A study to evaluate the efficacy, safety, tolerability and pharmacokinetics of PF-06687234/placebo as add-on therapy to infliximab in subjects with ulcerative colitis who are not in remissio
- Conditions
- lcerative colitisMedDRA version: 20.1Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 100000004856Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2017-002108-28-BE
- Lead Sponsor
- Pfizer Inc, 235 East 42nd Street, New York, New York 10017
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 76
1. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
3. Male and/or female subjects =18 years to =75 years of age and weight > 40 kg at the time of informed consent. For subjects in South Korea: male and/or female =19 years to <70 years of age and weight >40 kg at the time of informed consent.
4. A diagnosis of active UC (histologic) for =4 months. A biopsy report supporting the diagnosis prior to the baseline visit must be available in the source documents. In addition, a report documenting disease duration and extent of disease (eg, proctosigmoiditis, left-sided colitis, or pancolitis) based upon prior endoscopy must also be available in the source documentation.
5. Subjects who have partial response to anti-TNF (infliximab) and active UC as defined by (via screening endoscopy) a total Mayo Score =4 but =
9 and an endoscopic subscore =2. Endoscopy (flexible sigmoidoscopy or colonoscopy), should be performed within 14 days of baseline (Day 1).
The endoscopic Mayo subscore assessed by the Central Reader must be available at the baseline visit. The assessment by the Central Reader will
be used to derive the total Mayo score to determine study eligibility.
Primary non-responder to anti-TNF therapy should be excluded.
6. UC extending at least 15 cm proximal to the anal verge at the time of the screening endoscopy.
7. Must be on a stable dose 5- to 10 mg/kg of Remicade® or protocol specified infliximab biosimilars (see Protocol Appendix 5) for a minimum
of 14 weeks prior to study entry with no anticipation of need for change in infliximab treatment regimen throughout the study (no switches from
infliximab version at baseline to a different infliximab version will be permitted through Week 12). For a subject who has recently switched
dose or dosing intervals of infliximab during maintenance therapy, the subject must be on the same dose and dosing interval for at least two
treatment cycles (minimum 12 weeks) before study entry. Subject must maintain the same infliximab regimen of every 6 weeks or every 8 weeks
throughout the study.
8. Subjects currently receiving the following treatment for UC are eligible provided they have been on stable doses as described below:
- Oral 5-aminosalicylic acid derivative (5-ASA) or sulfasalazine stable dose for at least 4 weeks prior to baseline. If oral 5-ASA treatment has been recently discontinued, it must have been stopped for at least 2 weeks prior to date of total Mayo Score assessment.
- Oral corticosteroids (prednisone equivalent up to 20 mg/day; budesonide up to 9 mg/day) stable dose for at least 2 weeks prior to baseline. If oral corticosteroids have been recently discontinued, they must have been stopped at least 2 weeks prior to date of total Mayo Score assessment. Decreases in steroid use due to AEs are allowed.
- 6-MP, azathioprine (AZA) (= 2.5 mg/kg), or MTX stable dose for 8 weeks prior to baseline.
9. Male subjects able to father children and female subjects of childbearing potential and at risk for pregnancy must agree to use two methods of contraception throughout the study and until the Week 16 visit (or 28 days after the last dose of IP).
- Women of childbearing potential (WOCBP) will be eligible provided these women use two methods of contraception throughout
1. Pregnant female subjects; breastfeeding female subjects; fertile male subjects and female subjects of childbearing potential who are unwilling or unable to use 2 methods of contraception as per protocol for the duration of the study (Wk16 visit) or for at least 28days after the last dose of IP
2. Subjects with a diagnosis or documented history of total colectomy and/or pouchitis, indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, and diverticular disease associated with colitis, or clinical findings suggestive of Crohn’s disease
3. Subjects considered in imminent need for surgery or with major elective surgery scheduled to occur during the study
4. Subjects with extensive colitis for at least 8yrs who have not had a colonoscopy with surveillance biopsies within 2yrs of the baseline visit
5. Subjects with history of or at screening endoscopy, biopsy documented colonic dysplasia or neoplasia. Subjects with prior history of adenomatous polyps will be eligible if the polyps have been completely removed and pathology is negative
6. Subjects who require infliximab dosing interval other than every 8wks during this study
7. Subjects displaying clinical signs of fulminant colitis or toxic megacolon
8. Subjects with primary sclerosing cholangitis
9. Subjects with known colonic stricture, or history of colonic or small bowel obstruction or resection
10. Subjects with history of or current colonic or small bowel stoma
11. History of known cyclic neutropenia, thrombocytopenia, lymphopenia, leukopenia or any history of chronic anemia (HGB<10g/dL) which is judged by the investigator to have an unclear specific etiology or is non self-limiting
12. Abnormal findings on the chest x-ray film performed routinely before initiating a new biologic therapy, such as presence of tuberculosis (TB), general infections, heart failure, or malignancy. Chest x-ray examination may be performed up to 12wks prior to screening. Documentation of the official reading must be located and available in the source documentation
13. Current evidence of active TB or latent TB infection or inadequately treated TB infection demonstrated by chest x-ray, a positive Mantoux(PPD) tuberculin skin test or a positive Interferon Gamma Release Assay during screening or within 12wks prior to randomization. The following are acceptable assays: QFT-G, QFT-GIT and T-SPOT® - TB test during screening or within 12wks prior to screening.
14. Presence of active enteric infections (positive stool culture and sensitivity). The presence of Clostridium difficile infection or pseudomembranous colitis or history of recurrent Clostridium difficile infection. Known active invasive fungal infections such as histoplasmosis or parasitic infections.
15. Known history of HIV based on documented history with positive serological test, or positive HIV serologic test at screening, tested at the site’s local lab and as per local regulations
16. Presence of transplanted organ; skin grafts are allowed
17. Previous severe hypersensitivity reaction to infliximab or known hypersensitivity to inactive components of infliximab or to any murine protein.
18. Exposure to a live (attenuated) vaccine within 30days prior to screening or anticipated need for any live (attenuated) vaccine during the study
19. Significant concurrent medical condition at the time of baseline visit
20. Subjects receiving the therapies described in Protocol Sec. 4.2 within the designated time peri
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method