Pharmacokinetics/Pharmacodynamics Biomarker Study in Active Ulcerative Colitis Patients

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Colitis, Ulcerative

Intervention / Treatment
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* Biological: Anrukinzumab
* Biological: Anrukinzumab
* Biological: Anrukinzumab
* Other: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>200 mg PF-05230917, Anrukinzumab active dose level | Biological: Anrukinzumab<br>* 200 mg sterile liquid vial, administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12<br>* Other names: PF-05230917;|
| Experimental: Arm 2<br>400 mg PF-05230917, Anrukinzumab active dose level | Biological: Anrukinzumab<br>* 200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12<br>* Other names: PF-05230917;|
| Experimental: Arm 3<br>600 mg PF-05230917, Anrukinzumab active dose level | Biological: Anrukinzumab<br>* 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.<br>* Other names: PF-05230917;|
| Placebo Comparator: Arm 4<br>Matching placebo - administered at matching dose level 200 mg, 400 mg or 600 mg. | Other: placebo<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fold Change From Baseline in Fecal Calprotectin at 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. | Baseline, Week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) for Anrukinzumab | Maximum concentration observed during the dosing interval (2 weeks for day 1, 4 weeks for week 12). | Pre-dose to end of the dosing interval after Day 1, Week 12 | 
| Minimum Observed Plasma Trough Concentration (Cmin) for Anrukinzumab | Lowest concentration observed during the dosing interval (2 weeks for day 1, 4 weeks for week 12). | Pre-dose to end of the dosing interval after Day 1, Week 12 | 
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Anrukinzumab | Area under the plasma concentration curve from time zero to end of dosing interval (2 weeks) was reported. | Pre-dose, within 1 hour post-end of infusion on Day 1; Day 2, 4, 7, pre-dose on Week 2 | 
| Plasma Decay Half-Life (t1/2) for Anrukinzumab | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 | 
| Systemic Clearance (CL) for Anrukinzumab | CL is a quantitative measure of the rate at which a drug substance is removed from the body. | 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 (Vz) for Anrukinzumab | 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. | Pre-dose, within 1 hour post-end of infusion on Week 12; Week 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 | 
| Fold Change From Baseline in Fecal Calprotectin at Week 2, 4, 8 and 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. | Baseline, Week 2, 4, 8, 12 | 
| Total Interleukin-13 (IL-13) Level |  | 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) | 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. | Baseline up to Week 32 | 
| Number of Participants Who Discontinued From the Study Due to Adverse Events |  | Baseline up to Week 32 | 
| Number of Participants With Anti-drug Antibody (ADA) and Neutralizing Antibody | Neutralizing antibody was not analyzed as no participant had positive ADA samples. | Day 1, Week 4, 8, 12, 14, 16, 20, 24, 28, 32 | 
| Number of Participants With Change From Baseline in Endoscopic Subscore at 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. | Baseline, Week 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Active Ulcerative Colitis, Phase 2A, Double-blind, Randomized, PK/PD Biomarker Study