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-SE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 262
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 legally acceptable 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), despite use of stable doses of mesalamine (5 ASAs), and/or immunosuppressants (AZA, 6 MP and methotrexate (MTX)).
5. Subjects who are inadequate responders or intolerant to immunosuppressants (AZA
6-MP, and/or MTX).
6. Subjects must have failed or be intolerant to anti TNFs
• Relapse: Subject experienced relapse after an initial clinical response or remission to at least 1 anti TNF with an adequate dose and regimen.
• Primary Non-Responder: Subject experienced no clinical response to at least 1 treatment regimen with an anti TNF with an adequate dose and regimen.
• Intolerant: Subject experienced clinically significant side effect(s) (including hypersensitivity) to at least 1 treatment regimen with an anti TNF.
Note: the above are stratification variables. Primary non responders will be stratified up to 50%. Subjects will also be stratified by concomitant immunosuppressant. Documentation of previous experience with anti TNFs should be recorded in the source documents and appropriate CRF Documentation.
7. hsCRP >3 mg/L.
8. Ulcerations on colonoscopy performed during screening as defined by the Simple Endoscopic Score – Crohn’s Disease (SES CD).
Note: Colonoscopy to be completed after signing ICD and verification of eligible lab values.
9. 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 postmenopausal (history of amenorrhea for =52 weeks) or who are surgically sterile, such as after hysterectomy, bilateral oophorectomy, or tubal ligation (procedure performed =52 weeks before screening). This information must be documented in the subject's source documents.
• WONCBP do not require a serum and urine pregnancy test.
Please refer to the protocol for the full list of inclusion criteria
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 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 120
Subjects presenting with any of the following will not be included in the study:
1. Pregnant or breastfeeding women.
2. Entero vesicular fistulae are prohibited. Other fistulae is allowed (eg enterocutaneous fistulae). Documentation of active and inactive fistulae are required.
3. Short bowel syndrome due to multiple small bowel resections.
4. Previous bowel surgery resulting in an existing or current stoma
5. Surgical bowel resection within the past 3 months.
6. History of diverticulitis or 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 (screening). 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, recent 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 (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. Active enteric infections (stool culture and sensitivity as well as Clostridium difficile toxins A and B to be performed locally (preferred) or at the central laboratory), pseudomembranous colitis, or known active invasive fungal infections such as histoplasmosis. Any underlying disease that could predispose the subject to infections or 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, hematologic, gastrointestinal, endocrine, pulmonary, immunologic [eg, Felty syndrome], or local active infection/infectious illness) that, in the investigator’s judgment, will substantial
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<br>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<br>150 points (ie achieve clinical remission) by Weeks 8 or 12.<br>• To determine the number of subjects that experience remission or response at<br>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 Secondary end point(s): • Safety and tolerability of PF-00547659 dose levels versus placebo: the frequency of<br>treatment adverse events, withdrawal due to adverse events, and serious adverse<br>events (SAEs) will be reported. Any subject who receives at least 1 dose of<br>investigational product will be included in the evaluation for safety.<br>• Percent of subjects with a CDAI remission (CDAI <150), CDAI-70 and CDAI-100<br>responses Weeks 2 through 12 (Day 14 to Day 84).;Timepoint(s) of evaluation of this end point: All visits<br>