A multi-center parallel group study of tofacitinib in subjects with ulcerative colitis in stable remission

• Register: EUCTR
• Last refreshed on: 9 May 2022
• Main ID: EUCTR2017-002274-39-SK
• Date of registration: 27/10/2017
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc.
• Public title: A multi-center parallel group study of tofacitinib in subjects with ulcerative colitis in stable remission
• Scientific title: A PHASE 3B/4, MULTI-CENTER, DOUBLE-BLIND, RANDOMIZED, PARALLEL GROUP STUDY OF TOFACITINIB (CP-690,550) IN SUBJECTS WITH ULCERATIVE COLITIS IN STABLE REMISSION
• Date of first enrolment: 08/12/2017
• Target sample size: 130
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002274-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): yes

Countries of recruitment

Austria, Belgium, Canada, Czech Republic, Czechia, Germany, Hungary, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Poland, Russian Federation, Serbia, Slovakia, South Africa, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc.

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subjects currently enrolled in Study A3921139 who were initially assigned to tofacitinib 10 mg BID for a minimum of 2 consecutive years in Study A3921139 prior to and including baseline of Study A3921288.
2. Subjects who are in stable remission on tofacitinib 10 mg BID for the 6 month period in Study A3921139 up to and including baseline of Study A3921288, defined as meeting all of the following criteria:
a. A partial Mayo score =2, with no individual subscore >1 and a rectal bleeding subscore of 0 at each study where data is available visit during the 6 month period in Study A3921139 prior to and including baseline of Study A3921288;
b. AND at least one assessment of remission based on Mayo score;
• If an endoscopy was not completed =6 months prior to baseline of Study A3921288, then an endoscopy performed in Study A3921139 with an endoscopic subscore of 0 or 1, will be required prior to randomization into Study A3921288.
• All available assessments based on Mayo score during this period must show remission.
c. AND subjects must not be receiving any corticosteroid therapy for their UC for at least 4-weeks prior to baseline.
3. Female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 28 days after the last dose of assigned treatment. Subjects in Canada who are women of childbearing potential and sexually active must use two contraceptive methods at the same time: one highly effective contraceptive method and one additional effective contraceptive method (see Protocol Section 4.4.4).
4. Female subjects of childbearing potential must have a negative urine pregnancy test prior to randomization.
5. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, bowel movement diary calls, and other study procedures.
6. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 127
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

Exclusion criteria:
1. Subjects who were initially assigned to tofacitinib 10 mg BID at baseline of Study A3921139 whose tofacitinib dose was reduced to 5 mg BID due to safety or efficacy.
2. Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical findings suggestive of Crohn’s disease.
3. Subjects who in the opinion of the investigator are likely to require surgery for UC during the study period.
4. Subjects who are expected to receive any prohibited medications, including medications that are either moderate to potent CYP3A inducers or inhibitors, during the study period as specified in the protocol (see Protocol Appendix 3).
5. Subjects who are expected to receive live or attenuated virus vaccination during study period and for 6 weeks after last dose of investigational product.
6. Women who are pregnant or breastfeeding, or planning to become pregnant during the study period.
7. Subjects with evidence of colonic malignancy or any dysplasia (eg, “flat dysplasia”; polyp) identified on endoscopic exam during Study A3921139. Subjects with completely resected adenomatous polyp(s) outside of (proximal to) the extent of colitis may be eligible upon consultation with the sponsor. Note, pathology report must be reviewed prior to subject enrolment.
8. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
9. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study.
10. Subjects who, in the opinion of the investigator or Pfizer, will be uncooperative or unable to comply with study procedures.
11. Participation in other studies, excluding study A3921139, involving investigational drug(s) during study participation.
12. Subjects with any of the following risk factors for pulmonary embolism at baseline as defined by EMA`s PRAC (per Amendment 2 only):
- has heart failure
- has inherited coagulation disorders
- has had venous thromboembolism, either deep venous thrombosis or pulmonary embolism
- is taking combined hormonal contraceptives or hormone replacement therapy
- has malignany (association is strongest with cancers other than non-melanoma skin cancers)
- is undergoing major surgery.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Ulcerative colitis
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Intervention(s)

Trade Name: XELJANZ
Product Name: Tofacitinib citrate
Product Code: CP-690,550-10
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: tofacitinib
CAS Number: 540737-29-9
Current Sponsor code: CP-690,550-10
Other descriptive name: CP-690,550
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: The primary analysis will be performed at Month 6 based on the FAS for the estimation of treatment difference between two dose groups: Tofacitinib 10 mg BID and Tofacitinib 5 mg BID.
The stratified estimation of the treatment difference between tofacitinib 10 mg BID and 5 mg BID in the proportion of subjects with remission at Month 6 will be presented along with its 95% confidence interval (CI). The Cochran-Mantel-Haenszel (CMH) weight method will be used for the stratified estimation of the treatment difference. The stratified CI will be constructed using the NewCombe method. Subjects with dose escalation prior to Month 6 or with missing values at Month 6 will be treated as non-responders at Month 6.

Primary end point(s): Remission based on modified Mayo score at Month 6.

Main Objective: To evaluate the efficacy and safety of tofacitinib in subjects in stable remission on 10 mg BID who decrease the dose to and remain on 5 mg BID (“fixed 5 mg BID dose group”) compared to subjects remaining on 10 mg BID.

Secondary Objective: • To evaluate the efficacy and safety of tofacitinib in subjects in stable remission on 10 mg BID who decrease the dose to 5 mg BID with option for dose escalation for flare (“flexible dosing regimen”) compared to subjects staying on 10 mg BID.
• To evaluate the efficacy and safety of the subset of subjects in stable remission on 10 mg BID who have flare after dose decrease to tofacitinib 5 mg BID and are re-treated with 10 mg BID.

Secondary Outcome(s)

Secondary end point(s): Secondary Efficacy Endpoints:
• Time to loss of remission based on modified Mayo score.
• Remission at all applicable scheduled visits based on the following: modified Mayo score (excluding Month 6), modified partial Mayo score, total Mayo score, and partial Mayo score.
• Change from baseline (of Study A3921288) at all applicable scheduled visits in the following: modified Mayo score, modified partial Mayo score, total Mayo score, and partial Mayo score.
• Mucosal healing at all applicable scheduled visits.
• Clinical response based on Mayo score at all applicable scheduled visits.
• Change from baseline at all applicable scheduled visits in fecal calprotectin and hs-CRP levels.
For additional safety endpoints please refer to the study protocol.

Timepoint(s) of evaluation of this end point: For efficacy endpoints based on Mayo score, the change from baseline will be analyzed using an analysis of covariance model with treatment group, the endoscopic subscore at baseline (0 versus 1) as factors and baseline score as a covariate. For other endpoints, the change from baseline will be analyzed using linear mixed-effects model with baseline value, treatment group, the endoscopic subscore at baseline (0 versus 1), visit, and treatment group by visit interaction all as fixed effects, and an unstructured covariance matrix for within-subject measurements over visits. The adjusted estimations and associated 95% CI for the overall difference between the two groups will be computed.

Secondary ID(s)

A3921288

Source(s) of Monetary Support

Pfizer Inc.

Ethics review

Status: Approved
Approval date: 16/11/2017
Contact: