A study to investigate the efficacy of CP-690,550 in subjects with moderate to severe ulcerative colitis.

• Register: EUCTR
• Last refreshed on: 4 August 2015
• Main ID: EUCTR2011-004578-27-LV
• Date of registration: 01/03/2012
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc, 235 East 42nd Street, New York, New York 10017
• Public title: A study to investigate the efficacy of CP-690,550 in subjects with moderate to severe ulcerative colitis.
• Scientific title: A MULTICENTRE, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY OF ORAL CP-690,550 AS AN INDUCTION THERAPY IN SUBJECTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS
• Date of first enrolment: 23/05/2012
• Target sample size: 545
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-004578-27
• 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

Countries of recruitment

Australia, Austria, Belgium, Brazil, Canada, Colombia, Croatia, Czech Republic, Denmark, Estonia, France, Germany, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Latvia, Netherlands, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Taiwan, 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. Subject must be at least 18 years of age
2. Males and females with a diagnosis (endoscopic or radiographic and histological) of UC >4 months prior to entry into the study. A biopsy report supporting the diagnosis prior to the baseline visit must be available in the source documents.
3. Subjects with moderately to severely active UC as defined by a total Mayo score of >6, with a rectal bleeding score of >1 and an endoscopic subscore of >2 on the Mayo score determined within 10 days of baseline visit (Visit 2).
4. Subjects must have failed or be intolerant (discontinued the medication due to an
adverse event as determined by the investigator) of at least one of the following treatments for UC:
- Oral or intravenous corticosteroids.
- Azathioprine or 6-mercaptopurine (6-MP).
- Anti-TNF-alpha therapy: infliximab or adalimumab.
5. Subjects currently receiving the following treatment for UC are eligible providing they have been and are anticipated to be on stable dose for designated period of time:
- Oral 5-ASA or sulfasalazine stable dose for at least 4 weeks prior to baseline and during the study period.
- Oral corticosteroids (prednisone equivalent up to 25 mg/day; budesonide up to 9 mg/day) stable dose for at least 2 weeks prior to baseline and during the study period.
- Chronic treatment for UC with antibiotics (eg, metronidazole, rifaximin) stable dose for at least 2 weeks prior to baseline and during the study period.
6. No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB) prior to randomization as defined by all of the following:
- A negative QuantiFERON-TB Gold (QFT-G) In-Tube test documented within 3 months prior to or during screening. If initial and repeat QFT-G
tests are indeterminate, a negative Mantoux/Purified Protein Derivative (PPD) tuberculin skin test(with a result of <5 mm of induration) documented within 3 months prior to or during screening is required. [Subjects with
a history of Bacille Calmette Guérin (BCG) vaccination must have a negative QFT-G test].
- A chest radiograph, taken within the 3 months prior to or during screening, without changes suggestive of active TB infection as determined by a qualified radiologist.
- No history of either untreated or inadequately treated latent or active TB infection.
- If a subject has previously received an adequate course of therapy for either latent (9 months of isoniazid in a locale where rates of primary multi-drug TB resistance are <5% or an acceptable alternative regimen) or active (acceptable multi-drug regimen) TB infection, neither a QFT-G test nor a PPD test is needed, but a chest radiograph must still be obtained if not performed within 3 months prior to a given Screening visit. Documentation of adequate treatment for TB will be obtained prior to first dose of study drug.
- A subject who is currently being treated for active TB infection is to be excluded.
- A subject who is currently being treated for latent TB infection can only be enrolled with confirmation of current incidence rates of multi-drug resistant TB infection in the locale, documentation of an adequate treatment regimen, and with prior approval by the sponsor.
7. Female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 4 weeks after the last dose of assigned treatment.
8. Women of childbearing potential must have a negative pregnancy test prior
Exclusion criteria:
1. Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical findings suggestive of Crohn’s disease.
2. Subjects with disease limited to distal 15 cm.
3. Subjects without previous treatment for UC (ie, treatment-naïve).
4. Subjects receiving the following therapy within the designated time period or are expected to receive any of these therapies during the study period:
- Azathioprine, 6-mercaptopurine, or methotrexate within 2 weeks prior to baseline.
- Anti-TNF-alpha therapy (eg, infliximab, adalimumab, or certolizumab) within 8 weeks prior to baseline.
- Cyclosporine, mycophenolate mofetil/mycophenolic acid, or tacrolimus within 4 weeks prior to baseline.
- Interferon therapy within 8 weeks prior to baseline.
- Intravenous corticosteroids within 2 weeks prior to baseline.
- Rectally administered formulation of corticosteroids or 5-ASA within 2 weeks prior to baseline.
- Anti-adhesion molecule therapy taken within 1 year (eg, natalizumab or any investigational anti-adhesion molecule therapy).
Subjects with prior treatment with lymphocyte-depleting agents/ Subjects who have received rituximab or other selective B lymphocyte depleting agents are eligible if they have not received such therapy for at least 1 year prior to baseline.
- Other marketed immunosuppressants or biologics with immunomodulatory properties within 3 months prior to baseline.
5. Subjects displaying clinical signs of fulminant colitis or toxic megacolon.
6. Subjects with evidence of colonic adenomas or dysplasia. However, subjects with prior history of adenomatous polyps will be eligible if the polyps have been completely removed and the subjects are free of polyps at baseline.
7. Subjects at risk for colorectal cancer must have a colonoscopy. Colonoscopy report and pathology report (if biopsies are obtained) must be available in the source document:
- If the subject is >50 years of age, a colonoscopy within 10 years of the screening visit is required to exclude adenomatous polyps. Subjects whose adenomas have been completely excised at baseline will be eligible.
- If the subject has extensive colitis for >8 years or disease limited to left side of colon (ie, distal to splenic flexure) for >10 years, regardless of age, a colonoscopy within 1 year of the screening visit is required to survey for dysplasia. Subjects with dysplasia or cancer identified on biopsies will be excluded.
8. Subjects who have had surgery for UC or in the opinion of the Investigator, are likely to require surgery for UC during the study period
9. Subjects who have positive stool examinations for enteric pathogens, pathogenic ova or parasites, or Clostridium difficile toxin at screening.
10. Subjects with clinically significant infections currently or within 6 months of baseline (eg, those requiring hospitalization or parenteral antimicrobial therapy or opportunistic infections), a history of any infection requiring antimicrobial therapy within 2 weeks of baseline, or a history of any infection otherwise judged by the investigator to have the potential for exacerbation by participation in the study
11. Subjects with a history of more than one episode of herpes zoster, a history of disseminated herpes zoster or disseminated herpes simplex.
12. Subjects infected with human immunodeficiency virus (HIV) or hepatitis B or C viruses (Subjects with positive HCV antibody must have further testing for HCV RNA by PCR13. Subjects who hav

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: 17.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Intervention(s)

Product Name: CP-690,550-10
Product Code: CP-690,550-10
Pharmaceutical Form: Tablet
CAS Number: 540737-29-9
Current Sponsor code: CP-690,550-10
Other descriptive name: tofacitinib
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: -To evaluate the safety and tolerability of tofacitinib in subjects with moderately to severely active UC.
-To evaluate the efficacy of tofacitinib in achieving mucosal healing in subjects with moderately to severely active UC.
To evaluate the effect of tofacitinib induction therapy on other clinical outcomes in subjects with moderately to severely active UC.
- To evaluate the tofacitinib pharmacokinetic (PK) exposure during induction therapy in subjects with moderately to severely active UC.
- To evaluate the effect of induction treatment of tofacitinib on quality-of-life in subjects with moderately to severely active UC.

Main Objective: To demonstrate the efficacy of tofacitinib in inducing remission in subjects with moderately to severely active UC.

Primary end point(s): The proportion of subjects in remission at Week 8. Remission is defined by a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point and a rectal bleeding subscore of 0.

Timepoint(s) of evaluation of this end point: Week 8 of treatment

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: All secondary endpoints are evaluated at Week 8 of treatment

Secondary end point(s): Key Secondary Endpoint:
- The proportion of subjects achieving mucosal healing at Week 8. Mucosal healing is defined by Mayo endoscopic subscore of 0 or 1.
Other Secondary Endpoints:
- The proportion of subjects achieving clinical response at Week 8. Clinical response is defined by a decrease from baseline in Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or absolute subscore for rectal bleeding of 0 or 1.
- The proportion of subjects in endoscopic remission at Week 8. Endoscopic remission is defined by Mayo endoscopic subscore of 0.
- The proportion of subjects in clinical remission at Week 8. Clinical remission is defined by a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point.
- The proportion of subjects in symptomatic remission at Week 8. Symptomatic remission is defined by a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point, and both rectal bleeding and stool frequency subscore of 0.
- The proportion of subjects achieving deep remission at Week 8. Deep remission is defined by a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point and a zero on both endoscopic and rectal bleeding subscores.
- Partial Mayo scores and change from baseline over time.
- Change from baseline at Week 8 in total Mayo score.
ther exploratory, pharmacokinetic, biomarker, Health Outcome and safety endpoints are described within the protocol.

Secondary ID(s)

A3921094

2011-004578-27-GB

Source(s) of Monetary Support

Pfizer Inc.