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Completed

NCT Number: NCT01284062

Pharmacokinetics/Pharmacodynamics Biomarker Study in Active Ulcerative Colitis Patients

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.

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Key information

Conditions

Colitis, Ulcerative Colitis Colonic Diseases Digestive System Diseases Gastroenteritis Gastrointestinal Diseases Inflammatory Bowel Diseases Intestinal Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Krankenhaus der Elisabethinen Linz GmbH, Linz, Austria

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Anrukinzumab

Biological

200 mg sterile liquid vial, administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12

Other names: PF-05230917

Placebo

Other

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

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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).

  2. 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).

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Total Interleukin-13 (IL-13) Level

    Time frame: Baseline, Day 2, 4, 7, Week 2, 4, 8, 12, 14, 16, 20, 24, 28, 32

  9. 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.

  10. Number of Participants Who Discontinued From the Study Due to Adverse Events

    Time frame: Baseline up to Week 32

  11. 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.

  12. 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.

Other outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study 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

Important dates

Study start
2011
Primary completion
2013
Study completion
2013
First posted
Jan 26, 2011
Registry last updated
Nov 18, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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