayo Score at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42	Remission as per partial mayo score was defined as partial mayo score of 2 points or lower, with no individual subscore exceeding 1 point and a rectal bleeding subscore of 0. Partial mayo score was an instrument designed to measure disease activity of UC without endoscopy. It consisted of 3 subscores: stool frequency, rectal bleeding and PGA with each subscore graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: participant's recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total partial mayo score range from 0 (normal or inactive disease) to 9 (severe disease) with higher scores indicating more severe disease.	Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42
Number of Participants With Remission Based on Modified Mayo Score at Months 18, 30 and 42	Remission as per modified mayo score was defined as an endoscopic subscore of 0 or 1, stool frequency subscore of 0 or 1, and rectal bleeding subscore of 0. Modified mayo score consisted of 3 components: stool frequency subscore, rectal bleeding subscore and endoscopic subscore: higher scores for each score = more severe disease. These scores were summed up to give a total modified mayo score range of 0 to 9; where higher scores indicating more severe disease.	Months 18, 30 and 42
Change From Baseline in Modified Mayo Score at Month 6	Modified mayo score is an instrument designed to measure disease activity of UC. Modified mayo scores consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore, each subscore graded from 0 to 3 with higher scores indicating more severe disease. These individual scores were summed up to give a total modified mayo score range of 0 to 9, where higher scores indicated more severe disease.	Baseline, Month 6
Change From Baseline in Modified Mayo Score at Months 18, 30 and 42	Modified mayo score is an instrument designed to measure disease activity of UC. Modified mayo scores consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore, each subscore graded from 0 to 3 with higher scores indicating more severe disease. These individual scores were summed up to give a total modified mayo score range of 0 to 9, where higher scores indicated more severe disease.	Baseline, Months 18, 30 and 42
Change From Baseline in Modified Partial Mayo Score at Months 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42	Modified partial mayo scores consisted of 2 subscores: stool frequency and rectal bleeding with each subscore graded from 0 to 3 with higher scores indicating more severe disease. Individual subscores were summed up to give a total modified partial mayo score range from 0 (normal or inactive disease) to 6 (severe disease) with higher scores indicating more severe disease.	Baseline, Months 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42
Change From Baseline in Total Mayo Score at Month 6	Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and PGA, each sub score graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: participant's recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total mayo score range of 0 to 12, where higher scores indicating more severe disease.	Baseline, Month 6
Change From Baseline in Total Mayo Score at Months 18, 30 and 42	Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and PGA, each sub score graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: participant's recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total mayo score range of 0 to 12, where higher scores indicating more severe disease.	Baseline, Months 18, 30 and 42
Change From Baseline in Partial Mayo Score at Months 1, 3 and 6	Partial mayo score was an instrument designed to measure disease activity of UC without endoscopy. It consisted of 3 subscores: stool frequency, rectal bleeding and PGA with each subscore graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: participant's recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total partial mayo score range from 0 (normal or inactive disease) to 9 (severe disease) with higher scores indicating more severe disease.	Baseline, Months 1, 3 and 6
Change From Baseline in Partial Mayo Score at Months 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42	Partial mayo score was an instrument designed to measure disease activity of UC without endoscopy. It consisted of 3 subscores: stool frequency, rectal bleeding and PGA with each subscore graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: participant's recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total partial mayo score ranges from 0 (normal or inactive disease) to 9 (severe disease) with higher scores indicating more severe disease.	Baseline, Months 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42
Number of Participants With Mucosal Healing at Months 6, 18, 30 and 42	Mucosal healing in participants was defined as the mayo endoscopic subscore of 0 or 1. The Mayo endoscopic subscore consisted of the findings of centrally read flexible sigmoidoscopy, graded from 0 to 3 with higher scores indicated more severe disease.	Months 6, 18, 30 and 42
Number of Participants With Clinical Response Based on Mayo Score at Months 6, 18, 30 and 42	Clinical response was defined as a decrease from baseline in mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and PGA, each sub score graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: participant's recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a mayo score range of 0 to 12, where higher scores indicating more severe disease.	Months 6, 18, 30 and 42
Change From Baseline in Fecal Calprotectin at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42	Change from baseline in fecal calprotectin (in micrograms per gram [mcg/g]) was reported.	Baseline, Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42
Change From Baseline in High Sensitivity C-Reactive Protein (Hs-CRP) Level at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42	Change From baseline in hs-CRP level (in milligrams per liter [mg/L]) is reported.	Baseline, Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment or worsened during the treatment period relative to the pretreatment state. AEs included both serious and all non-serious adverse events (irrespective of frequency threshold used to report other AEs in safety section).	Baseline up to 43 months
Number of Participants With Serious Infections	Serious infections were defined as any infections (viral, bacterial, and fungal) requiring parenteral antimicrobial therapy, hospitalization for treatment, or meeting other criteria that require the infection to be classified as serious adverse event. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events.	Baseline up to 43 months
Number of Participants With Clinical Laboratory Abnormalities	Abnormality criteria: Hematology: hemoglobin(Hg): <0.8* lower limit of normal (LLN); hematocrit: <0.8*LLN; lymphocytes: <0.8* LLN; lymphocytes/leukocytes: <0.8*LLN; erythrocytes: <0.8*LLN; erythrocytes mean corpuscular volume: <0.9*LLN; erythrocytes mean corpuscular Hg: <0.9*LLN; reticulocytes, reticulocytes/erythrocytes:>1.5* upper limit of normal (ULN); neutrophils, neutrophils/leukocytes: >1.2*ULN; basophils/leukocytes, eosinophils, eosinophils/leukocytes, monocytes/leukocytes: >1.2*ULN; leukocyte esterase: >=1; Clinical chemistry: bicarbonate:<0.9*LLN, bilirubin: >1.5*ULN; indirect bilirubin: >1.5* ULN; aspartate aminotransferase(AT): >3.0*ULN; alanine AT: >3.0*ULN; gamma glutamyl transferase: >3.0* ULN; creatine kinase: >2.0*ULN; potassium: >1.1*ULN; blood urea nitrogen: >1.3*ULN; creatinine: >1.3*ULN; urate: >1.2*ULN; cholesterol: >1.3*ULN; HDL-cholesterol: <0.8* LLN; LDL-cholesterol: >1.2*ULN; triglycerides: >1.3*ULN; glucose: >1.5*ULN; and urine Hg >=1.	Baseline up to 27 months
Number of Participants With Clinically Significant Laboratory Abnormalities Leading to Study Treatment Discontinuation	Laboratory abnormalities leading to study treatment discontinuation: 2 sequential neutrophil counts <750 neutrophils per cubic millimeter (mm^3); 2 sequential lymphocyte counts <500 lymphocytes/mm^3; 2 sequential hemoglobin <8.0 grams per deciliter; 2 sequential platelet counts <75000 platelets/mm^3; 2 sequential AST or ALT elevations >=3*ULN with at least one total bilirubin value >=2*ULN; 2 sequential AST or ALT elevations >=3*ULN accompanied by signs or symptoms consistent with hepatic injury; 2 sequential AST or ALT elevations >=5*ULN; 2 sequential increases in creatinine >50% and >0.5 milligrams per deciliter over A3921139 baseline; 2 sequential CK elevations >10*ULN unless the causality is known not to be medically serious (eg, exercise induced).	Baseline up to 43 months
Number of Participants With Vital Sign Abnormalities	Vital signs abnormality criteria included: 1) a) diastolic blood pressure (DBP) of (less than) <50 millimeter of mercury (mmHg), b) change greater than equal to (>=) 20 mmHg increase, c) change >=20 mmHg decrease; 2) a) systolic blood pressure (SBP) of <90 mmHg, b) change >=30 mmHg increase, c) change >=30 mmHg decrease; 3) a) pulse rate value of <40 beats per minute (bpm), b) pulse rate >120 bpm. Only those categories in which at least 1 participant had data were reported.	Baseline up to 43 months
Number of Participants With Clinically Significant Physical Examinations Abnormalities	Physical examination included assessment of the weight, general appearance, eyes, mouth, lungs, heart, abdomen, musculoskeletal, extremities, skin and lymph nodes. Clinical significance was assessed by the Investigator.	Baseline up to 43 months
Number of Participants With Opportunistic Infections, All Malignancy, Gastrointestinal Perforation and Cardiovascular Events Adjudicated by Adjudication Committee	Number of participants with adjudicated opportunistic infections including herpes zoster (non-adjacent or >2 adjacent dermatomes); all malignancies including non-melanoma skin cancer; gastrointestinal perforation and cardiovascular events including pulmonary embolism and cerebrovascular accident, adjudicated by adjudication committee were reported.	Baseline up to 43 months

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Winthrop KL, Vermeire S, Long MD, Panes J, Ng SC, Kulisek N, Mundayat R, Lawendy N, Vranic I, Modesto I, Su C, Melmed GY. Long-term Risk of Herpes Zoster Infection in Patients With Ulcerative Colitis Receiving Tofacitinib. Inflamm Bowel Dis. 2023 Jan 5;29(1):85-96. doi: 10.1093/ibd/izac063.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2017
• Primary Completion (Actual): February 14, 2020
• Study Completion (Actual): March 18, 2022

Study Registration Dates

• First Submitted: September 11, 2017
• First Submitted That Met QC Criteria: September 11, 2017
• First Posted (Actual): September 13, 2017

Study Record Updates

• Last Update Posted (Actual): March 21, 2023
• Last Update Submitted That Met QC Criteria: February 21, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: ulcerative colitis; inflammatory bowel disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tofacitinib
• Other Study ID Numbers: A3921288; RIVETING STUDY (Other Identifier: Alias Study Number); 2017-002274-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No