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-ES
- 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
- 98
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.
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 with active UC as defined by (via screening endoscopy) a total Mayo Score =5 but =8 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.
6. UC extending at least 25 cm proximal to the anal verge at the time of the screening endoscopy. Only a portion, of the 25 cm of involved colon must be graded with Mayo endoscopic subscore of 2.
7. Must be on a stable dose 5-10 mg/kg of Remicade®, Inflectra™ or Remsima® for a minimum of 14 weeks (4 doses) and a maximum of two years prior to study entry with no anticipation of need for change in infliximab treatment regimen throughout the study (no switches from pre-study infliximab version to a different infliximab version will be permitted).
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 the study and until the Week 16 visit (or 28 days after the last dose of IP), as outlined in Protocol Section 4.4.
- Female subjects of nonchildbearing potential must meet at least 1 of the following criteria:
Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed with a serum follicle-stimulating hormone (FSH) level confirming the postmenopausal state;
- Have undergone
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 28 days 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 8 yrs who have not had a colonoscopy with surveillance biopsies within 2 yrs of the first screening visit 5. Subjects with history of or at screening endoscopy, biopsy documented colonic dysplasia or neoplasia 6. Subjects who require infliximab dosing interval other than every 8 wks 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 <10 g/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 12 wks prior to screening. Documentation of the official reading must be located and available in the source documentation 13. Any history of either latent or active TB infection, current treatment for active or latent TB infection or evidence of currently active TB by chest x-ray, residing with or frequent close contact with individual(s) with active TB. Subjects who have a positive Mantoux (PPD) tuberculin skin test or a positive Interferon Gamma Release Assay during screening or within 12 wks prior to randomization. The following are acceptable assays: QFT-G, QFT-GIT and T-SPOT® - TB test during screening or within 12 wks 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 designat
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