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Pharmacokinetics/Pharmacodynamics Biomarker Study in Active Ulcerative Colitis Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01284062
First received: January 25, 2011
Last updated: November 10, 2014
Last verified: November 2014
  Purpose

This study represents the first investigation of anrukinzumab in patients with active ulcerative colitis (UC) and will evaluate proof of mechanism by changes in the mechanism based biomarker (YKL 40) and pharmacodynamic biomarkers (fecal calprotectin, lactoferrin and hs-CRP). It will provide further assessment of the safety, tolerability, and pharmacokinetics (PK) by administration of multiple intravenous (IV) doses of anrukinzumab.


Condition Intervention Phase
Colitis, Ulcerative
Biological: Anrukinzumab
Other: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2a, Randomized, Double-blind, Sponsor Unblinded, Placebo-controlled, Multiple Dose Study To Evaluate The Pharmacodynamics, Pharmacokinetics And Safety Of Anrukinzumab In Subjects With Active Ulcerative Colitis

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Fold Change From Baseline in Fecal Calprotectin at Week 14 [ Time Frame: Baseline, Week 14 ] [ Designated as safety issue: No ]
    The fold change from baseline in fecal calprotectin at Week 14, is the ratio of the measurement of fecal calprotectin at Week 14 to baseline measurement; this was calculated as the change from baseline in natural log transformed fecal calprotectin at Week 14.


Secondary Outcome Measures:
  • Maximum Observed Plasma Concentration (Cmax) for Anrukinzumab [ Time Frame: Pre-dose to end of the dosing interval after Day 1, Week 12 ] [ Designated as safety issue: No ]
    Maximum concentration observed during the dosing interval (2 weeks for day 1, 4 weeks for week 12).

  • Minimum Observed Plasma Trough Concentration (Cmin) for Anrukinzumab [ Time Frame: Pre-dose to end of the dosing interval after Day 1, Week 12 ] [ Designated as safety issue: No ]
    Lowest concentration observed during the dosing interval (2 weeks for day 1, 4 weeks for week 12).

  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Anrukinzumab [ Time Frame: Pre-dose, within 1 hour post-end of infusion on Day 1; Day 2, 4, 7, pre-dose on Week 2 ] [ Designated as safety issue: No ]
    Area under the plasma concentration curve from time zero to end of dosing interval (2 weeks) was reported.

  • Plasma Decay Half-Life (t1/2) for Anrukinzumab [ Time Frame: Within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • Systemic Clearance (CL) for Anrukinzumab [ Time Frame: Pre-dose, within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 ] [ Designated as safety issue: No ]
    CL is a quantitative measure of the rate at which a drug substance is removed from the body.

  • Volume of Distribution (Vz) for Anrukinzumab [ Time Frame: Pre-dose, within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 ] [ Designated as safety issue: No ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

  • Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 12 [ Time Frame: Baseline, Week 2, 4, 8, 12 ] [ Designated as safety issue: No ]
    The fold change from baseline in fecal calprotectin at post-baseline visit, is the ratio of the measurement of fecal calprotectin at post-baseline visit to baseline measurement; this was calculated as the change from baseline in natural log transformed fecal calprotectin at post-baseline visit.

  • Total Interleukin-13 (IL-13) Level [ Time Frame: Baseline, Day 2, 4, 7, Week 2, 4, 8, 12, 14, 16, 20, 24, 28, 32 ] [ Designated as safety issue: No ]
  • Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Week 32 ] [ Designated as safety issue: Yes ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 32 that were absent before treatment or that worsened relative to pretreatment state. All causality AEs included SAEs as well as non-serious AEs, without regard to relationship to the study drug, which occurred during the trial.

  • Number of Participants Who Discontinued From the Study Due to Adverse Events [ Time Frame: Baseline up to Week 32 ] [ Designated as safety issue: Yes ]
  • Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody [ Time Frame: Day 1, Week 4, 8, 12, 14, 16, 20, 24, 28, 32 ] [ Designated as safety issue: Yes ]
    Neutralizing antibody was not analyzed as no participant had positive ADA samples.

  • Number of Participants With Change From Baseline in Endoscopic Subscore at Week 14 [ Time Frame: Baseline, Week 14 ] [ Designated as safety issue: No ]
    Mayo score is used to measure the disease activity of ulcerative colitis. Endoscopy or flexible sigmoidoscopy is a sub score of Mayo score. The score for endoscopic subscore ranges from 0 to 3, where higher score indicates more severe disease activity. Participant's score for endoscopy or flexible sigmoidoscopy at Week 14 was specified as improved (decrease), no change and worsened (increase) compared to their baseline score.


Other Outcome Measures:
  • Clinical Response Rate at Week 14 [ Time Frame: Week 14 ] [ Designated as safety issue: No ]
    Clinical response rate is defined as percentage of participants with at least 3 point decrease from baseline in total Mayo score with at least 30% change along with 1 point decrease from baseline or absolute score of 0 or 1 in rectal bleeding. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, findings on flexible sigmoidoscopy [endoscopy] and physician's global assessment), each subscore is graded from 0 to 3 with the higher score indicating more severe disease activity.

  • Clinical Remission Rate at Week 14 [ Time Frame: Week 14 ] [ Designated as safety issue: No ]
    Clinical remission rate is defined as percentage of participants with a total Mayo score less than or equal to 2, with no individual subscore greater than 1 at post baseline visit. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, findings on flexible sigmoidoscopy and physician's global assessment), each subscore is graded from 0 to 3 with the higher score indicating more severe disease activity.

  • Change From Baseline in Total Mayo Score at Week 14 [ Time Frame: Baseline, Week 14 ] [ Designated as safety issue: No ]
    The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, findings on flexible sigmoidoscopy [endoscopy] and physician's global assessment), each subscore is graded from 0 to 3 with the higher score indicating more severe disease activity.

  • Number of Participants With Change From Baseline in Stool Frequency at Week 14 [ Time Frame: Baseline, Week 14 ] [ Designated as safety issue: No ]
    Stool frequency is a sub score of Mayo score used to measure the disease activity of ulcerative colitis. The score for stool frequency ranges from 0 to 3, where higher score indicates more severe disease activity. Participant's score for stool frequency at Week 14 was specified as improved (decrease), no change and worsened (increase) compared to their baseline score.

  • Number of Participants With Change From Baseline in Rectal Bleeding at Week 14 [ Time Frame: Baseline, Week 14 ] [ Designated as safety issue: No ]
    Mayo score is used to measure the disease activity of ulcerative colitis. Rectal bleeding is a sub score of Mayo score. The score for rectal bleeding ranges from 0 to 3, where higher score indicates more severe disease activity. Participant's score for rectal bleeding at Week 14 was specified as improved (decrease), no change and worsened (increase) compared to their baseline score.


Enrollment: 84
Study Start Date: March 2011
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
200 mg PF-05230917, Anrukinzumab active dose level
Biological: Anrukinzumab
200 mg sterile liquid vial, administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Other Name: PF-05230917
Experimental: Arm 2
400 mg PF-05230917, Anrukinzumab active dose level
Biological: Anrukinzumab
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Other Name: PF-05230917
Experimental: Arm 3
600 mg PF-05230917, Anrukinzumab active dose level
Biological: Anrukinzumab
200 mg sterile liquid vial, dose level 600 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12 Note: dosing in the 600 mg arm will be delayed until the safety of the 200 mg and 400 mg arms has been reviewed.
Other Name: PF-05230917
Placebo Comparator: Arm 4
Matching placebo - administered at matching dose level 200 mg, 400 mg or 600 mg.
Other: placebo
200 mg liquid sterile vial, administered at matching dose level 200 mg, 400 mg or 600 mg intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
Other Name: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or Female, Age >=18 and <=65 years
  • Active ulcerative colitis (UC) beyond the rectum based upon Mayo Score
  • women of childbearing potential with highly effective method of contraception

Exclusion Criteria:

  • Indeterminate disease status, Crohn's disease, ischemic colitis, positive HIV, positive or history of tuberculosis infection, active enteric infections, transplant organ recipient, concomitant steroids, immunosuppressives or anti-TNFs.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01284062

  Show 76 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01284062     History of Changes
Other Study ID Numbers: B2421003, IMA-638 Anti-IL13 mAb, 2010-023762-49
Study First Received: January 25, 2011
Results First Received: November 10, 2014
Last Updated: November 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Active Ulcerative Colitis
Phase 2A
Double-blind
Randomized
PK/PD Biomarker Study

Additional relevant MeSH terms:
Colitis
Colitis, Ulcerative
Ulcer
Colonic Diseases
Digestive System Diseases
Gastroenteritis
Gastrointestinal Diseases
Inflammatory Bowel Diseases
Intestinal Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on November 20, 2014