A MULTICENTER OPEN-LABEL EXTENSION STUDY FOR SUBJECTS WHO PARTICIPATED IN STUDY B0151003

• Register: EUCTR
• Last refreshed on: 24 October 2016
• Main ID: EUCTR2011-000722-30-CZ
• Date of registration: 21/03/2012
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc.
• Public title: A MULTICENTER OPEN-LABEL EXTENSION STUDY FOR SUBJECTS WHO PARTICIPATED IN STUDY B0151003
• Scientific title: A MULTICENTER OPEN-LABEL EXTENSION STUDY FOR SUBJECTS WHO PARTICIPATED IN STUDY B0151003 (ANDANTE II) - ANDANTE II
• Date of first enrolment: 12/11/2012
• Target sample size: 160
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-000722-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 2
• 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, Romania, 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:
Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in this study.
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into this study:
1. Subjects previously enrolled in study B0151003 and completed the blinded 84 day (12 week) induction period.
2. Evidence of a personally signed and dated informed consent document (ICD) indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
3. All women of childbearing potential (WOCBP) as determined during study B0151003 (data must be available as source documents for this study) must have a negative urine pregnancy test result at the baseline (Week 12 [Day 84] visit of B0151003) visit and at specified visits during this study (defined as the time of the signing of the ICD through the end of this study). A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is
sexually active.
• Women of nonchildbearing potential as determined during the previous study do not require urine pregnancy tests in this study.
4. WOCBP who have sexual intercourse with a non surgically sterilized male partner must agree and commit to the use of the two highly effective methods of birth control from signing the ICD through the Final Study Evaluation.
Note: The subject is strongly advised to continue a highly effective birth control for an additional 26 weeks after the Final Study Evaluation due to the possible presence of measurable investigational product. If the subject withdrawals early from the study and refuses to return for the recommended follow up visit schedule, they will be strongly advised to continue a highly effective birth control for 62 weeks from their last dose of investigational product.
Contraceptive methods considered acceptable for use in this study include:
• Established use of oral, injected, transdermal, or implanted hormonal methods of contraception (data must be available as source documents for this study).
• 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 caps) with spermicidal foam/gel/film/cream/suppository. In countries where spermicidal
condoms are not allowed, ordinary condoms could be used in combination with spermicidal creams.
• Double barrier contraception: Condom and Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository. A female condom and a male condom should not be used together as friction between the two can result in either, or both, product(s) failing.
• An intrauterine device or system. An additional barrier method
(condom or spermicide) are encouraged.
5. All men (unless surgically sterile, as defined below) who have sexual intercourse with a WOCBP must agree and commit to use a highly effective method of contraception as described under WOCBP for the duration of this study (defined as the time of signing the ICD through the Final Study Evaluation). Highly effective methods of contraception include properly used spermicidal condom.
Note: The subject is strongly advised to continue a highly effective birth control for an additional 26 weeks after the Final Study Evaluation due to the possible presence of measurable investigational
Exclusion criteria:
Subjects presenting with any of the following will not be included in this study:
1. Subjects who are investigational site staff members and their family members or subjects who are Pfizer employees and their family members directly involved in the conduct of the trial.
2. Subjects that have completed Day 84 (Week 12) visit of study B0151003, and experienced serious event(s) related to the investigational product, an unstable medical condition, or any other reason, in the opinion of the investigator, would preclude entry or inclusion in this study.
3. Pregnant or breastfeeding women.
4. Other severe acute or chronic medical or psychiatric condition or
laboratory abnormality that may increase the risk associated with study participation or ability to comply with study procedures, investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
5. Received any prohibited treatment during study B0151003 that, in the opinion of the investigator, compromised the safety or efficacy of this study.
6. Planned live (attenuated) vaccination during the course of this study.
7. Planned major elective medical or surgical procedure during the course of this study.
8. Participation in other studies during participation in this study.



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

Health Condition(s) or Problem(s) studied

Crohn’s disease
MedDRA version: 18.0 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-

Primary Outcome(s)

Main Objective: The primary objective of this study is to evaluate the long term safety, tolerability, and immunogenicity of PF-04236921.

Primary end point(s): Any subject who receives at least 1 dose of investigational product will be included in the evaluation for safety. The frequency of on-treatment AEs, withdrawals due to AEs, and SAEs will be reported. Percent of subjects that develop ADAs and NAbs will be reported, if observed, at baseline (Week 12 [Day 84] visit of B0151003) or when tested every 8 weeks through Week 76 (FSE).

Secondary Objective: The exploratory objectives include assessment of the proportion of subjects in remission, relapse rates, response rates, and the need for dose escalation. Additionally, population PK and biomarkers will be assessed.

Timepoint(s) of evaluation of this end point: Evalution of the end points will occur during each visit detailed in the protocol

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Timepoints defined within the secondary endpoints

Secondary end point(s): PK:For the serum concentration data obtained from all subjects at visits every 4 weeks up to Week 76 (FSE) in this study will be combined and compared with serum concentration data collected from the same subjects that participated in the previous study (B0151003). The combined data may be analyzed using the population PK methodology as appropriate.
PK/PD: Pharmacodynamic (PD) parameters will be assessed through blood samples collected at baseline (Week 12 [Day 84] visit of B0151003) and Week 4 (Visit 2), and then every 4 weeks up to Week 76 (FSE) to measure high sensitivity C-reactive protein (hsCRP), total IL-6, and free IL-6. Not all IL6 samples collected at all time will be analyzed; some may be stored for future analysis. Also, stool samples will be collected at baseline (Week 12 [Day 84] visit of B0151003) and Week 4 (Visit 2), and then every 8 weeks through Week 44 (Visit 12) to measure fecal calprotectin. Exploratory PK/PD modeling may be performed to define dose and exposure response relationships for PD biomarkers (eg, free and total IL-6) and clinical efficacy endpoints (eg, HBI scores). Results of the exploratory analysis (if conducted) would be reported separately from the clinical study report, but the data listing will be provided in final report.

Efficacy: Any subject who receives at least 1 dose of investigational product will be included in the evaluation for efficacy. The HBI will be used to assess disease activity.
• Change in the HBI will be used to assess clinical efficacy during this open label extension study.
• Remission will be defined as an HBI activity score of less than 5.
• Response at the baseline in the current study (B0151005) is defined as a decrease of =70 Crohn’s Disease Activity Index (CDAI) points at Week 12 in the previous study B0151003. Response at a certain later time point is defined as meeting either of the following two conditions:
1. Being a responder at baseline and never relapsed by that time point. (See Table 1 for the definition of relapse).
2. Having a HBI score decrease of =3 points at that time point from the baseline of either the current study (B0151005) or the previous study B0151003. This condition applies to patients that are non-responders at baseline or relapse after baseline.
Note: The change from the baseline of the previous study B0151003 will be calculated by (? HBI1003 + ? HBI1005), where ? HBI1005 is the change from the baseline of the current study (B0151005), and ? HBI1003 is the change from baseline to Week 12 in the previous study B0151003. The ?HBI1003 calculations will be performed in the CRF Health Trial Manager and be provided to the investigator through the online report tool.
• A non responder will be defined as subject that does not have a response as defined above.
• A relapse is only measured in subjects who have had a response. Relapse is defined as an increase of =3 points in the HBI from the lowest measured HBI on study and the total HBI score being =8. The time to relapse will be captured. In subjects that relapse, the dose may be escalated and the HBI score will be assessed at the subject’s next study visit to evaluate response.
The following analyses will be performed to explore efficacy stratified by responder/non-responder status from study B0151003:
• Proportion of subjects in remission (HBI <5).
• Proportion of subjects with a response (as defined above).
• Percent of subjects requiring dose escalation.
• Percent of subjects discontinued from the study by Week 16.
• Percent of subjects remaining in the study.
• Time to relapse.

Secondary ID(s)

B0151005

2011-000722-30-GB

Source(s) of Monetary Support

Pfizer Inc