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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

W. Reinisch, WJ. Sandborn, S. Danese, X. Hébuterne, M. Kłopocka, D. Tarabar, T. Vaňásek, M. Greguš, PA. Hellstern, JS. Kim, MP. Sparrow, KJ. Gorelick, M. Hoy, M. Goetsch, C. Bliss, C. Gupta, F. Cataldi, S. Vermeire

. 2021 ; 15 (6) : 938-949. [pub] 2021Jun22

Language English Country Great Britain

Document type Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial

Persistent link   https://www.medvik.cz/link/bmc22004193

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.

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$a BACKGROUND AND AIMS: Ontamalimab, a fully-human monoclonal antibody targeting MAdCAM-1, induced remission in patients with moderate-to-severe ulcerative colitis [UC] in the TURANDOT study. We aimed to assess long-term safety, tolerability, and efficacy of ontamalimab in TURANDOT II. METHODS: TURANDOT II was a phase 2, multicentre, open-label [OL] study in patients with moderate-to-severe UC who completed TURANDOT on placebo or ontamalimab (NCT01771809). Patients were randomised to 75 mg or 225 mg ontamalimab every 4 weeks for 72 weeks [OL1]. The dosage could be increased to 225 mg from Week 8 at the investigator's discretion. All patients then received 75 mg every 4 weeks for 72 weeks [OL2], followed by 6-month safety follow-up. The primary objective was safety, measured by adverse events [AEs], serious AEs [SAEs], and AEs leading to withdrawal. Mucosal healing [MH; centrally read endoscopy] was assessed. RESULTS: Of 330 patients, 180 completed OL1; 94 escalated to 225 mg; 127 completed OL2. Overall, 36.1% experienced drug-related AEs. The most common SAE [10.0%] was worsening/ongoing UC; 5.5% of patients had serious infections, the most common being gastroenteritis [0.9%]. One death and four cancers [all unrelated to ontamalimab] occurred. No PML [progressive multifocal leukoencephalopathy]/lymphoproliferative disorders occurred. Geometric mean high-sensitivity C-reactive protein [hsCRP] and faecal calprotectin decreased across OL1 in both dose groups. The proportion of patients assigned to placebo in TURANDOT achieving MH increased from 8.8% [6/68] at baseline to 35.3% at Week 16 [24/68; non-responder imputation]. The corresponding increase in the ontamalimab group was from 23.3% [61/262] to 26.7% [70/262]. CONCLUSIONS: Ontamalimab was well tolerated up to 144 weeks in patients with moderate-to-severe UC, with good safety and efficacy.
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$a Sandborn, William J $u Department of Medicine, University of California San Diego, La Jolla, CA, USA
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$a Danese, Silvio $u Inflammatory Bowel Diseases Center, Humanitas University, Milan, Italy
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$a Hébuterne, Xavier $u University of Nice Sophia Antipolis, CHU of Nice, Nice, France
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$a Kłopocka, Maria $u Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland
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$a Tarabar, Dino $u Clinic of Gastroenterology and Hepatology, Military Medical Academy, Belgrade, Serbia
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$a Vaňásek, Tomáš $u Faculty of Medicine, Charles University Hospital, Hradec Králové, Czech Republic
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$a Greguš, Miloš $u Gastroenterology Centre, Nitra, Slovakia
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$a Hellstern, Paul A $u Gastroenterology, Nature Coast Clinical Research, Inverness, FL, USA
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$a Kim, Joo Sung $u Seoul National University College of Medicine, Seoul, South Korea
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$a Sparrow, Miles P $u Inflammatory Bowel Disease Clinic, Alfred Hospital, Melbourne, VIC, Australia
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$a Gorelick, Kenneth J $u Zymo Consulting Group, Newtown Square, PA, USA
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$a Hoy, Michael $u Shire, a Takeda company, Lexington, MA, USA
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$a Cataldi, Fabio $u Shire, a Takeda company, Lexington, MA, USA
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