NCT03281304

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

Terminated Phase 4 Results posted Last updated 21 March 2023

What this trial tests

Phase 4 trial testing CP-690,500 5 mg in Ulcerative Colitis in 140 participants. Terminated before completion.

Timeline

16 November 2017

Primary endpoint
14 February 2020

18 March 2022

Quick facts

Lead sponsor	Pfizer
Phase	Phase 4
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	140
Start date	16 November 2017
Primary completion	14 February 2020
Estimated completion	18 March 2022
Sites	80 locations across Italy, Japan, Poland, South Korea, New Zealand, Netherlands, Russia, Belgium

Drugs / interventions tested

• CP-690,500 5 mg — full drug profile →
• CP-690,550 10 mg — full drug profile →

Conditions studied

• Ulcerative Colitis — all drugs for Ulcerative Colitis →

Sponsor

Pfizer — full company profile →

Who can join

18 and older, any sex, with Ulcerative Colitis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Remission Based on Modified Mayo Score at Month 6 Primary · 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.

Group	Value	95% CI
Tofacitinib 5 mg BID	54
Tofacitinib 10 mg BID	63

Time to Loss of Remission Based on Modified Mayo Score Using Kaplan-Meier Method Secondary · Up to Month 42

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 compo

Group	Value	95% CI
Tofacitinib 5 mg BID	NA	29 – 1268
Tofacitinib 10 mg BID	1270	28 – 1270

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 Secondary · 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.

Month 1

Group	Value	95% CI
Tofacitinib 5 mg BID	62
Tofacitinib 10 mg BID	64

Month 3

Group	Value	95% CI
Tofacitinib 5 mg BID	57
Tofacitinib 10 mg BID	65

Month 6

Group	Value	95% CI
Tofacitinib 5 mg BID	57
Tofacitinib 10 mg BID	67

Month 9

Group	Value	95% CI
Tofacitinib 5 mg BID	52
Tofacitinib 10 mg BID	66

Month 12

Group	Value	95% CI
Tofacitinib 5 mg BID	50
Tofacitinib 10 mg BID	61

Month 15

Group	Value	95% CI
Tofacitinib 5 mg BID	48
Tofacitinib 10 mg BID	58

Month 18

Group	Value	95% CI
Tofacitinib 5 mg BID	45
Tofacitinib 10 mg BID	55

Month 21

Group	Value	95% CI
Tofacitinib 5 mg BID	46
Tofacitinib 10 mg BID	51

Number of Participants With Remission Based on Total Mayo Score at Months 6, 18, 30 and 42 Secondary · 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

Month 6

Group	Value	95% CI
Tofacitinib 5 mg BID	53
Tofacitinib 10 mg BID	61

Month 18

Group	Value	95% CI
Tofacitinib 5 mg BID	33
Tofacitinib 10 mg BID	47

Month 30

Group	Value	95% CI
Tofacitinib 5 mg BID	35
Tofacitinib 10 mg BID	44

Month 42

Group	Value	95% CI
Tofacitinib 5 mg BID	22
Tofacitinib 10 mg BID	24

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 Secondary · 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 performanc

Month 1

Group	Value	95% CI
Tofacitinib 5 mg BID	62
Tofacitinib 10 mg BID	64

Month 3

Group	Value	95% CI
Tofacitinib 5 mg BID	57
Tofacitinib 10 mg BID	65

Month 6

Group	Value	95% CI
Tofacitinib 5 mg BID	56
Tofacitinib 10 mg BID	66

Month 9

Group	Value	95% CI
Tofacitinib 5 mg BID	52
Tofacitinib 10 mg BID	66

Month 12

Group	Value	95% CI
Tofacitinib 5 mg BID	50
Tofacitinib 10 mg BID	61

Month 15

Group	Value	95% CI
Tofacitinib 5 mg BID	48
Tofacitinib 10 mg BID	58

Month 18

Group	Value	95% CI
Tofacitinib 5 mg BID	44
Tofacitinib 10 mg BID	55

Month 21

Group	Value	95% CI
Tofacitinib 5 mg BID	46
Tofacitinib 10 mg BID	50

Number of Participants With Remission Based on Modified Mayo Score at Months 18, 30 and 42 Secondary · 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.

Month 18

Group	Value	95% CI
Tofacitinib 5 mg BID	37
Tofacitinib 10 mg BID	48

Month 30

Group	Value	95% CI
Tofacitinib 5 mg BID	35
Tofacitinib 10 mg BID	44

Month 42

Group	Value	95% CI
Tofacitinib 5 mg BID	23
Tofacitinib 10 mg BID	24

Change From Baseline in Modified Mayo Score at Month 6 Secondary · Baseline, 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.

Group	Value	95% CI
Tofacitinib 5 mg BID	0.6	± 0.2
Tofacitinib 10 mg BID	0.3	± 0.2

Change From Baseline in Modified Mayo Score at Months 18, 30 and 42 Secondary · Baseline, 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.

Change at Month 18

Group	Value	95% CI
Tofacitinib 5 mg BID	0.5	± 1.3
Tofacitinib 10 mg BID	0.3	± 1.5

Change at Month 30

Group	Value	95% CI
Tofacitinib 5 mg BID	0.3	± 1.2
Tofacitinib 10 mg BID	0.1	± 0.9

Change at Month 42

Group	Value	95% CI
Tofacitinib 5 mg BID	0.3	± 0.9
Tofacitinib 10 mg BID	0.2	± 1.1

Change From Baseline in Modified Partial Mayo Score at Months 1, 3 and 6 Secondary · Baseline, 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.

Change at Month 1

Group	Value	95% CI
Tofacitinib 5 mg BID	0.1	± 0.1
Tofacitinib 10 mg BID	0.2	± 0.1

Change at Month 3

Group	Value	95% CI
Tofacitinib 5 mg BID	0.2	± 0.1
Tofacitinib 10 mg BID	0.1	± 0.1

Change at Month 6

Group	Value	95% CI
Tofacitinib 5 mg BID	0.1	± 0.1
Tofacitinib 10 mg BID	0.2	± 0.1

Change From Baseline in Modified Partial Mayo Score at Months 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42 Secondary · Baseline, 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.

Change at Month 9

Group	Value	95% CI
Tofacitinib 5 mg BID	0.1	± 0.7
Tofacitinib 10 mg BID	0.1	± 0.6

Change at Month 12

Group	Value	95% CI
Tofacitinib 5 mg BID	0.1	± 0.5
Tofacitinib 10 mg BID	0.1	± 0.7

Change at Month 15

Group	Value	95% CI
Tofacitinib 5 mg BID	0.2	± 0.8
Tofacitinib 10 mg BID	0.1	± 0.6

Change at Month 18

Group	Value	95% CI
Tofacitinib 5 mg BID	0.1	± 0.6
Tofacitinib 10 mg BID	0.1	± 0.8

Change at Month 21

Group	Value	95% CI
Tofacitinib 5 mg BID	0.1	± 0.5
Tofacitinib 10 mg BID	0.2	± 1.1

Change at Month 24

Group	Value	95% CI
Tofacitinib 5 mg BID	0.0	± 0.5
Tofacitinib 10 mg BID	0.0	± 0.6

Change at Month 27

Group	Value	95% CI
Tofacitinib 5 mg BID	0.1	± 0.5
Tofacitinib 10 mg BID	0.1	± 0.7

Change at Month 30

Group	Value	95% CI
Tofacitinib 5 mg BID	0.1	± 0.7
Tofacitinib 10 mg BID	0.0	± 0.6

Change From Baseline in Total Mayo Score at Month 6 Secondary · Baseline, 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.

Group	Value	95% CI
Tofacitinib 5 mg BID	0.9	± 0.2
Tofacitinib 10 mg BID	0.4	± 0.3

Change From Baseline in Total Mayo Score at Months 18, 30 and 42 Secondary · Baseline, 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.

Change at Month 18

Group	Value	95% CI
Tofacitinib 5 mg BID	0.7	± 1.7
Tofacitinib 10 mg BID	0.4	± 1.9

Change at Month 30

Group	Value	95% CI
Tofacitinib 5 mg BID	0.4	± 1.4
Tofacitinib 10 mg BID	0.1	± 1.2

Change at Month 42

Group	Value	95% CI
Tofacitinib 5 mg BID	0.4	± 1.2
Tofacitinib 10 mg BID	0.2	± 1.4

Adverse events — posted to ClinicalTrials.gov

Time frame: From baseline up to 4 weeks after last dose (maximum up to 43 months). Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Tofacitinib 5 mg BID

Serious: 7/70 (10%)

Deaths: 0/70

Tofacitinib 10 mg BID

Serious: 16/70 (23%)

Deaths: 1/70

Serious adverse events (24 terms)

Reaction	System	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
COVID-19	Infections and infestations	—	—
COVID-19 pneumonia	Infections and infestations	—	—
Angina pectoris	Cardiac disorders	—	—
Cellulitis	Infections and infestations	—	—
Urinary tract infection	Infections and infestations	—	—
Limb injury	Injury, poisoning and procedural complications	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Squamous cell carcinoma of the vulva	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Cerebrovascular accident	Nervous system disorders	—	—
Breast disorder	Reproductive system and breast disorders	—	—
Endometrial hyperplasia	Reproductive system and breast disorders	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—
Colon dysplasia	Gastrointestinal disorders	—	—
Haemorrhoids	Gastrointestinal disorders	—	—
Large intestine polyp	Gastrointestinal disorders	—	—
Pancreatitis	Gastrointestinal disorders	—	—
Appendicitis	Infections and infestations	—	—
Herpes zoster oticus	Infections and infestations	—	—
Pneumonia	Infections and infestations	—	—
Ankle fracture	Injury, poisoning and procedural complications	—	—
Spinal stenosis	Musculoskeletal and connective tissue disorders	—	—
Adenocarcinoma of colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Diffuse large B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—

Other adverse events (49 terms — click to expand)

Reaction	System	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID
Colitis ulcerative	Gastrointestinal disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
SARS-CoV-2 test positive	Investigations	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Bronchitis	Infections and infestations	—	—
Herpes zoster	Infections and infestations	—	—
Oral herpes	Infections and infestations	—	—
Blood creatine phosphokinase increased	Investigations	—	—
Hypertension	Vascular disorders	—	—
Lymphopenia	Blood and lymphatic system disorders	—	—
Pyrexia	General disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—
Headache	Nervous system disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Large intestine polyp	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Influenza	Infections and infestations	—	—
Aspartate aminotransferase increased	Investigations	—	—
Faecal calprotectin increased	Investigations	—	—
Lymphocyte count decreased	Investigations	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Rectal haemorrhage	Gastrointestinal disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Oedema peripheral	General disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—
Haemorrhoids	Gastrointestinal disorders	—	—
Mouth ulceration	Gastrointestinal disorders	—	—
Chest pain	General disorders	—	—
Fatigue	General disorders	—	—
COVID-19	Infections and infestations	—	—
Clostridium difficile infection	Infections and infestations	—	—
Sinusitis	Infections and infestations	—	—
Urinary tract infection	Infections and infestations	—	—
Hypercholesterolaemia	Metabolism and nutrition disorders	—	—
Arthritis	Musculoskeletal and connective tissue disorders	—	—

Most-reported serious reactions: COVID-19, COVID-19 pneumonia, Angina pectoris, Cellulitis, Urinary tract infection, Limb injury, Back pain, Squamous cell carcinoma of the vulva.

Data from ClinicalTrials.gov NCT03281304 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. A Comprehensive Overview of Globally Approved JAK Inhibitors.
   Shawky AM, Almalki FA, Abdalla AN, Abdelazeem AH, et al · · 2022 · cited 222× · PMID 35631587 · DOI 10.3390/pharmaceutics14051001
2. Immunology of Inflammatory Bowel Disease: Molecular Mechanisms and Therapeutics.
   Lu Q, Yang MF, Liang YJ, Xu J, et al · · 2022 · cited 152× · PMID 35310454 · DOI 10.2147/jir.s353038
3. Safety and efficacy of tofacitinib for treatment of ulcerative colitis: final analysis of OCTAVE Open, an open-label, long-term extension study with up to 7.0 years of treatment.
   Sandborn WJ, Lawendy N, Danese S, Su C, et al · · 2022 · cited 113× · PMID 34854095 · DOI 10.1111/apt.16712
4. STAT proteins: a kaleidoscope of canonical and non-canonical functions in immunity and cancer.
   Awasthi N, Liongue C, Ward AC. · · 2021 · cited 97× · PMID 34809691 · DOI 10.1186/s13045-021-01214-y
5. JAK inhibitors: A new dawn for oral therapies in inflammatory bowel diseases.
   Herrera-deGuise C, Serra-Ruiz X, Lastiri E, Borruel N. · · 2023 · cited 65× · PMID 36936239 · DOI 10.3389/fmed.2023.1089099
6. Tofacitinib for the Treatment of Ulcerative Colitis: An Integrated Summary of up to 7.8 Years of Safety Data from the Global Clinical Programme.
   Sandborn WJ, D'Haens GR, Sands BE, Panaccione R, et al · · 2023 · cited 57× · PMID 36124702 · DOI 10.1093/ecco-jcc/jjac141
7. Outcomes of Tofacitinib Dose Reduction in Patients with Ulcerative Colitis in Stable Remission from the Randomised RIVETING Trial.
   Vermeire S, Su C, Lawendy N, Kobayashi T, et al · · 2021 · cited 46× · PMID 33290538 · DOI 10.1093/ecco-jcc/jjaa249
8. Efficacy, Safety and Future Perspectives of JAK Inhibitors in the IBD Treatment.
   Dudek P, Fabisiak A, Zatorski H, Malecka-Wojciesko E, et al · · 2021 · cited 33× · PMID 34884361 · DOI 10.3390/jcm10235660