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.

Abstract

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.

• Authors: Walter Reinisch, William J Sandborn, Silvio Danese, Xavier Hébuterne, Maria Kłopocka, Dino Tarabar, Tomáš Vaňásek, Miloš Greguš, Paul A Hellstern, Joo Sung Kim, Miles P Sparrow, Kenneth J Gorelick, Michael Hoy, Martina Goetsch, Caleb Bliss, Charu Gupta, Fabio Cataldi, Séverine Vermeire
• Journal: Journal of Crohn's & colitis (J Crohns Colitis) Vol. 15 Issue 6 Pg. 938-949 (Jun 22 2021) ISSN: 1876-4479 [Electronic] England
• PMID: 33599720 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.

Chemical References

• Antibodies, Monoclonal, Humanized
• Cell Adhesion Molecules
• Gastrointestinal Agents
• Leukocyte L1 Antigen Complex
• MADCAM1 protein, human
• Mucoproteins
• ontamalimab
• C-Reactive Protein

Topics

• Adult
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects)
• C-Reactive Protein (analysis)
• Cell Adhesion Molecules (antagonists & inhibitors)
• Colitis, Ulcerative (diagnosis, drug therapy, immunology)
• Dose-Response Relationship, Immunologic
• Drug Monitoring (methods, statistics & numerical data)
• Endoscopy, Gastrointestinal (methods, statistics & numerical data)
• Female
• Gastrointestinal Agents (administration & dosage, adverse effects)
• Humans
• Leukocyte L1 Antigen Complex (analysis)
• Male
• Mucoproteins (antagonists & inhibitors)
• Treatment Outcome