Trial Outcomes & Findings for Tofacitinib For Treatment Of Chronic Pouchitis (NCT NCT04580277)

Last Updated: 2024-04-04

Results Overview

The proportion of subjects with clinical response at 8 weeks, defined as ≥2-point decrease in modified pouchitis disease activity index (mPDAI) with at least 1-point decrease in endoscopic subscore compared to the baseline.The mPDAI is a 0- 18 point scale of pouchitis disease severity, with higher scores corresponding to worse disease severity.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

6 participants

Primary outcome timeframe

8 weeks

Results posted on

2024-04-04

Participant Flow

Seven patients were screened and 6 met the eligibility criteria. One patient was ineligible due to an endoscopic PDAI subscore of 1 on screening pouchoscopy. Study recruitment was terminated prematurely due to COVID-19 pandemic-related recruitment challenges.

Participant milestones

Participant milestones
Measure	Chronic Active Pouchitis This arm included subjects with chronic active pouchitis who recieved tofactinib 10 mg twice daily for 8 weeks Tofacitinib 10 mg: Subjects in this arm will receive tofactinib 10 mg twice daily for 8 weeks
Overall Study STARTED	6
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Tofacitinib For Treatment Of Chronic Pouchitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Chronic Active Pouchitis n=6 Participants This arm included subjects with chronic active pouchitis who recieved tofactinib 10 mg twice daily for 8 weeks Tofacitinib 10 mg: Subjects in this arm will receive tofactinib 10 mg twice daily for 8 weeks
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	23.5 Years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants
Prior Biologic Use for Pouchitis	6 Participants n=5 Participants
Indication for Colectomy Active ulcerative colitis	6 Participants n=5 Participants
Indication for Colectomy Dysplasia/cancer	0 Participants n=5 Participants
Concomitant Medications On Antibiotics	4 Participants n=5 Participants
Concomitant Medications On Corticosteroids	1 Participants n=5 Participants
Concomitant Medications On Immunomodulators	0 Participants n=5 Participants
Concomitant Medications Other	1 Participants n=5 Participants
Extraintestinal Manifestations Arthritis	2 Participants n=5 Participants
Extraintestinal Manifestations Primary sclerosing cholangitis	1 Participants n=5 Participants
Extraintestinal Manifestations Other	0 Participants n=5 Participants
Extraintestinal Manifestations None	3 Participants n=5 Participants
Median Baseline mPDAI score	8.8 PDAI score n=5 Participants
Median Baseline Fecal Calprotectin	217 mcg/g n=5 Participants

PRIMARY outcome

Timeframe: 8 weeks

Outcome measures

Outcome measures
Measure	Chronic Active Pouchitis n=6 Participants This arm included subjects with chronic active pouchitis who recieved tofactinib 10 mg twice daily for 8 weeks Tofacitinib 10 mg: Subjects in this arm will receive tofactinib 10 mg twice daily for 8 weeks
Number of Participants With Clinical Response/Remission	4 Participants

SECONDARY outcome

Timeframe: 8 weeks

The proportion of subjects with clinical remission at 8 weeks, defined as modified pouchitis disease activity index (mPDAI) \<5.

Outcome measures

Outcome measures
Measure	Chronic Active Pouchitis n=6 Participants This arm included subjects with chronic active pouchitis who recieved tofactinib 10 mg twice daily for 8 weeks Tofacitinib 10 mg: Subjects in this arm will receive tofactinib 10 mg twice daily for 8 weeks
Number of Participants With Clinical Response	4 Participants

SECONDARY outcome

Timeframe: 8 weeks

The proportion of subjects with clinical remission at 8 weeks, defined as a modified pouch disease activity index (mPDAI) score of \<5 with a ≥2-point decrease from the baseline mPDAI score. The mPDAI is a 0- 18 point scale of pouchitis disease severity, with higher scores corresponding to worse disease severity.

Outcome measures

Outcome measures
Measure	Chronic Active Pouchitis n=6 Participants This arm included subjects with chronic active pouchitis who recieved tofactinib 10 mg twice daily for 8 weeks Tofacitinib 10 mg: Subjects in this arm will receive tofactinib 10 mg twice daily for 8 weeks
Number of Participants With Clinical Remission	3 Participants

SECONDARY outcome

Timeframe: 8 weeks

change in median mPDAI score at 8 weeks compared to baseline. The mPDAI (modified pouchitis disease activity index) is a 0- 18 point scale of pouchitis disease severity, with higher scores corresponding to worse disease severity.

Outcome measures

Outcome measures
Measure	Chronic Active Pouchitis n=6 Participants This arm included subjects with chronic active pouchitis who recieved tofactinib 10 mg twice daily for 8 weeks Tofacitinib 10 mg: Subjects in this arm will receive tofactinib 10 mg twice daily for 8 weeks
Change in mPDAI Score	-4.5 score on a scale Interval -8.33 to -4.34

SECONDARY outcome

Timeframe: 8 weeks

change in median clinical mPDAI sub-score at 8 weeks compared to baseline. The mPDAI (modified pouchitis disease activity index) is a 0- 18 point scale of pouchitis disease severity, with higher scores corresponding to worse disease severity.

Outcome measures

Outcome measures
Measure	Chronic Active Pouchitis n=6 Participants This arm included subjects with chronic active pouchitis who recieved tofactinib 10 mg twice daily for 8 weeks Tofacitinib 10 mg: Subjects in this arm will receive tofactinib 10 mg twice daily for 8 weeks
Change in mPDAI Clinical Sub-score	-1.7 score on a scale Interval -2.33 to -1.34

SECONDARY outcome

Timeframe: 8 weeks

change in median endoscopic mPDAI sub-score at 8 weeks compared to baseline. The mPDAI (modified pouchitis disease activity index) is a 0- 18 point scale of pouchitis disease severity, with higher scores corresponding to worse disease severity.

Outcome measures

Outcome measures
Measure	Chronic Active Pouchitis n=6 Participants This arm included subjects with chronic active pouchitis who recieved tofactinib 10 mg twice daily for 8 weeks Tofacitinib 10 mg: Subjects in this arm will receive tofactinib 10 mg twice daily for 8 weeks
Change in mPDAI Endoscopic Sub-score	-2 score on a scale Interval -6.0 to -1.0

SECONDARY outcome

Timeframe: 8 weeks

CGQL is a quality of life questionnaire used in inflammatory bowel diseases that incorporates three domains - quality of life, quality of health and energy level. Each domain is scored from 0 (worst) to 10 (best)and a total score is calculated by dividing the cumulative score by 30. The CGQL score can range from 0 to 1. Change in quality of life as measured by the Cleveland Global Quality of Life score (CGQL) at 8 weeks compared to baseline.

Outcome measures

Outcome measures
Measure	Chronic Active Pouchitis n=6 Participants This arm included subjects with chronic active pouchitis who recieved tofactinib 10 mg twice daily for 8 weeks Tofacitinib 10 mg: Subjects in this arm will receive tofactinib 10 mg twice daily for 8 weeks
Change in IBD-related Quality of Life	0.1 score on a scale Interval 0.0 to 0.3

Adverse Events

Chronic Pouchitis

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Chronic Pouchitis n=6 participants at risk This arm will include subjects with chronic pouchitis and will receive tofactinib 10 mg twice daily for 8 weeks Tofacitinib 10 mg: Subjects in this arm will receive tofactinib 10 mg twice daily for 8 weeks
Gastrointestinal disorders Sepsis	16.7% 1/6 • Number of events 1 • Adverse Events were monitored from the beginning of the study (week 0) up to 12 weeks (4 weeks after the completion of the study)
Gastrointestinal disorders Pouchitis Flare/SMA (superior mesentery artery) syndrome	16.7% 1/6 • Number of events 1 • Adverse Events were monitored from the beginning of the study (week 0) up to 12 weeks (4 weeks after the completion of the study)
Metabolism and nutrition disorders Severe Malnutrition/failure to thrive secondary to SMA syndrome	16.7% 1/6 • Number of events 1 • Adverse Events were monitored from the beginning of the study (week 0) up to 12 weeks (4 weeks after the completion of the study)
Gastrointestinal disorders worsening of superior mesenteric artery syndrome	16.7% 1/6 • Number of events 1 • Adverse Events were monitored from the beginning of the study (week 0) up to 12 weeks (4 weeks after the completion of the study)

Other adverse events

Other adverse events
Measure	Chronic Pouchitis n=6 participants at risk This arm will include subjects with chronic pouchitis and will receive tofactinib 10 mg twice daily for 8 weeks Tofacitinib 10 mg: Subjects in this arm will receive tofactinib 10 mg twice daily for 8 weeks
Gastrointestinal disorders Worsening of pouchitis disease symptoms	16.7% 1/6 • Number of events 1 • Adverse Events were monitored from the beginning of the study (week 0) up to 12 weeks (4 weeks after the completion of the study)
General disorders Flu-like symptom	16.7% 1/6 • Number of events 1 • Adverse Events were monitored from the beginning of the study (week 0) up to 12 weeks (4 weeks after the completion of the study)
General disorders COVID-19 test positive	16.7% 1/6 • Number of events 1 • Adverse Events were monitored from the beginning of the study (week 0) up to 12 weeks (4 weeks after the completion of the study)

Additional Information

Dr. Gil Y. Melmed

Cedars Sinai Inflammatory Bowel Disease Center

Phone: 310-423-4100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place