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 Responsers

• Register: EUCTR
• Last refreshed on: 13 March 2017
• Main ID: EUCTR2010-023034-23-IE
• Date of registration: 07/04/2011
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc., 235 East 42nd Street, New York, NY 10017
• Public title: 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 Responsers
• Scientific title: 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 (ANDANTE) - ANDANTE
• Date of first enrolment: 03/06/2011
• Target sample size: 220
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-023034-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Dose Ranging If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Brazil, Canada, Czech Republic, Denmark, France, Germany, Greece, Hungary, Ireland, Israel, Italy, New Zealand, Sweden, Switzerland, United Kingdom, United States

Contacts

• Name: Clinical Trials.gov Call Centre
• Affiliation: Pfizer Inc

• Name: Clinical Trials.gov Call Centre
• Affiliation: Pfizer Inc

Key inclusion & exclusion criteria

Inclusion criteria:
1. Evidence of personally signed & dated informed consent document indicating.
2. Subjects willing & able to comply with scheduled visits, & other study procedures.
3. Subjects between ages of =18 &=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 ; Intolerant to at least 1 anti TNF; Other – Discontinued at least 1 anti TNF regimen for other reasons.
5. Active moderate to severe ileal (terminal ileum), ileocolic or colonic CD (CDAI scores =220 to =450), despite previous or current use of conventional therapies including mesalamine (5 ASAs), oral steroids and/or immunosupressants (AZA, 6 MP, & MTX) (May continue use of 5 ASAs, AZA, MTX, 6 MP and oral steroids in this trial; dose should be stable 2 weeks prior to randomization). (Note: current use of immunosuppressant therapy type (AZA, 6MP, MTX or none) is another stratification factor in this study.)
6. hsCRP =5.0 mg/L.
7. Ulcerations demonstrated by colonoscopy as defined by the Simple Endoscopic Score– Crohn’s Disease (SES-CD). Colonoscopy performed within 8 weeks of study entry (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 negative urine pregnancy test result at baseline and throughout study duration. WOCBP are defined as women biologically capable of becoming pregnant, including women using contraceptives or whose sexual partners are either sterile or using contraceptives; WONCBP are defined as either postmenopausal (history of amenorrhea for =52 weeks and confirmation by FSH level) or who are surgically sterile as after hysterectomy, bilateral oophorectomy or tubal ligation (procedure performed =52 weeks before screening). This information must be documented in 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 following highly effective methods of contraception for the duration of the study (defined as the time of the signing of the ICD through the conclusion of subject participation or for approximately 36 weeks from the last dose of investigational product for any subject who discontinues early from the study). Female subjects who meet criteria will be advised to continue a highly effective method of birth control for additional 40 weeks at conclusion of study participation due to possible presence of low levels of investigational product. Contraceptive methods considered acceptable for use in this study include:
(a) Established use [=2 months prior to the screening visit] of oral, injected, transdermal or implanted hormonal methods of contraception. Subjects who have used such methods for less than 2 months at the screening visit are required to use one of the methods under c) or d) until the establishment of hormonal contraception methods.
(b)Hormonal contraception must be accompanied by use of a physical barrier method such as use of a spermicidal condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ suppository. In countries where spermicidal condoms are not allowed ordinary condoms could be used in
Exclusion criteria:
Subjects presenting with any of the following will not be included in the study: Medical History:
1. Pregnant or breastfeeding women.
2. CD with active fistulae or abscess. CT or MR enterography is required within 6 months prior to study entry (screening) to exclude active fistulae (one that drains spontaneously or with gentle pressure) or abdominal or perineal/perianal abscess. Small bowel series could be performed if CT/MR enterography is not accessible or cannot be performed within the screening period.
3. Subjects who had a total colectomy with ileorectal anastomosis. Multiple small bowel resections resulting in clinically significant short bowel syndrome with malabsorption or need for TPN.
4. Presence of a bowel stoma. 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. Methotrexate use with evidence of current or prior liver injury or toxicity (increase in ALT/AST or fibrosis).
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 (screening). 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 or central lab where applicable (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 t

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Crohn's Disease (active moderate to severe)
MedDRA version: 16.1 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Name: Not Applicable
Product Code: PF-04236921
Pharmaceutical Form: Powder for injection
INN or Proposed INN: Not Applicable
Current Sponsor code: PF-04236921
Other descriptive name: The investigational medicinal product (IMP) may be labelled as either “PF-04236921 106 mg/vial, Clonal SC lyophilized form” or “PF-04236921 Powder for Injection, 106 mg/vial”. Supplies labelled with either nomenclature are equivalent.
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 106-
Pharmaceutical form of the placebo: Powder for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 8 or Week 12

Primary end point(s): The CDAI 70 response rate at Week 8 or Week 12

Main Objective: The primary objectives of this study are to demonstrate clinical activity of PF 04236921 that will induce a clinical response and remission in subjects with Crohn’s Disease (CD) via the Crohn’s Disease Activity Index (CDAI) and to select dose(s) for future clinical studies.

Secondary Objective: The secondary objectives include:
• Evaluate safety, tolerability, and immunogenicity of PF-04236921.
• Characterize PK of PF-04236921 in subjects with CD.

Exploratory Objectives
• Explore the relationship between PK/PD and CDAI score and biomarkers.
• Characterize PD and other biomarkers
• Assess health outcome measures in IBDQ and EQ 5D™.

Secondary Outcome(s)

Secondary end point(s): • Percent of subjects with a CDAI remission (CDAI <150), CDAI 70 and CDAI 100 responses Weeks 2 through 12 (Day 14 to Day 84).
• Mean change from baseline for CDAI score Weeks 2 through 12 (Day 14 to Day 84).
• Safety and tolerability of PF-04236921 dose levels versus placebo: the frequency of on treatment adverse events, withdrawals due to adverse events, and SAEs will be reported. Any subject who receives at least 1 dose of investigational product will be included in the evaluation for safety.
• Percent of subjects that develop ADAs and NAbs, if observed, measured at baseline, and Weeks 4, 8, 12, 16, 24, 32 and 40 will be reported.
• Serum concentrations of PF-04236921 measured at baseline and every two weeks up to Week 12 and monthly through Week 40 will be reported.

Timepoint(s) of evaluation of this end point: The timepoints are defined with the secondary endpoints

Secondary ID(s)

B0151003

NCT01345318

Source(s) of Monetary Support

Pfizer Inc