Clinical Trial: Pharmacokinetics/Pharmacodynamics Biomarker Study in Active Ulcerative Colitis Patients

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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 <

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 Summary:
Sponsor: Pfizer

Current Primary Outcome: Fold Change From Baseline in Fecal Calprotectin at Week 14 [ Time Frame: Baseline, Week 14 ]

Original Primary Outcome: Fold Change From Baseline in Fecal Calprotectin at Week 14 [ Time Frame: Week 14 ]

Current Secondary Outcome:

• 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:

• 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 ]

Dates:
Date Received: January 25, 2011
Date Started: March 2011
Date Completion:
Last Updated: November 10, 2014
Last Verified: November 2014