Long-Term Study Of CP-690,550 In Subjects With Ulcerative Colitis

Study Overview
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Brief Summary
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This study is an open label, long-term extension study for subjects with moderate to severe ulcerative colitis designed to evaluate long term therapy of CP-690,550.

Official Title
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A MULTI-CENTER, OPEN-LABEL STUDY OF CP-690,550 IN SUBJECTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: CP-690,550
* Drug: CP-690,550


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who completed induction studies A3921094 or A3921095 and were classified as not meeting clinical response criteria; OR Subjects who completed maintenance study A3921096 or who discontinued treatment early in Study A3921096 due to treatment failure. Exclusion Criteria: Subjects who had a major protocol violation in Study A3921094, A3921095 or A3921096. Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical findings suggestive of Crohn's disease. Subjects who have had surgery for ulcerative colitis or in the opinion of the investigator, are likely to require surgery for ulcerative colitis during the study period.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CP-690,550 5 mg BID<br>5 mg BID | Drug: CP-690,550<br>* 5 mg tablets, BID, for at least 12 months<br>|
| Experimental: CP-690,550 10 mg BID<br>10 mg BID | Drug: CP-690,550<br>* 10 mg tablets, BID, for at least 12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence Rates for Adjudicated Cardiovascular, Malignancy, Opportunistic Infections and Thromboembolic Safety Events | Incidence rates for adjudicated cardiovascular (major adverse cardiovascular event [MACE]), malignancy (non-melanoma skin cancer [NMSC], malignancies excluding NMSC, opportunistic infections (OIs) (both herpes zoster and non herpes zoster OIs) and thromboembolic (venous thromboembolism) safety events were analyzed. This outcome measure was measured in participants with events per 100 participants-years (pt with events/100 pts-yrs). | Baseline up to 28 days after last dose of study drug (up to 81 months for Tofacitinib 5 mg BID group and up to 85 months for Tofacitinib 10 mg BID group) | 
| 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 study drug 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. Treatment-emergent were events between first dose of study drug and up to 81 months for Tofacitinib 5 mg BID group and up to 85 months for Tofacitinib 10 mg BID group that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and all non-serious AEs. | Baseline up to 28 days after last dose of study drug (up to 81 months for Tofacitinib 5 mg BID group and up to 85 months for Tofacitinib 10 mg BID group) | 
| Number of Participants With Serious Infections as Treatment Emergent Adverse Events (TEAEs) | Serious infections were treated infections that required parenteral antimicrobial therapy or hospitalization for treatment or; met other criteria that required the infection to be classified as a serious adverse event (SAE). 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. Treatment-emergent were events between first dose of study drug and up to 81 months for Tofacitinib 5 mg BID group and up to 85 months for Tofacitinib 10 mg BID group that were absent before treatment or that worsened relative to pretreatment state. | Baseline up to 28 days after last dose of study drug (up to 81 months for Tofacitinib 5 mg BID group and up to 85 months for Tofacitinib 10 mg BID group) | 
| Number of Participants With Laboratory Test Abnormalities | Laboratory abnormalities: Hemoglobin, hematocrit, RBC: <0.8* LLN; reticulocytes (absolute [Abs], %): <0.5* LLN, >1.5* ULN; MCV, MCH: <0.9* LLN, >1.1* ULN; platelets:<0.5* LLN, >1.75* ULN; WBC:<0.6* LLN,>1.5* ULN; lymphocytes (Abs, %), total neutrophils (Abs,%):<0.8* LLN, >1.2* ULN; Basophils (Abs,%),eosinophils(Abs, %),monocytes(Abs, %):>1.2* ULN; total bilirubin,direct bilirubin,indirect bilirubin:>1.5* ULN; AST,ALT,gamma GT, LDH,ALP: >3.0* ULN; total protein,albumin: <0.8* LLN,>1.2* ULN: BUN,creatinine: >1.3* ULN;uric acid:>1.2* ULN; cholesterol,triglycerides: >1.3* ULN; cholesterol (HDL: <0.8* LLN; LDL: >1.2* ULN); sodium: <0.95* LLN, >1.05* ULN; potassium, chloride, calcium, bicarbonate: <0.9* LLN, >1.1* ULN; glucose: <0.6* LLN; creatine kinase >2.0* ULN; urine specific gravity: <1.003; urine pH: <4.5; urine (glucose,protein,blood,nitrite,leukocyte,esterase): >=1; Urine (RBC,WBC): >=20; urine epithelial cells:>=6; urine (casts,granular casts,hyaline casts): >1; urine bacteria:>20. | Baseline up to 28 days after last dose of study drug (up to 81 months for Tofacitinib 5 mg BID group and up to 85 months for Tofacitinib 10 mg BID group) | 
| Number of Participants With Vital Sign Abnormalities | Vital sign abnormalities included greater than or equal to (>=) 30 millimeter of mercury [mmHg] increase in systolic blood pressure (BP), >=30 mmHg decrease in systolic BP, Systolic BP (less than [<] 90 mmHg), >=20 mmHg increase in diastolic BP, >=20 mmHg decrease in diastolic BP, diastolic BP (<50 mmHg), pulse rate (<40 beats per minute [BPM]), pulse rate (greater than [>] 120 BPM). | Baseline up to 28 days after last dose of study drug (up to 81 months for Tofacitinib 5 mg BID group and up to 85 months for Tofacitinib 10 mg BID group) | 
| Number of Participants With Clinically Significant Changes in Physical Examinations From Baseline | Physical examinations included weight, general appearance, head, ears, eyes, nose, mouth, throat, thyroid, skin (presence of rash), lungs (auscultation), heart (auscultation for presence of murmurs, gallops, rubs, peripheral edema), abdominal (palpation and auscultation), perianal, musculoskeletal, extremities, neurologic (mental status, gait, reflexes, motor and sensory function, coordination) and lymph nodes. Clinically significant changes were judged by the investigator. | Baseline up to 28 days after last dose of study drug (up to 81 months for Tofacitinib 5 mg BID group and up to 85 months for Tofacitinib 10 mg BID group) | 
| Number of Participants With Electrocardiogram (ECG) Abnormalities | ECG abnormalities criteria: maximum PR interval (>=300 millisecond); maximum QRS complex (>=200 millisecond); and maximum QT interval (>=500 millisecond). | Baseline up to 28 days after last dose of study drug (up to 81 months for Tofacitinib 5 mg BID group and up to 85 months for Tofacitinib 10 mg BID group) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants in Partial Mayo Score (PMS) Remission at Months 1, 4, 6, 9, 15, 18, 21, 27, 30, 33, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81 and 84: Non-responder Imputation- Last Observation Carried Forward (NRI-LOCF) | PMS was an instrument designed to measure disease activity of UC without endoscopy. It consisted of 3 sub scores: stool frequency, rectal bleeding and PGA, each sub score graded from 0 to 3 with higher scores indicated higher disease severity. These sub scores were summed up to give a total PMS score range of 0 to 9, where higher score indicated more severe disease. PMS remission was defined as a partial Mayo score <=2 with no individual sub score >1. | Months 1, 4, 6, 9, 15, 18, 21, 27, 30, 33, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81 and 84 | 
| Number of Participants in Remission at Months 2, 12, 24 and 36: Observed Cases | Remission in participants was defined as a total Mayo score of less than or equals to (<=) 2, with no individual sub score exceeding 1 point and a rectal bleeding sub score of 0. Mayo score was an instrument designed to measure disease activity of ulcerative colitis (UC). It consisted of 4 sub scores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and physician global assessment (PGA), each sub score graded from 0 to 3 with higher scores indicated higher disease severity. These sub scores were summed up to give a total Mayo score range of 0 to 12, where higher score indicated more severe disease. | Months 2, 12, 24 and 36 | 
| Number of Participants in Remission at Months 2, 12, 24 and 36: Non-responder Imputation- Last Observation Carried Forward (NRI-LOCF) | Remission in participants was defined as a total Mayo score of <=2, with no individual sub score exceeding 1 point and a rectal bleeding sub score of 0. Mayo score was an instrument designed to measure disease activity of UC. It consisted of 4 sub scores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and PGA, each sub score graded from 0 to 3 with higher scores indicated higher disease severity. These sub scores were summed up to give a total Mayo score range of 0 to 12, where higher score indicated more severe disease. | Months 2, 12, 24 and 36 | 
| Number of Participants in Clinical Remission at Months 2, 12, 24 and 36: Observed Cases | Clinical remission in participants was defined as a total Mayo score of <=2 with no individual sub score exceeding 1 point. Mayo score was an instrument designed to measure disease activity of UC. It consisted of 4 sub scores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicated higher disease severity. These sub scores were summed up to give a total Mayo score range of 0 to 12, where higher score indicated more severe disease. | Months 2, 12, 24 and 36 | 
| Number of Participants in Clinical Remission at Months 2, 12, 24 and 36: Non-responder Imputation- Last Observation Carried Forward (NRI-LOCF) | Clinical remission in participants was defined as a total Mayo score of <=2 with no individual sub score exceeding 1 point. Mayo score was an instrument designed to measure disease activity of UC. It consisted of 4 sub scores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicated higher disease severity. These sub scores were summed up to give a total Mayo score range of 0 to 12, where higher score indicated more severe disease. | Months 2, 12, 24 and 36 | 
| Number of Participants in Partial Mayo Score (PMS) Remission at Months 1, 4, 6, 9, 15, 18, 21, 27, 30, 33, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81 and 84: Observed Cases | PMS was an instrument designed to measure disease activity of UC without endoscopy. It consisted of 3 sub scores: stool frequency, rectal bleeding and PGA, each sub score graded from 0 to 3 with higher scores indicated higher disease severity. These sub scores were summed up to give a total score range of 0 to 9, where higher score indicated more severe disease. PMS remission was defined as a partial Mayo score <=2 with no individual sub score >1. | Months 1, 4, 6, 9, 15, 18, 21, 27, 30, 33, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81 and 84 | 
| Number of Participants Who Achieved Mucosal Healing at Months 2, 12, 24 and 36: Observed Cases | Mucosal healing in participants was defined as Mayo endoscopic sub score of 0 or 1. The Mayo endoscopic sub score consisted of the findings of flexible sigmoidoscopy, graded from 0 to 3 with higher sub scores indicated higher disease severity. | Months 2, 12, 24 and 36 | 
| Number of Participants Who Achieved Mucosal Healing at Months 2, 12, 24 and 36: Non-responder Imputation- Last Observation Carried Forward (NRI-LOCF) | Mucosal healing in participants was defined as mayo endoscopic sub score of 0 or 1. The mayo endoscopic sub score consisted of the findings of flexible sigmoidoscopy, graded from 0 to 3 with higher sub scores indicating higher disease severity. | Months 2, 12, 24 and 36 | 
| Number of Participants With Total Inflammatory Bowel Disease Questionnaire (IBDQ) Score >=170 at Months 2, 6, 12, 18, 24, 30, 36, 48, 60, 72 and 84: Non-responder Imputation- Last Observation Carried Forward (NRI-LOCF) | IBDQ was a psychometrically validated patient reported outcome (PRO) instrument for measuring the disease-specific quality of life in participants with inflammatory bowel disease (IBD), including ulcerative colitis consisted of 32 items scored from 1 (worst response) to 7 (best response). For each domain, higher score indicates better quality of life (QOL). Total IBDQ score was the sum of each item score, and ranged from 32 to 224 with a higher score indicated better QOL. | Months 2, 6, 12, 18, 24, 30, 36, 48, 60, 72 and 84 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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long term treatment, Ulcerative colitis, open-label