Ileal Pouch, Ileal Pouchitis, Pouchitis
Conditions
Keywords
chronic pouchitis, tofacitinib, antibiotic-refractory pouchitis, antibiotic-dependent pouchitis
Brief summary
A phase 2 pilot study to evaluate the effectiveness of tofacitinib in subjects with chronic pouchitis
Detailed description
The proposed study is a phase 2, open-label study of tofactinib in treatment of patients with chronic pouchitis. Subjects with chronic active pouchitis will be screened and recruited if they meet eligibility criteria. Eligible subjects will undergo baseline clinical evaluation, laboratory testing and a pouch endoscopy. They will then receive oral tofacitinib 10 mg twice daily for 8 weeks. Clinical and laboratory data will be collected at week 4 and week 8, and all subjects will undergo a end of treatment pouch endoscopy at 8 weeks. Clinical, laboratory and endoscopic data at 8 weeks will be compared to the baseline data to evaluate study outcomes.
Interventions
Subjects in this arm will receive tofactinib 10 mg twice daily for 8 weeks
Sponsors
Cedars-Sinai Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects ages 18 to 80 2. Subjects with a history of proctocolectomy with ileal pouch anal anastomosis (IPAA) for UC at least 6 months prior to screening. 3. Subjects with pouchitis that is chronic, defined by a mPDAI score ≥5 assessed as the average from 3 days immediately prior to the baseline study visit and a minimum endoscopic sub-score of 2 (outside the staple or suture line) with either (a) ≥ 3 recurrent episodes within 1 year prior to the screening treated with ≥2 weeks of antibiotic or other prescription therapy, (b) requiring maintenance antibiotic therapy taken continuously for ≥4 weeks immediately prior to the baseline study visit 4. Women of childbearing potential must have documentation of a negative pregnancy test at screening and must agree to use two highly effective methods of birth control during the study and for at least 1 month after completion of study drug dosing.
Exclusion criteria
1. Subjects with IPAA surgery done for Crohn's disease (CD) or familial adenomatous polyposis (FAP) indications. 2. Subjects with primary CD of pouch, isolated or predominant cuffitis or mechanical complications of the ileal pouch. 3. Subjects with prior exposure to tofacitinib. 4. Subjects with a diverting stoma. 5. Subjects with a prior history or risk factors for venous thromboembolism. 6. Subjects with active bacterial, parasitic, fungal, mycobacterial, or viral infection. 7. Subjects with a history of latent or active tuberculosis. 8. Subjects positive for hepatitis B virus (HBV) surface antigen, hepatitis B virus core antibody with a negative hepatitis B surface antibody or with detectable serum hepatitis B DNA. 9. Female subjects who are pregnant or lactating. 10. Female subjects of childbearing potential who are sexually active and do not agree to using two highly effective methods of contraception during the study period. 11. Subjects with clinically significant laboratory abnormalities at study screening. * Other eligibility criteria apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Response/Remission | 8 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Remission | 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. |
| Change in mPDAI Score | 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. |
| Number of Participants With Clinical Response | 8 weeks | The proportion of subjects with clinical remission at 8 weeks, defined as modified pouchitis disease activity index (mPDAI) \<5. |
| Change in mPDAI Endoscopic Sub-score | 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. |
| Change in IBD-related Quality of Life | 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. |
| Change in mPDAI Clinical Sub-score | 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. |
Countries
United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Chronic Active Pouchitis |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 23.5 Years |
| Concomitant Medications On Antibiotics | 4 Participants |
| Concomitant Medications On Corticosteroids | 1 Participants |
| Concomitant Medications On Immunomodulators | 0 Participants |
| Concomitant Medications Other | 1 Participants |
| Extraintestinal Manifestations Arthritis | 2 Participants |
| Extraintestinal Manifestations None | 3 Participants |
| Extraintestinal Manifestations Other | 0 Participants |
| Extraintestinal Manifestations Primary sclerosing cholangitis | 1 Participants |
| Indication for Colectomy Active ulcerative colitis | 6 Participants |
| Indication for Colectomy Dysplasia/cancer | 0 Participants |
| Median Baseline Fecal Calprotectin | 217 mcg/g |
| Median Baseline mPDAI score | 8.8 PDAI score |
| Prior Biologic Use for Pouchitis | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 1 / 6 |
| serious Total, serious adverse events | 1 / 6 |
Outcome results
Primary
Number of Participants With Clinical Response/Remission
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.
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chronic Active Pouchitis | Number of Participants With Clinical Response/Remission | 4 Participants |
Secondary
Change in IBD-related Quality of Life
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.
Time frame: 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chronic Active Pouchitis | Change in IBD-related Quality of Life | 0.1 score on a scale |
Secondary
Change in mPDAI Clinical Sub-score
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.
Time frame: 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chronic Active Pouchitis | Change in mPDAI Clinical Sub-score | -1.7 score on a scale |
Secondary
Change in mPDAI Endoscopic Sub-score
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.
Time frame: 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chronic Active Pouchitis | Change in mPDAI Endoscopic Sub-score | -2 score on a scale |
Secondary
Change in mPDAI Score
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.
Time frame: 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chronic Active Pouchitis | Change in mPDAI Score | -4.5 score on a scale |
Secondary
Number of Participants With Clinical Remission
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.
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chronic Active Pouchitis | Number of Participants With Clinical Remission | 3 Participants |
Secondary
Number of Participants With Clinical Response
The proportion of subjects with clinical remission at 8 weeks, defined as modified pouchitis disease activity index (mPDAI) \<5.
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chronic Active Pouchitis | Number of Participants With Clinical Response | 4 Participants |