Study to test whether PF-00547659 is safe and improves symptoms in patients with UC

• Register: EUCTR
• Last refreshed on: 12 September 2016
• Main ID: EUCTR2012-002030-37-CZ
• Date of registration: 16/05/2013
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc, 235 East 42nd Street, New York, NY10017, United States
• Public title: Study to test whether PF-00547659 is safe and improves symptoms in patients with UC
• Scientific title: A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, PARALLEL, DOSE-RANGING STUDY TO EVALUATE THE EFFICACY AND SAFETY OF PF-00547659 IN PATIENTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS (TURANDOT) - TURANDOT
• Date of first enrolment: 30/05/2013
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002030-37
• 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: 5
• 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, Bulgaria, Canada, Croatia, Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, Korea, Republic of, Netherlands, New Zealand, Norway, Poland, Russian Federation, Serbia, Slovakia, South Africa, Spain, Sweden, United Kingdom, United States

Contacts

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

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

Key inclusion & exclusion criteria

Inclusion criteria:
1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
2. Subjects are willing and able to participate in the study, complete subject assessments, attend scheduled clinic visits, and comply with all protocol requirements as evidenced by written informed consent.
3. Male and/or female subjects between the ages of =18 and =65 years at the time of informed consent.
4. A diagnosis of UC for =3 months. A biopsy report must be available to confirm the histological diagnosis in the subject’s source documentation. In addition, a report documenting disease duration and extent of disease (e.g., proctosigmoiditis, left-sided colitis and pancolitis) based upon prior colonoscopy must also be available in source documentation. NOTE: A colonoscopy with biopsy will need to be performed, if this documentation is not available.
5. Must have a flexible sigmoidoscopy (or colonoscopy, if preferred) indicative of active UC (Mayo endoscopic subscore of at least 2) during screening after all other inclusion criteria have been met.
6. Must have active disease beyond the rectum (>15 cm of active disease at the Screening endoscopy).
7. Must have active UC with a Total Mayo Score of 6 to 12 points and moderate to severe disease on endoscopy (Mayo endoscopic subscore of at least 2).
8. Must have failed or been intolerant of at least one conventional therapy such as mesalamine, steroids and immunosuppressants (AZA, 6-MP or MTX) or anti-TNF. Subjects will be stratified based upon prior experience with anti-TNFs (naïve or experienced). Documentation of the current and prior UC treatment (ie, steroids and immunosuppressants) will be captured for additional analyses and must be provided in the source documentation.
9. Male and female subjects of childbearing potential must agree to use a highly effective method of contraception (defined at the time of signing the informed consent) throughout the study and through the conclusion of subject participation. 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 childbearing potential (WOCBP) must have a negative serum pregnancy test result at screening and a negative urine pregnancy test result at baseline. 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) do not require a serum and urine pregnancy test and must meet at least one of the following criteria:
• Have undergone hysterectomy or bilateral oophorectomy;
• Have medically confirmed ovarian failure or
• Are medically confirmed to be post-menopausal (cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; laboratory confirmation of FSH level may be indicated if subject has history of amenorrhea for = 52 weeks).

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 300
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Subjects with a diagnosis of indeterminate colitis or Crohn’s disease. Subjects with clinical findings suggestive of Crohn’s disease, e.g., fistulae or granulomas on biopsy are also excluded.
2. Subjects with an imminent need for or planned surgery.
3. Subjects with colonic dysplasia or neoplasia.
4. Subjects with toxic megacolon.
5. Subjects with primary sclerosing cholangitis.
6. Subjects with known colonic stricture.
7. Subjects with a history of colonic or small bowel obstruction or resection.
8. 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).
9. 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 (IGRA to be tested at the site’s local lab) during screening or within 12 weeks prior to randomization. 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 screening.
10. Presence of active enteric infections (positive stool culture and sensitivity). Please refer to the Protocol Amendment 2 for full exclusion criteria 10.
11. Pre-existing demyelinating disorder such as Multiple Sclerosis or new onset seizures, unexplained sensory motor, or cognitive behavioral, neurological deficits, or significant abnormalities noted during screening.
12. 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).
13. Presence of transplanted organ. Skin grafts to treat pyoderma gangrenosum are allowed.
14. Significant concurrent medical condition 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 that, in the investigator’s judgement 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).
• Right or left heart failure including symptomatic diastolic dysfunction or unexplained elevation of troponin I (>0.05 ng/mL). Subjects with screening or baseline value of NTproBNP >124 pg/mL must have an echocardiogram and cardiology consult that excludes right or left heart failure.
• Acute coronary syndrome and any history of significant cerebrovascular disease within 24 weeks before screening.
15. Any major elective surgery scheduled to occur during the study.
16. Prior evidence of liver injury or toxicity due to methotrexate.
17. Abnormality in hematology and/or chemistry profiles during screening:
18. IV or IM (parenteral) st

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 (UC)
MedDRA version: 17.0 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Intervention(s)

Product Code: PF-00547659
Pharmaceutical Form: Solution for injection
Current Sponsor code: PF-00547659
Other descriptive name: Anti-MAdCAM antibody
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: • To characterize the dose-response and efficacy of PF-00547659 in inducing clinical remission based upon Mayo Score in subjects with moderate to severe ulcerative colitis.

Primary end point(s): • Proportion of subjects in Clinical Remission at Week 12 as defined by a Total Mayo Score of 2 points or lower with no individual subscore exceeding 1 point and rectal bleed subscore of 0 or 1.

Secondary Objective: Secondary Objectives
• To evaluate the induction of clinical response based upon Mayo Score in subjects with moderate to severe ulcerative colitis.
• To evaluate the safety and tolerability of PF-00547659 in subjects with moderate to severe ulcerative colitis.
• To assess the PF-00547659 concentration time course.
• To evaluate the effect of induction treatment of PF-00547659 on quality-of-life in subjects with moderately to severely active ulcerative colitis.

Exploratory Objective
To explore the relationship between PK, PD, and clinical endpoints.

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

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Weeks 4, 8, and 12

Secondary end point(s): Secondary Endpoints
• Proportion of subjects with a Clinical Response at Week 12 with a decrease from baseline in Total Mayo Score by at least 3 points and at least 30% decrease in subscore for rectal bleeding of at least 1 point or absolute subscore of 0 or 1.
• Proportion of subjects with mucosal healing at Week 12 (defined as absolute Mayo subscore for endoscopy of 0 or 1).
• Proportion of subjects with change from baseline in partial Mayo Score of = 2 with no individual subscore >1 at Weeks 4, 8, 12.
• Change from baseline in Mayo Score and in individual Mayo subscores at Weeks 4, 8, and 12.
• Change from baseline in fecal calprotectin at Weeks 4, 8, 12.
• Change from baseline in hsCRP at Weeks 4, 8, 12.
• Change over time in the mean IBDQ domain and total scores from baseline to Week 12.
• Proportion of subjects with an IBDQ total score of =170 at Week 12.
• Safety and tolerability evaluated by the frequency of AEs, SAEs, AEs leading to discontinuation of study treatment.
• PF-00547659 concentration-time profile.

Exploratory Endpoints
• Change from baseline in Simple Clinical Colitis Activity Index (SCCAI) at Weeks 4, 8, 12.
• Percentage of subjects with a decrease in the SCCAI scores of =3 points at Weeks 4 and 12.

• Percentage of subjects with clinical remission at Weeks 4, 8, and 12 defined as a total SCCAI score of < 2 points.
• Laboratory tests, electrocardiograms (ECGs) and vital signs will be summarized.

Health Outcomes
• Proportion of subjects with a clinically meaningful change in the IBDQ total score (>/= 16 points) at Week 12.
• Changes over time in the European Quality of Life 5 Dimensions questionnaire (EQ 5D)(TM) and EQ 5D visual analog scale (VAS) scores from baseline to Week 12.

Secondary ID(s)

A7281009

2012-002030-37-BE

Source(s) of Monetary Support

Pfizer Inc