Inflamm Bowel Dis. 2022 Jul 1;28(7):1034-1044. doi: 10.1093/ibd/izab215.

Geert R D'Haens ¹, Walter Reinisch ², Scott D Lee ³, Dino Tarabar ⁴, Edouard Louis ⁵, Maria Klopocka ⁶, Jochen Klaus ⁷, Stefan Schreiber ⁸, Dong Il Park ⁹, Xavier Hébuterne ¹⁰, Peter Nagy ¹¹, Fabio Cataldi ¹², Steven W Martin ¹³, Satyaprakash Nayak ¹³, Anindita Banerjee ¹³, Kenneth J Gorelick ¹⁴, William J Sandborn ¹⁵

Author information

¹Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands.

²Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

³Division of Gastroenterology, University of Washington, Seattle, WA, USA.

⁴Clinic of Gastroenterology and Hepatology, Military Medical Academy, Belgrade, Serbia.

⁵Department of Clinical Sciences, University Hospital Centre Hospitalier Universitaire of Liège, Liège, Belgium.

⁶Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland.

⁷Clinic for Internal Medicine, University Hospital Ulm, Ulm, Germany.

⁸Clinic for Internal Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University of Kiel, Kiel, Germany.

⁹Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul, South Korea.

¹⁰University Côte d'Azur, Centre Hospitalier Universitaire of Nice, Nice, France.

¹¹Shire, a Takeda company, Zug, Switzerland.

¹²Shire, a Takeda company, Lexington, MA, USA.

¹³Pfizer, Cambridge, MA, USA.

¹⁴Zymo Consulting Group, Newtown Square, PA, USA.

¹⁵Medicine, University of California San Diego, La Jolla, CA, USA.

Abstract

Background: Patients with Crohn's disease (CD) experience intestinal inflammation. Ontamalimab (SHP647), a fully human immunoglobulin G2 monoclonal antibody against mucosal addressin cell adhesion molecule-1, is a potential novel CD treatment. OPERA II, a multicenter, open-label, phase 2 extension study, assessed the long-term safety and efficacy of ontamalimab in patients with moderate-to-severe CD.

Methods: Patients had completed 12 weeks of blinded treatment (placebo or ontamalimab at 22.5, 75, or 225 mg subcutaneously) in OPERA (NCT01276509) or had a clinical response to ontamalimab 225 mg in TOSCA (NCT01387594). Participants received ontamalimab at 75 mg every 4 weeks (weeks 0-72), then were followed up every 4 weeks for 24 weeks. One-time dose reduction to 22.5 mg or escalation to 225 mg was permitted at the investigator's discretion. The primary end points were safety and tolerability outcomes. Secondary end points included changes in serum drug and biomarker concentrations. Efficacy end points were exploratory, and used non-responder imputation methods.

Results: Overall, 149/268 patients completed the study. The most common adverse event leading to study discontinuation was CD flare (19.8%). Two patients died; neither death was considered to be drug related. No dose reductions occurred; 157 patients had their dose escalated. Inflammatory biomarker concentrations decreased. Serum ontamalimab levels were consistent with known pharmacokinetics. Remission rates (Harvey-Bradshaw Index [HBI] ≤ 5; baseline, 48.1%; week 72, 37.3%) and response rates (baseline [decrease in Crohn's Disease Activity Index ≥ 70 points], 63.1%; week 72 [decrease in HBI ≥ 3], 42.5%) decreased gradually.

Conclusions: Ontamalimab was well tolerated; treatment responses appeared to be sustained over 72 weeks.ClinicalTrials.gov ID: NCT01298492.