Lead Investigator Perspectives on GALAXI-2 and GALAXI-3 Study Designs

EP: 1.Overview of Crohn’s Disease and Current Gaps in Access

EP: 2.Treatment Landscape of Crohn’s Disease and Mechanisms of Action

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EP: 3.Lead Investigator Perspectives on GALAXI-2 and GALAXI-3 Study Designs

GALAXI-2 and GALAXI-3 Study Design Perspectives

Innovative Trial Design and Methodology

The GALAXI-2 and GALAXI-3 studies represent a landmark advancement in Crohn’s disease clinical trial methodology, recently published in The Lancet. These twin trials employed a uniquely rigorous triple-dummy, active comparator design that randomly assigned patients to guselkumab, ustekinumab (active comparator) or placebo with complete blinding. This design enabled head-to-head comparison with an established therapy while maintaining placebo control according to regulatory guidelines. The studies utilized a treat-through model where responding patients continued their assigned therapy seamlessly from induction into maintenance without rerandomization, providing more robust data interpretation for long-term efficacy and safety assessment. This approach more closely mirrors clinical practice patterns than traditional trial designs.

Patient Population and End Point Rigor

The trials demonstrated exceptional inclusivity by incorporating biologic-naive and biologic-experienced patients, significantly enhancing generalizability to real-world clinical practice. Endoscopic assessments were systematically performed at baseline, week 12 and week 48, aligning with STRIDE-II treatment targets for comprehensive disease evaluation. A particularly innovative aspect was the use of composite primary end points measured at the individual patient level rather than the population level. Success required patients to achieve both clinical response/remission and endoscopic response at both week 12 and week 48, representing a departure from traditional end point measurement and adding substantial rigor to outcome assessment.

Statistical Power and Clinical Relevance

The identical design of GALAXI-2 and GALAXI-3 as separate but coordinated trials provided additional confidence in results through replication while enabling pooled analysis for enhanced statistical power. This design was crucial for detecting potentially smaller adjusted deltas between guselkumab and ustekinumab in a head-to-head comparison. The active comparator design against ustekinumab, a cornerstone therapy in moderate to severe Crohn’s disease, represents a significant departure from traditional placebo-controlled studies and provides clinically meaningful comparative efficacy data. The comprehensive trial architecture establishes a new paradigm for future moderate to severe Crohn’s disease studies, combining methodological rigor with clinical practice relevance.