Eldelumab [anti-interferon-γ-inducible protein-10 antibody] Induction Therapy for Active Crohn's Disease: a Randomised, Double-blind, Placebo-controlled Phase IIa Study.
OBJECTIVE
This 11-week Phase IIa induction study evaluated the efficacy and safety of eldelumab in patients with active Crohn's disease.


METHODS
Adults with Crohn's Disease Activity Index 220-450 were randomised 1:1:1 to placebo or eldelumab 10 or 20 mg/kg intravenously on Days 1 and 8, and alternate weeks thereafter. All patients underwent ileocolonoscopy at baseline. Patients with active inflammation according to the Simplified Endoscopic Score for Crohn's Disease criteria [the originally planned endoscopy cohort] underwent another ileocolonoscopy at Week 11 at the investigator's discretion. All ileocolonoscopies were centrally read. The primary objective was identification of the eldelumab target exposure for induction of remission [absolute Crohn's Disease Activity Index score < 150]. Rates of clinical response [reduction of ≥ 100 from baseline or absolute score < 150 Crohn's Disease Activity Index], remission, and endoscopic improvements were also assessed.


RESULTS
A total of 121 patients were randomised. The eldelumab exposure-remission relationship was not significant at Week 11. Numerically higher remission and response rates were reported with eldelumab 20 mg/kg [29.3% and 41.5%, respectively] and 10 mg/kg [22.5% and 47.5%] versus placebo [20.0% and 35.0%]. A higher proportion of patients with a baseline Simplified Endoscopic Score for Crohn's Disease > 2 who received eldelumab achieved a 50% improvement in score and greater reductions from baseline endoscopy scores overall versus placebo. Adverse events were comparable across treatment groups.


CONCLUSIONS
No exposure-remission relationship was seen with eldelumab. Eldelumab induction treatment demonstrated trends towards clinical and endoscopic efficacy. Safety was consistent with that reported previously. ClinicalTrials.gov identifier: NCT01466374.
Inflammatory Bowel Disease Center, University of California San Diego, La Jolla, CA, USA.
William J
WJ
Sandborn
Department of Gastroenterology, Catholic University Leuven, Belgium.
Paul
P
Rutgeerts
Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Jean-Frédéric
JF
Colombel
Division of Gastroenterology, University of Calgary, Calgary, AB, Canada.
Subrata
S
Ghosh
NZOZ Vivamed, Zespól Lekarzy Specjalistów, Warszawa, Poland.
Robert
R
Petryka
Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Bruce E
BE
Sands
Bristol-Myers Squibb, Lawrenceville, NJ, USA.
Pranab
P
Mitra
Bristol-Myers Squibb, Lawrenceville, NJ, USA.
Allison
A
Luo
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003113:Colonoscopy; D003424:Crohn Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012720:Severity of Illness Index; D055815:Young Adult
D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; C000613134:eldelumab
Anti-interferon-γ-inducible protein-10 antibody; Crohn’s disease; inflammatory bowel disease