A study to evaluate the safety and how anrukinzumab (IMA-638) works in the body for patients with Ulcerative Colitis

• Register: EUCTR
• Last refreshed on: 11 November 2013
• Main ID: EUCTR2010-023762-49-PL
• Date of registration: 05/07/2011
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc., 235 East 42nd Street, New York, NY 10017
• Public title: A study to evaluate the safety and how anrukinzumab (IMA-638) works in the body for patients with Ulcerative Colitis
• Scientific title: A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, SPONSOR UNBLINDED, PLACEBO-CONTROLLED, MULTIPLE DOSE STUDY TO EVALUATE THE PHARMACODYNAMICS, PHARMACOKINETICS AND SAFETY OF ANRUKINZUMAB IN PATIENTS WITH ACTIVE ULCERATIVE COLITIS - IMA-638 Ulcerative Colitis Study
• Date of first enrolment: 06/01/2012
• Target sample size: 80
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-023762-49
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no 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

Countries of recruitment

Austria, Belgium, Bulgaria, Canada, France, Germany, Hungary, Netherlands, Poland, Romania, Spain, 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 a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
2. Patients are willing and able to participate in the study, complete patient assessments, attend scheduled clinic visits, and comply with all protocol requirements as evidenced by written informed consent.
3. Male and/or female patients between the ages of =18 and =65 years at the time of informed consent.
4. Positive histological diagnosis of UC. A biopsy report must be available in the patient’s source documentation. In addition, a report documenting disease duration and extent of disease (eg, proctosigmoiditis, left sided colitis and pancolitis) based upon prior colonoscopy must also be available in source documentation. A colonoscopy with biopsy will need to be performed if this documentation is not available.
5. Diagnosis of active UC determined within the screening period as defined by a Mayo score =4 and <10 points and with an endoscopic sub score (based upon flexible sigmoidoscopy) of =2 points.
6. Fecal calprotectin =100 mg/kg within the screening period. The screening fecal calprotectin may be repeated once during the screening period with results available and reviewed prior to the baseline visit.
7. Subjects that are taking 5 ASA prior to screening must be on a stable dose for at least two (2) weeks prior to their first screening visit.
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.
• 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 patient'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 informed consent form through the conclusion of patient participation). Contraceptive methods considered acceptable for use in this study include:
• Established use of oral, injected, transdermal or implanted hormonal methods of contraception.
• Double barrier contraception: use of condom and occlusive diaphragm (cap 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.
10. 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 for the duration of the study (defined as the time of the signing of the informed consent form through the conclusion of patient participation). Highly effective methods of contraception include properly used spermicidal condom.
•
Exclusion criteria:
Patients presenting with any of the following will not be included in the study:
1. Indeterminate colitis, ischemic colitis, fulminant colitis and Crohn’s disease.
2. UC confined to proctitis or disease confined to the rectum only.
3. Any previous colonic or likely to require colonic surgery within the duration of the study. Any other abdominal surgery within 12 weeks or likely to require abdominal surgery within the duration of the study.
4. 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. Documentation of the official reading must be located and available in the source documentation.).
5. 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. Patients 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 (GFT GIT) and T SPOT® TB test.
• A positive Mantoux tuberculin skin test is defined as =5 mm of induration (or as defined by country specific or local standards) at 48 72 hours without consideration of prior Bacillus Calmette Guérin (BCG) vaccination. Documentation of the dose and product used for the Mantoux tuberculin test as well as the official test reading must be obtained and available in the patient's study file.
• An IGRA is preferred for patients with a prior Bacillus Calmette Guérin (BCG) vaccination (to be tested by a site’s local lab). Documentation of the IGRA product used and the test result must be in the patient’s source documentation.
6. Active enteric infections, pseudomembranous colitis, salmonella, shigella campylobacter or other GI bacterial, fungal or parasitic infection or known active invasive fungal infections such as histoplasmosis (stool culture and sensitivity, ova & parasites as well as Clostridium difficile toxins A and B may be tested by the site’s local lab). Any underlying disease that could predispose the patient to infections or history of serious infection (requiring parenteral antibiotic and/or hospitalization) within 4 weeks before the baseline visit. Pyoderma gangrenosum is allowed.
7. Preexisting demyelinating disorder including multiple sclerosis or new onset seizures, unexplained sensory, motor, or cognitive/behavioral or neurological deficits.
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 acute or unstable clinical condition (eg, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, immunologic [eg, Felty syndrome], or infectious illness) that, in the investigator’s judgment, will substantially increase the risk to the patient 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)

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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Ulcerative Colitis
MedDRA version: 14.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 10017947 - Gastrointestinal disorders

Intervention(s)

Product Name: Not Applicable
Product Code: PF-05230917
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not Applicable
Current Sponsor code: PF-05230917
Other descriptive name: Not applicable
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): • Fold change from baseline in fecal calprotectin at Week 14.

Note: Fold change is defined as (post-treatment measurement)/(baseline measurement), which is related to percent change from baseline by the following equation: Percent change from baseline = 100% x (fold change-1).

Secondary Objective: • Characterization of the PK profile and total IL 13 of three multiple escalating IV doses of anrukinzumab versus placebo.
• Determination of the safety, tolerability and immunogenicity of anrukinzumab in patients with active UC.

Timepoint(s) of evaluation of this end point: Week 14

Main Objective: The primary objective is to characterize the change in the Pharmacodynamic (PD) biomarker, fecal calprotectin, during treatment with anrukinzumab.

Secondary Outcome(s)

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

Secondary end point(s): Pharmacokinetic Endpoints
• The PK of anrukinzumab will be characterized from data obtained at pre specified time points up to 32 weeks. The pharmacokinetic parameters including AUC and half life will be estimated using noncompartmental analysis and additional parameters may be estimated using population PK analysis.
Pharmacodynamic Endpoints
• Fold change from baseline in fecal calprotectin at Weeks 2, 4, 8, and 12.
• Total IL 13 (free IL 13 and IL 13 complexed with anrukinzumab) measured at pre specified time points up to 32 weeks.
Safety Endpoints
• The frequency of on treatment adverse events, serious adverse events and withdrawals due to adverse events will be summarized.
• Frequency of ADAs and Nabs, if observed, at pre specified timepoints up to 32 weeks.

Secondary ID(s)

2010-023762-49-ES

B2421003

NCT01284062

Source(s) of Monetary Support

Pfizer Inc