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.
Adult
Antibodies, Monoclonal, Humanized
/ administration & dosage
C-Reactive Protein
/ analysis
Cell Adhesion Molecules
/ antagonists & inhibitors
Colitis, Ulcerative
/ diagnosis
Dose-Response Relationship, Immunologic
Drug Monitoring
/ methods
Endoscopy, Gastrointestinal
/ methods
Female
Gastrointestinal Agents
/ administration & dosage
Humans
Leukocyte L1 Antigen Complex
/ analysis
Male
Mucoproteins
/ antagonists & inhibitors
Treatment Outcome
MAdCAM-1
Ulcerative colitis
phase 2
Journal
Journal of Crohn's & colitis
ISSN: 1876-4479
Titre abrégé: J Crohns Colitis
Pays: England
ID NLM: 101318676
Informations de publication
Date de publication:
22 Jun 2021
22 Jun 2021
Historique:
pubmed:
19
2
2021
medline:
15
12
2021
entrez:
18
2
2021
Statut:
ppublish
Résumé
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. 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. 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]. Ontamalimab was well tolerated up to 144 weeks in patients with moderate-to-severe UC, with good safety and efficacy.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
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
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
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
CONCLUSIONS
Ontamalimab was well tolerated up to 144 weeks in patients with moderate-to-severe UC, with good safety and efficacy.
Identifiants
pubmed: 33599720
pii: 6144575
doi: 10.1093/ecco-jcc/jjab023
pmc: PMC8218706
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Cell Adhesion Molecules
0
Gastrointestinal Agents
0
Leukocyte L1 Antigen Complex
0
MADCAM1 protein, human
0
Mucoproteins
0
ontamalimab
6LGI7RV4PB
C-Reactive Protein
9007-41-4
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
938-949Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.
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