A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, DOSE-RANGING STUDY TO EVALUATE THE EFFICACY AND SAFETY OF PF-04236921 IN SUBJECTS WITH CROHN'S DISEASE WHO ARE ANTI-TNF INADEQUATE RESPONDERS
- Conditions
- Crohn's Disease (active moderate to severe)MedDRA version: 14.1Level: LLTClassification code 10013099Term: Disease CrohnsSystem Organ Class: 10017947 - Gastrointestinal disordersTherapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2010-023034-23-IT
- Lead Sponsor
- PFIZER INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 240
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 who 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.
4. Subjects must have failed or are intolerant to anti TNFs
• Relapsed after at least 1 anti TNF.• Primary non-responder to at least 1 anti TNF (maximum 50% of
subjects).
• Intolerant to at least 1 anti TNF
• Other – Discontinued at least 1 anti TNF regimen for other reasons.
(Note: the anti TNF failure type is one of the stratification factors in this
study. Primary non responders will be limited up to 50% of total
enrollment by stratification. Intolerant subjects are those not meeting
one of the prior 2 categories)
5. Active moderate to severe ileal (terminal ileum), ileocolic, or colonic
CD (CDAI scores =220 to =450), despite use of mesalamine (5 ASAs),
and/or immunosupressants (AZA, 6 MP, and MTX) (May continue use of
5 ASAs, AZA, MTX and 6 MP in this trial; dose must be stable 4 weeks
prior to screening visit).
(Note: the background immunosuppressant therapy type (AZA, 6MP,
MTX or none) is another stratification factor in this study.)
6. hsCRP =5 mg/L.
7. Ulcerations demonstrated by colonoscopy performed during screening
as defined by SES CD assessment (Colonoscopy to be completed after
signing ICD and verification of eligible lab values).
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 and throughout the duration of the study.
• 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 and confirmation
by FSH level) 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.
9. WOCBP who have sexual intercourse with a non-surgically sterilized
male must agree and commit to the use of the following highly effective
methods of contraception for the duration of the study (defined as the
time of the signing of the ICF through the conclusion of subject
participation or for approximately 9 months from the last dose of
investigational product for any subject who discontinues early from the
study). Female subjects who meet the criteria will be advised to
continue a highly effective method of birth control for an additional 40
weeks at the conclusion of study participation due to the possible
presence of low levels of investigational product. Contraceptive methods
considered acceptable for use in this study include:
• Established use [=2 months prior to the screening visit] of oral,
injected, transdermal or implanted hormonal methods of contraception.
• Hormonal contraception must be accompanied by the use of a physical
barrier method such as use of a spermicidal condom or occlusive cap
(diaphragm or cervical/vault
Medical History
1. Pregnant or breastfeeding women.
2. CD with active fistulae or abscess. Subjects with a prior history of
fistulae or abdominal or perineal abscess or have not completed the
usual CT/MR work up for extent of disease must have CT or MR
enterography during screening to exclude active fistulae or abdominal or
perineal abscess prior to study entry. MR enterography may be
preferred since it does not have radiation exposure.
3. Subjects who had a colectomy with ileorectal anastomosis, or multiple
small bowel resections resulting in clinically relevant short bowel
syndrome with clinically significant malabsorption or need for TPN, in
the opinion of the Investigator.
4. Previous bowel surgery resulting in a stoma or surgical bowel
resection within the past 3 months.
5. History of diverticulitis or symptomatic diverticulosis.
6. Pre existing demyelinating disorder such as multiple sclerosis, new
onset seizures, unexplained sensory, motor, or cognitive, behavioral or
neurological deficits.
7. 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 12
months of screening is acceptable and does not need to be repeated).
8. 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, GI, endocrine, pulmonary,
immunologic [eg, Felty syndrome], or local active infection/infectious
illness) that, in the investigator's judgment, will substantially increase
the risk to the subject if he or she participates in the study.
• Cancer or history of cancer or lymphoproliferative disease within the
previous 5 years (other than resected cutaneous basal cell or squamous
cell carcinoma that has been treated with no evidence of recurrence).
• Class III or IV congestive heart failure as defined by the New York
Heart Association.
• Acute coronary syndrome (eg, myocardial infarction, unstable angina
pectoris) and any history of significant cerebrovascular disease within
24 weeks before screening.
9. Any major elective surgery scheduled to occur during the study.
10. Presence of a transplanted organ.
11. Prior evidence of liver injury or toxicity due to methotrexate.
Physical and Laboratory Findings
12. Abnormal findings on the a 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).13. 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 individual(s)
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 assays: 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
randomization.
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