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Trial record 1 of 1 for:    NCT01284062
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Pharmacokinetics/Pharmacodynamics Biomarker Study in Active Ulcerative Colitis Patients

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ClinicalTrials.gov Identifier: NCT01284062
Recruitment Status : Completed
First Posted : January 26, 2011
Results First Posted : November 18, 2014
Last Update Posted : November 18, 2014
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE January 25, 2011
First Posted Date  ICMJE January 26, 2011
Results First Submitted Date  ICMJE November 10, 2014
Results First Posted Date  ICMJE November 18, 2014
Last Update Posted Date November 18, 2014
Study Start Date  ICMJE March 2011
Actual Primary Completion Date April 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 10, 2014)
Fold Change From Baseline in Fecal Calprotectin at Week 14 [ Time Frame: Baseline, Week 14 ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 25, 2011)
Fold Change From Baseline in Fecal Calprotectin at Week 14 [ Time Frame: Week 14 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 10, 2014)
  • Maximum Observed Plasma Concentration (Cmax) for Anrukinzumab [ Time Frame: Pre-dose to end of the dosing interval after Day 1, Week 12 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
  • Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Week 32 ]
    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 ]
  • 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 ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 25, 2011)
  • The PK of anrukinzumab will be characterized from data obtained at pre specified time points up to 32 weeks. The pharmacokinetic parameters AUC, CL and half life will be estimated using a population PK approach. [ Time Frame: Up to Week 32 ]
  • Fold change from baseline in fecal calprotectin at Weeks 2, 4, 8, and 12. [ Time Frame: 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. [ Time Frame: Up to Week 32 ]
  • The frequency of on treatment adverse events, serious adverse events and withdrawals due to adverse events will be summarized. [ Time Frame: Duration of study ]
  • Frequency of ADAs and NAbs, if observed, at all PK timepoints up to 32 weeks. [ Time Frame: Up to Week 32 ]
  • Clinical response rate at Week 14 [ Time Frame: Week 14 ]
Current Other Pre-specified Outcome Measures
 (submitted: November 10, 2014)
  • Clinical Response Rate at Week 14 [ Time Frame: Week 14 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetics/Pharmacodynamics Biomarker Study in Active Ulcerative Colitis Patients
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Colitis, Ulcerative
Intervention  ICMJE
  • 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
  • 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
  • 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
  • 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
Study Arms  ICMJE
  • Experimental: Arm 1
    200 mg PF-05230917, Anrukinzumab active dose level
    Intervention: Biological: Anrukinzumab
  • Experimental: Arm 2
    400 mg PF-05230917, Anrukinzumab active dose level
    Intervention: Biological: Anrukinzumab
  • Experimental: Arm 3
    600 mg PF-05230917, Anrukinzumab active dose level
    Intervention: Biological: Anrukinzumab
  • Placebo Comparator: Arm 4
    Matching placebo - administered at matching dose level 200 mg, 400 mg or 600 mg.
    Intervention: Other: placebo
Publications * Reinisch W, Panés J, Khurana S, Toth G, Hua F, Comer GM, Hinz M, Page K, O'Toole M, Moorehead TM, Zhu H, Sun Y, Cataldi F. Anrukinzumab, an anti-interleukin 13 monoclonal antibody, in active UC: efficacy and safety from a phase IIa randomised multicentre study. Gut. 2015 Jun;64(6):894-900. doi: 10.1136/gutjnl-2014-308337. Epub 2015 Jan 7.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 6, 2013)
84
Original Estimated Enrollment  ICMJE
 (submitted: January 25, 2011)
80
Actual Study Completion Date  ICMJE April 2013
Actual Primary Completion Date April 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Bulgaria,   Canada,   France,   Germany,   Hungary,   Netherlands,   Poland,   Romania,   Spain,   United States
Removed Location Countries Belgium
 
Administrative Information
NCT Number  ICMJE NCT01284062
Other Study ID Numbers  ICMJE B2421003
IMA-638 Anti-IL13 mAb
2010-023762-49 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP