PMID- 33599720 OWN - NLM STAT- MEDLINE DCOM- 20211206 LR - 20211214 IS - 1876-4479 (Electronic) IS - 1873-9946 (Print) IS - 1873-9946 (Linking) VI - 15 IP - 6 DP - 2021 Jun 22 TI - Long-term Safety and Efficacy of the Anti-MAdCAM-1 Monoclonal Antibody Ontamalimab [SHP647] for the Treatment of Ulcerative Colitis: The Open-label Study TURANDOT II. PG - 938-949 LID - 10.1093/ecco-jcc/jjab023 [doi] AB - BACKGROUND AND AIMS: Ontamalimab, a fully-human monoclonal antibody targeting MAdCAM-1, induced remission in patients with moderate-to-severe ulcerative colitis [UC] in the TURANDOT study. We aimed to assess long-term safety, tolerability, and efficacy of ontamalimab in TURANDOT II. METHODS: TURANDOT II was a phase 2, multicentre, open-label [OL] study in patients with moderate-to-severe UC who completed TURANDOT on placebo or ontamalimab (NCT01771809). Patients were randomised to 75 mg or 225 mg ontamalimab every 4 weeks for 72 weeks [OL1]. The dosage could be increased to 225 mg from Week 8 at the investigator's discretion. All patients then received 75 mg every 4 weeks for 72 weeks [OL2], followed by 6-month safety follow-up. The primary objective was safety, measured by adverse events [AEs], serious AEs [SAEs], and AEs leading to withdrawal. Mucosal healing [MH; centrally read endoscopy] was assessed. RESULTS: Of 330 patients, 180 completed OL1; 94 escalated to 225 mg; 127 completed OL2. Overall, 36.1% experienced drug-related AEs. The most common SAE [10.0%] was worsening/ongoing UC; 5.5% of patients had serious infections, the most common being gastroenteritis [0.9%]. One death and four cancers [all unrelated to ontamalimab] occurred. No PML [progressive multifocal leukoencephalopathy]/lymphoproliferative disorders occurred. Geometric mean high-sensitivity C-reactive protein [hsCRP] and faecal calprotectin decreased across OL1 in both dose groups. The proportion of patients assigned to placebo in TURANDOT achieving MH increased from 8.8% [6/68] at baseline to 35.3% at Week 16 [24/68; non-responder imputation]. The corresponding increase in the ontamalimab group was from 23.3% [61/262] to 26.7% [70/262]. CONCLUSIONS: Ontamalimab was well tolerated up to 144 weeks in patients with moderate-to-severe UC, with good safety and efficacy. CI - (c) The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn's and Colitis Organisation. FAU - Reinisch, Walter AU - Reinisch W AD - Department of Internal Medicine, Medical University of Vienna, Vienna, Austria. FAU - Sandborn, William J AU - Sandborn WJ AD - Department of Medicine, University of California San Diego, La Jolla, CA, USA. FAU - Danese, Silvio AU - Danese S AD - Inflammatory Bowel Diseases Center, Humanitas University, Milan, Italy. FAU - Hebuterne, Xavier AU - Hebuterne X AD - University of Nice Sophia Antipolis, CHU of Nice, Nice, France. FAU - Klopocka, Maria AU - Klopocka M AD - Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland. FAU - Tarabar, Dino AU - Tarabar D AD - Clinic of Gastroenterology and Hepatology, Military Medical Academy, Belgrade, Serbia. FAU - Vanasek, Tomas AU - Vanasek T AD - Faculty of Medicine, Charles University Hospital, Hradec Kralove, Czech Republic. FAU - Gregus, Milos AU - Gregus M AD - Gastroenterology Centre, Nitra, Slovakia. FAU - Hellstern, Paul A AU - Hellstern PA AD - Gastroenterology, Nature Coast Clinical Research, Inverness, FL, USA. FAU - Kim, Joo Sung AU - Kim JS AD - Seoul National University College of Medicine, Seoul, South Korea. FAU - Sparrow, Miles P AU - Sparrow MP AD - Inflammatory Bowel Disease Clinic, Alfred Hospital, Melbourne, VIC, Australia. FAU - Gorelick, Kenneth J AU - Gorelick KJ AD - Zymo Consulting Group, Newtown Square, PA, USA. FAU - Hoy, Michael AU - Hoy M AD - Shire, a Takeda company, Lexington, MA, USA. FAU - Goetsch, Martina AU - Goetsch M AD - Shire, a Takeda company, Zug, Switzerland. FAU - Bliss, Caleb AU - Bliss C AD - Shire, a Takeda company, Lexington, MA, USA. FAU - Gupta, Charu AU - Gupta C AD - Cytel Inc., Cambridge, MA, USA. FAU - Cataldi, Fabio AU - Cataldi F AD - Shire, a Takeda company, Lexington, MA, USA. FAU - Vermeire, Severine AU - Vermeire S AD - Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PL - England TA - J Crohns Colitis JT - Journal of Crohn's & colitis JID - 101318676 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Cell Adhesion Molecules) RN - 0 (Gastrointestinal Agents) RN - 0 (Leukocyte L1 Antigen Complex) RN - 0 (MADCAM1 protein, human) RN - 0 (Mucoproteins) RN - 6LGI7RV4PB (ontamalimab) RN - 9007-41-4 (C-Reactive Protein) SB - IM MH - Adult MH - *Antibodies, Monoclonal, Humanized/administration & dosage/adverse effects MH - C-Reactive Protein/analysis MH - Cell Adhesion Molecules/*antagonists & inhibitors MH - *Colitis, Ulcerative/diagnosis/drug therapy/immunology MH - Dose-Response Relationship, Immunologic MH - *Drug Monitoring/methods/statistics & numerical data MH - Endoscopy, Gastrointestinal/methods/statistics & numerical data MH - Female MH - Gastrointestinal Agents/administration & dosage/adverse effects MH - Humans MH - Leukocyte L1 Antigen Complex/analysis MH - Male MH - Mucoproteins/*antagonists & inhibitors MH - Treatment Outcome PMC - PMC8218706 OTO - NOTNLM OT - MAdCAM-1 OT - Ulcerative colitis OT - phase 2 EDAT- 2021/02/19 06:00 MHDA- 2021/12/15 06:00 PMCR- 2021/02/18 CRDT- 2021/02/18 12:14 PHST- 2021/02/19 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/02/18 12:14 [entrez] PHST- 2021/02/18 00:00 [pmc-release] AID - 6144575 [pii] AID - jjab023 [pii] AID - 10.1093/ecco-jcc/jjab023 [doi] PST - ppublish SO - J Crohns Colitis. 2021 Jun 22;15(6):938-949. doi: 10.1093/ecco-jcc/jjab023.