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low recruitment
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A phase 2 pilot study to evaluate the effectiveness of tofacitinib in subjects with chronic pouchitis
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Chronic pouchitis | Experimental | This arm will include subjects with chronic pouchitis and will receive tofactinib 10 mg twice daily for 8 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tofacitinib 10 mg | Drug | Subjects in this arm will receive tofactinib 10 mg twice daily for 8 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 8 weeks |
| Number of Participants With Clinical Remission |
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Inclusion Criteria:
Exclusion Criteria:
Subjects with IPAA surgery done for Crohn's disease (CD) or familial adenomatous polyposis (FAP) indications.
Subjects with primary CD of pouch, isolated or predominant cuffitis or mechanical complications of the ileal pouch.
Subjects with prior exposure to tofacitinib.
Subjects with a diverting stoma.
Subjects with a prior history or risk factors for venous thromboembolism.
Subjects with active bacterial, parasitic, fungal, mycobacterial, or viral infection.
Subjects with a history of latent or active tuberculosis.
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.
Female subjects who are pregnant or lactating.
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.
Subjects with clinically significant laboratory abnormalities at study screening.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cedars-Sinai Medical Center | Los Angeles | California | 90048 | United States |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Count of Participants | Participants | 8 weeks |
|
Adverse Events were monitored from the beginning of the study (week 0) up to 12 weeks (4 weeks after the completion of the study)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Chronic Pouchitis | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sepsis | Gastrointestinal disorders | Systematic Assessment | Patient hospitalized with sepsis related to shigella infection after starting tofacitinib. This patient recovered completely, resumed tofacitinib after a 6-day treatment interruption and completed the 8-week study. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Worsening of pouchitis disease symptoms | Gastrointestinal disorders | Systematic Assessment | Event was moderate in severity and unrelated to Investigational Drug. |
Limitations of this study included a single center design, small sample size, and absence of a control arm. This study also lacked long-term follow-up data to assess durability of response to tofacitinib and its long-term safety in chronic pouchitis. This study also only included patients with chronic pouchitis and its findings may not be applicable to other chronic inflammatory pouch disorders. Study recruitment was terminated prematurely due to COVID-19 pandemic-related recruitment challenges.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Gil Y. Melmed | Cedars Sinai Inflammatory Bowel Disease Center | 310-423-4100 | gil.melmed@cshs.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 2, 2022 | Feb 6, 2024 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D019449 | Pouchitis |
| ID | Term |
|---|---|
| D007079 | Ileitis |
| D004751 | Enteritis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
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| ID | Term |
|---|---|
| C479163 | tofacitinib |
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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.
| 8 weeks |
| 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. | 8 weeks |
| 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. | 8 weeks |
| 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. | 8 weeks |
| 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. | 8 weeks |
| Participants |
|
| Age, Continuous | Median | Full Range | Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Prior Biologic Use for Pouchitis | Count of Participants | Participants |
|
| Indication for Colectomy | Count of Participants | Participants |
|
| Concomitant Medications | Study subjects were allowed to remain on permitted concomitant medications provided the patient was on a stable dose for ≥2 weeks prior to starting tofactinib. Patients stayed on stable doses of these medications for the study duration of 8 weeks. | Count of Participants | Participants |
|
| Extraintestinal Manifestations | Count of Participants | Participants |
|
| Median Baseline mPDAI score | The modified PDAI (mPDAI), which can range from 0 to 12, is calculated from 2 separate 6-point scales assessing clinical symptoms and endoscopic findings. Patients are classified as either having pouchitis (PDAI score ≥5) or as not having pouchitis (PDAI score <5). Greater clinical scores and endoscopy scores correspond to worse disease severity." | Median | Full Range | PDAI score |
|
| Median Baseline Fecal Calprotectin | Median | Full Range | mcg/g |
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| Units |
|---|
| Counts |
|---|
| 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. | Posted | Count of Participants | Participants | 8 weeks |
|
|
|
| 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. | Posted | Count of Participants | Participants | 8 weeks |
|
|
|
| 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. | Posted | Median | Inter-Quartile Range | score on a scale | 8 weeks |
|
|
|
| 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. | Posted | Median | Inter-Quartile Range | score on a scale | 8 weeks |
|
|
|
| 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. | Posted | Median | Inter-Quartile Range | score on a scale | 8 weeks |
|
|
|
| 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. | Posted | Median | Inter-Quartile Range | score on a scale | 8 weeks |
|
|
|
| 0 |
| 6 |
| 1 |
| 6 |
| 1 |
| 6 |
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| Pouchitis Flare/SMA (superior mesentery artery) syndrome | Gastrointestinal disorders | Systematic Assessment | Event was unrelated to Investigational Drug. Participant recovered without sequelae. |
|
| Severe Malnutrition/failure to thrive secondary to SMA syndrome | Metabolism and nutrition disorders | Systematic Assessment | Event was unrelated to Investigational Drug and participant recovered without sequelae. |
|
| worsening of superior mesenteric artery syndrome | Gastrointestinal disorders | Systematic Assessment | Event outcome is ongoing and unrelated to Investigational Drug. |
|
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| Flu-like symptom | General disorders | Systematic Assessment | Event was mild in severity and unrelated to Investigational Drug. Participant recovered without sequelae. |
|
| COVID-19 test positive | General disorders | Systematic Assessment | Event was mild in severity and unrelated to Investigational Drug. Patient recovered without sequelae. |
|
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| D004066 |
| Digestive System Diseases |
| D007410 | Intestinal Diseases |
| D007077 | Ileal Diseases |