OP20 Results from the STENOVA trial: A Phase 2a, randomized, placebo-controlled, double-blind study to assess the safety, pharmacokinetics (PK), and pharmacodynamics of ontunisertib (AGMB-129) in patients with Fibrostenotic Crohn’s Disease (FSCD)
Abstract
Ontunisertib is an oral GI-restricted ALK5 inhibitor, developed for the treatment of FSCD, which potently blocks signalling of the key pro-fibrotic TGFβ pathway. To date, development of systemic ALK5 inhibitors has been hampered by systemic, particularly cardiac, toxicities. Ontunisertib was designed to have high local GI exposure while avoiding clinically relevant systemic exposure through high first-pass liver metabolism. STENOVA is the first randomized, placebo-controlled clinical trial conducted in FSCD. We report results from the primary analysis in patients having completed the 12-week placebo-controlled treatment period. An open-label treatment extension study is ongoing.
Adults with symptomatic FSCD with at least 1 MRE-confirmed ileal stricture were randomized 1:1:1 to receive ontunisertib 200mg BID, 100mg QD, or placebo (PBO) for 12 weeks. The primary objective was to evaluate safety and tolerability. The evaluation of plasma PK was included as a secondary objective. Exploratory outcomes encompassed PK in ileal and colonic mucosa, change in SES-CD, and change in MRE-based stricture parameters.
The primary analysis included 103 participants (34/34/35 in the 200mg/100mg/PBO groups), of which 92 completed the treatment period. Baseline characteristics were comparable across groups (table). Ontunisertib was generally well tolerated at both doses. The proportion of patients with at least 1 treatment-emergent AE in the 200mg BID, 100mg QD, and PBO groups was 61.8%, 64.7%,…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 103 participants or records.
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