P998 Phase 2 basket design study evaluating the efficacy and safety of an anti-TL1A antibody (TEV-48574) in moderate to severe ulcerative colitis or Crohn's Disease (RELIEVE UCCD)

Abstract

Abstract Background TEV-48574 is a human antibody that targets tumor necrosis factor (TNF)-like ligand 1A, also known as TNF superfamily member 15 (TNFSF15). TEV-48574 is being evaluated in the first basket design trial in IBD. The basket design is uniquely suited for the efficient assessment of TEV-48574 as evidence suggests that TL1A signaling plays a key role in both ulcerative colitis (UC) and Crohn’s disease (CD). TL1A signaling is not a primary driver but an amplifier of inflammation; thus, targeting TL1A should mitigate excessive immune responses while leaving baseline immunity intact. Originating in oncology trials, the basket trial design has emerged as a new efficient approach for testing treatment efficacy in different disease indications with potentially common molecular mechanisms. The basket design approach allows the evaluation of multiple indications in a single study design that provides adequate support for initiation of confirmatory studies. Additionally, the basket design allows for shared sites and institutional review boards, data collection and analyses under consistent conditions. Herein, we describe the phase 2b basket trial evaluating TEV-48574 in UC and CD (clinicaltrials.gov NCT05499130), currently ongoing along with a long-term extension study (LTE)(NCT05668013). Methods In this double-blind placebo-controlled global study, TEV-48574 or placebo is administered subcutaneously to adults (n = 240) diagnosed with moderate-to-severe IBD (UC (n = 120) or CD (n = 120)). Patients who meet pre-specified inclusion/exclusion criteria are randomized to either one of two TEV-48574 dose regimens or placebo in a 1:1:1 ratio (stratified by diagnosis (UC or CD) and previous exposure to advanced IBD therapy(biologics and small molecules)) for 14 weeks. Patients who complete the 14-week induction period have the option to enter the LTE, consisting of a 44-week maintenance period for responders and a re-induction period for non-responders. Primary efficacy endpoints are induction of clinical remission (a modified Mayo Score of ≤2 points for UC), and endoscopic response (a reduction in Simple Endoscopic Score for Crohn's Disease (SES-CD) of ≥ 50% from baseline) for CD, at week 14. A Bayesian approach will be used to compute posterior probabilities for the response endpoints within each indication. Additional endpoints include safety assessments, measures of clinical response, biomarkers, pharmacokinetics, and immunogenicity. Results Conclusion TEV-48574 is a potential novel treatment option for patients with UC and CD that may have dual antifibrotic and anti-inflammatory effects. The phase 2 basket study design offers an efficient approach to advance TEV-45874to confirmatory phase 3 studies.