Study to test whether PF-00547659 is safe and improves disease symptoms in patients with Crohn's disease that have not responded to other treatments
- Conditions
- Crohn's DiseaseMedDRA version: 14.1Level: PTClassification code 10011401Term: Crohn's diseaseSystem Organ Class: 10017947 - Gastrointestinal disordersTherapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2010-023437-30-BE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 240
Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in the study.
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study.
1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
2. Subjects are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Male and/or female subjects between the ages of =18 and =75 years. The subject must meet the age criteria at the time of the baseline visit.
4. Active moderate to severe ileal (terminal ileum), ileocolonic, or colonic CD (CDAI scores 220 450).
5. Subjects must have a history of treatment failure or intolerance to either immunosuppressant therapy with azathioprine, 6-mercaptopurine or methotrexate AND/OR anti-TNF monoclonal antibodies:
For Immunosuppressants:
• Treatment failure means continued disease activity despite treatment with a therapeutic dose of azathioprine, 6-mercaptopurine and/or methotrexate.
• Intolerance means that the subject has a history of having experienced an unacceptable or dose limiting toxicity associated with the use of the agent. Examples of intolerance include:
o For azathioprine: severe leucopenia, thrombocytopenia, anemia, severe bone marrow suppression; serious infection; gastrointestinal hypersensitivity; hypersensitivity pancreatitis; or hepatotoxicity manifested by elevation of serum alkaline phosphatase, bilirubin, and/or serum transaminases.
o For 6-mercaptopurine: bone marrow suppression including anemia, leucopenia, thrombocytopenia or hepatotoxicity.
o For methotrexate: immunosuppression, bone marrow, liver (including fibrosis or cirrhosis), lung (including interstitial fibrosis), skin and kidney toxicities.
For anti-TNF Monoclonal Antibodies
• Treatment failure is characterized as either primary non-responsive or relapse.
o Primary Non-Response: Subject experienced no clinical response to at least 1 treatment regimen with an anti TNF with an adequate dose and regimen.
o Relapse: Subject experienced relapse after an initial clinical response or remission to at least 1 anti TNF with an adequate dose and regimen.
• Intolerance is defined as: Clinically significant side effect(s) (including hypersensitivity and development of anti-drug antibodies) to at least 1 treatment regimen with an anti TNF.
6. hsCRP >3.0 mg/L.
7. Ulcerations on colonoscopy performed during screening as defined by the Simple Endoscopic Score – Crohn’s Disease (SES CD). Colonoscopy performed within 8 weeks of screening documenting ulceration and able to retrospectively complete the SES-CD is acceptable.
Note: Colonoscopy to be completed after signing ICD and verification of eligible lab values if required.
8. All women of childbearing potential (WOCBP) must have a negative serum pregnancy test result at screening and a negative urine pregnancy test result at baseline.
Note: A negative urine pregnancy test will also be required for WOCBP prior to each dose.
• WOCBP are defined as women who are biologically capable of becoming pregnant, including women who are using contraceptives or whose sexual partners are either sterile or using contraceptives.
• Women of non childbearing potential (WONCBP) are defined as either po
Subjects presenting with any of the following will not be included in the study:
1. Pregnant or breastfeeding women.
2. Entero vesicular (ie, between the bowel and urinary bladder) fistulae are prohibited. Other fistulae are allowed (eg enterocutaneous fistulae). Documentation of active and inactive fistulae are required.
3. Multiple small bowel resections resulting in clinically significant short bowel syndrome who require TPN.
4. Previous bowel surgery resulting in an existing or current stoma Subjects who have a j-pouch are excluded as a j-pouch can result in a stoma.
5. Surgical bowel resection within the past 3 months.
6. History of diverticulitis or currently symptomatic diverticulosis.
7. 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 weeks prior to study entry. Documentation of the official reading must be located and available in the source documentation).
8. Any history or current evidence of latent or active tuberculosis infection, evidence of prior or currently active tuberculosis by chest radiography, residing with or frequent close contact with an individual with active tuberculosis. Subjects who have a positive Mantoux (PPD) tuberculin skin test or a positive Interferon Gamma Release Assay performed locally (the following are acceptable assay: QuantiFERON® TB Gold test (QFT G), QuantiFERON® TB Gold In Tube test (QFT GIT) and T SPOT® TB test) during screening or within 12 weeks prior to screening.
• A positive Mantoux tuberculin skin test is defined as =5 mm of induration (or as defined by country specific or local standards) at 48 72 hours without consideration of prior Bacillus Calmette-Guérin (BCG) vaccination. Documentation of the dose and product used as well as the official test reading must be obtained and available in the subject's study file.
• An IGRA is preferred for subjects with a prior Bacillus Calmette Guérin (BCG) vaccination (to be tested by the site’s local lab). Documentation of IGRA product used and the test result must be in the subject’s source documentation.
9. Presence of active enteric infections (positive stool culture and sensitivity). The presence of Clostridium difficile or pseudomembranous colitis. Known active invasive fungal infections such as histoplasmosis. Subjects with a clinically significant underlying disease that could predispose the subject to infections. A history of serious infection (requiring parenteral antibiotic and/or hospitalization) within 4 weeks before the randomization visit or baseline visit. Pyoderma gangrenosum is allowed.
10. Preexisting demyelinating disorder such as Multiple Sclerosis or new onset seizures, unexplained sensory, motor, or cognitive, behavioral, neurological deficits, or significant abnormalities noted during screening.
11. 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. (Note: a documented negative HIV test within one year of screening is acceptable and does not need to be repeated).
12. Significant concurrent medical conditions at the time of screening or baseline visit, including, but not limited to, the following:
• Any major illness/condition or evidence of an unstable clinical condition (eg, renal, hepatic, h
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the number of subjects that experience a decrease in CDAI (Crohn’s Disease Activity Index) of at least 70 points by the Week 8 or Week 12 assessment.;Secondary Objective: • To evaluate safety and tolerability<br>• To determine the number of subjects in whom the CDAI is reduced to less than 150 points (ie achieve clinical remission) by Weeks 8 or 12.<br>• To determine the number of subjects that experience remission or response at Weeks 2 through 12.<br>• To evaluate the number of subjects developing anti-drug antibodies to PF-00547659.<br>• To measure the concentration of PF-00547659 and to determine the concentration time curve.;Primary end point(s): CDAI-70 response rate at Week 8 or Week 12.;Timepoint(s) of evaluation of this end point: Week 8 and Week 12
- Secondary Outcome Measures
Name Time Method