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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 6 October 2020
Main ID:  EUCTR2017-002108-28-DE
Date of registration: 27/03/2018
Prospective Registration: Yes
Primary sponsor: Pfizer Inc, 235 East 42nd Street, New York, New York 10017
Public title: A study to evaluate the efficacy, safety, tolerability and pharmacokinetics of PF-06687234/placebo as add-on therapy to infliximab in subjects with ulcerative colitis who are not in remission
Scientific title: A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE EFFICACY, SAFETY, TOLERABILITY AND PHARMACOKINETICS OF PF-06687234 AS ADD-ON THERAPY TO INFLIXIMAB IN ACTIVE ULCERATIVE COLITIS SUBJECTS WHO ARE NOT IN REMISSION (BUILD UC) - BUILD UC
Date of first enrolment: 25/07/2018
Target sample size: 76
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002108-28
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: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes 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 Belgium Germany Israel Italy Korea, Republic of Saudi Arabia Serbia
Spain United States
Contacts
Name: Clinical Trials.gov Call Center   
Address:  235 East 42nd Street NY 10017 New York United States
Telephone: +18007181021
Email: ClinicalTrials.gov_Inquiries@pfizer.com
Affiliation:  Pfizer Inc.
Name: Clinical Trials.gov Call Center   
Address:  235 East 42nd Street NY 10017 New York United States
Telephone: +18007181021
Email: ClinicalTrials.gov_Inquiries@pfizer.com
Affiliation:  Pfizer Inc.
Key inclusion & exclusion criteria
Inclusion criteria:
1. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
3. Male and/or female subjects =18 years to =75 years of age and weight > 40 kg at the time of informed consent. For subjects in South Korea: male and/ or female =19 years to =70 years of age and weight > 40 kg at the time of informed consent.
4. A diagnosis of active UC (histologic) for =4 months. A biopsy report supporting the diagnosis prior to the baseline visit must be available in the source documents. In addition, a report documenting disease duration and extent of disease (eg, proctosigmoiditis, left-sided colitis, or pancolitis) based upon prior endoscopy must also be available in the source documentation.
5. Subjects who have partial response to anti-TNF (infliximab) and active UC as defined by (via screening endoscopy) a total Mayo Score =5 but =9 and an endoscopic subscore =2. Endoscopy (flexible sigmoidoscopy or colonoscopy), should be performed within 14 days of baseline (Day 1). The endoscopic Mayo subscore assessed by the Central Reader must be available at the baseline visit. The assessment by the Central Reader will be used to derive the total Mayo score to determine study eligibility. Primary non-responder to anti-TNF therapy should be excluded.
6. UC extending at least 25 cm proximal to the anal verge at the time of the screening endoscopy. Only a portion, of the 25 cm of involved colon must be graded with Mayo endoscopic subscore of 2.
7. Must be on a stable dose 5- to 10 mg/kg of Remicade® or protocol specified infliximab biosimilars (see Protocol Appendix 5) for a minimum of 14 weeks (4 doses) and a maximum of two years prior to study entry with no anticipation of need for change in infliximab treatment regimen throughout the study (no switches from pre-study infliximab version to a different infliximab version will be permitted through Week 12). For a subject who has recently switched dose or dosing intervals of infliximab during maintenance therapy, the subject must be on the same dose and dosing interval for at least two treatment cycles (minimum 12 weeks) before study entry. Subject must maintain the same infliximab regimen of every 6 weeks or every 8 weeks throughout the study.
8. Subjects currently receiving the following treatment for UC are eligible provided they have been on stable doses as described below:
- Oral 5-aminosalicylic acid derivative (5-ASA) or sulfasalazine stable dose for at least 4 weeks prior to baseline. If oral 5-ASA treatment has been recently discontinued, it must have been stopped for at least 2 weeks prior to date of total Mayo Score assessment.
- Oral corticosteroids (prednisone equivalent up to 20 mg/day; budesonide up to 9 mg/day) stable dose for at least 2 weeks prior to baseline. If oral corticosteroids have been recently discontinued, they must have been stopped at least 2 weeks prior to date of total Mayo Score assessment. Decreases in steroid use due to AEs are allowed.
- 6-MP, azathioprine (AZA) (= 2.5 mg/kg), or MTX stable dose for 8 weeks prior to baseline.
9. Male subjects able to father children and female subjects of childbearing potential and at risk for pregnancy must agree to use two methods of contraception throughout the study and until the Week 16 visit (or 28 days after th

Exclusion criteria:
1. Pregnant female subjects; breastfeeding female subjects (S.); fertile male S. & female S. of childbearing potential who are unwilling or unable to use 2 methods of contraception as per protocol for the duration of the study (Wk16 visit) or for at least 28days (d.) after the last dose of IP
2. S. with a diagnosis or documented history of total colectomy &/or pouchitis, indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, & diverticular disease associated with colitis, or clinical findings suggestive of Crohn's disease
3. S. considered in imminent need for surgery or with major elective surgery scheduled to occur during the study
4. S. with extensive colitis for at least 8yrs who have not had a colonoscopy with surveillance biopsies within 2yrs of the baseline visit
5. S. with history of or at screening endoscopy, biopsy documented colonic dysplasia or neoplasia. S. with prior history of adenomatous polyps will be eligible if the polyps have been completely removed & pathology is negative.
6. S. who require infliximab dosing interval other than every 8wks during this study
7. S. displaying clinical signs of fulminant colitis or toxic megacolon
8. S. with primary sclerosing cholangitis
9. S. with known colonic stricture, or history of colonic or small bowel obstruction or resection
10. S. with history of or current colonic or small bowel stoma
11. History of known cyclic neutropenia, thrombocytopenia, lymphopenia, leukopenia or any history of chronic anemia (HGB<10g/dL) which is judged by the investigator (inv.) to have an unclear specific etiology or is non self-limiting
12. 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 12wks prior to screening. Documentation of the official reading must be located and available in the source documentation
13. Current evidence of active TB or latent TB infection or inadequately treated TB infection demonstrated by chest x-ray, a positive Mantoux (PPD) tuberculin skin test or a positive Interferon Gamma Release Assay during screening or within 12wks prior to randomization. The following are acceptable assays: QFT-G, QFT-GIT and T-SPOT® - TB test during screening or within 12wks prior to screening
14. Presence of active enteric infections (positive stool culture & sensitivity). The presence of Clostridium difficile infection or pseudomembranous colitis or history of recurrent Clostridium difficile infection. Known active invasive fungal infections such as histoplasmosis or parasitic infections
15. 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 & as per local regulations
16. Presence of transplanted organ; skin grafts are allowed
17. Previous severe hypersensitivity reaction to infliximab or known hypersensitivity to inactive components of infliximab or to any murine protein
18. Exposure to a live (attenuated) vaccine within 30d. prior to screening or anticipated need for any live (attenuated) vaccine during the study
19. Significant concurrent medical condition at the time of baseline visit
20. S. receiving the therapies described in Protocol Sec. 4.2 within the designated time period or are expected to receive any of these therapies


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
Ulcerative colitis
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856
Intervention(s)

Product Name: Dekavil
Product Code: PF-06687234
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: PF-06687234
Current Sponsor code: PF-06687234
Other descriptive name: F8IL10
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Powder for solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)
Main Objective: • To evaluate the efficacy of PF-06687234 in induction of clinical remission in subjects with UC and a partial response to anti-TNF-a;
• To evaluate the safety and tolerability of PF-06687234 in subjects with UC and a partial response to anti-TNF-a.
Primary end point(s): • Proportion of subjects in clinical remission at Week 12 (as defined by a modified total Mayo Score with traditional endoscopic subscore =1, stool frequency subscore =1 and rectal bleeding subscore = 0).
• Incidence and severity of adverse events, serious adverse events and withdrawals due to adverse events, ECGs, vital signs and safety laboratory tests.
Secondary Objective: • To evaluate the efficacy of PF-06687234 in induction of endoscopic improvement in subjects with UC and partial response to anti-TNF-a;
• To evaluate histological improvement in subjects with UC and partial response to anti-TNF-a;
• To evaluate the efficacy of PF-06687234 in induction of clinical response in subjects with UC and a partial response to anti-TNF-a.
• To describe the PK of PF-06687234 in subjects with UC.
• To evaluate the immunogenicity of PF-06687234 in subjects with UC.
Timepoint(s) of evaluation of this end point: The primary endpoint will be analyzed at Week 12 using exact Chan and Zhang method. The difference between treatment groups in the proportion of subjects in remission at Week 12 will be presented along with its 95% confidence interval. Subjects with missing remission data at Week 12 will be treated as treatment failure. As sensitivity analyses, the primary endpoint will also be analyzed using other methods for handling missing data which will be described in the SAP.
All clinical AEs, SAEs, TEAEs, withdrawal due to AEs, ECGs (on weeks 6,12,16), vital signs and safety laboratory data (on weeks 1,2,4,6,8,10,12,16) will be reviewed and summarized on an ongoing basis in a blinded manner during the study to evaluate the safety of subjects.
Secondary Outcome(s)
Secondary end point(s): • Proportion of subjects with endoscopic improvement at Week 12 (defined as decrease of =1 point in modified endoscopic subscore or an absolute endoscopy score of =1).
• Mean change from baseline at Week 12 in Geboes histology score.
• Proportion of subjects with a clinical response at Week 12 defined with a decrease from baseline of at least 3 points in total Mayo score with at least 30% change, accompanied by at least one point decrease or absolute score of 0 or 1 in rectal bleeding subscore.
• Proportion of subjects with change from baseline in partial Mayo Score of =2 with no individual subscore >1 at Weeks 2, 4, 6, 8, 12.
• Serum concentrations of PF-06687234.
• Incidence of the development of HAFAs and Nabs against PF-06687234.
Timepoint(s) of evaluation of this end point: The proportion of subjects achieving endoscopic improvements or clinical response will be analyzed using same approach as for primary endpoint.
Change from baseline at Week 12 in Geboes histology score will be analyzed using analysis of covariance model with treatment group and baseline scores. Proportions of subjects with partial Mayo Score will be analyzed using generalized linear mixed effect model with treatment group, visit, treatment group by visit interaction and subjects as random effect.
PK concentration population: as all enrolled subjects who received at least one IP dose and in whom at least one concentration value is reported.
Immunogenicity assessment population: as all enrolled subjects who received at least one IP dose with at least one post-treatment HAFA determination.
Secondary ID(s)
122507
2017-002108-28-BE
B7581002
NCT03269695
Source(s) of Monetary Support
Pfizer Inc.
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date: 25/07/2018
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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