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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
84
200 mg sterile liquid vial, administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
200 mg sterile liquid vial, dose level 400 mg administered intravenously, one-hour infusion on Day 1, Week 2, 4, 8, and 12
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.
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.
Time frame: Baseline, Week 14
Maximum Observed Plasma Concentration (Cmax) for Anrukinzumab
Maximum concentration observed during the dosing interval (2 weeks for day 1, 4 weeks for week 12).
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
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
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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
The Kirkland Clinic
Birmingham, Alabama, United States
UAB Hospital
Birmingham, Alabama, United States
UAB Hospital Department of Pharmacy
Birmingham, Alabama, United States
Administrative Offices
Birmingham, Alabama, United States
UAB ACIP
Birmingham, Alabama, United States
Arizona Surgical Center
Phoenix, Arizona, United States
Dedicated Phase I, Inc.
Phoenix, Arizona, United States
AGMG Endoscopy Center
Anaheim, California, United States
Anaheim Clinical Trials, LLC
Anaheim, California, United States
West Coast Radiology Center
Santa Ana, California, United States
...and 66 more locations
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.
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
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.
Time frame: Baseline, Week 2, 4, 8, 12
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)
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.
Time frame: Baseline up to Week 32
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
Neutralizing antibody was not analyzed as no participant had positive ADA samples.
Time frame: 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.
Time frame: Baseline, Week 14