STARS Phase 3 Trial: Once-Weekly Apraglutide Reduces Parenteral Support in Short Bowel Syndrome-Intestinal Failure.

BACKGROUND & AIMS: Patients with short bowel syndrome and intestinal failure (SBS-IF) depend on parenteral support (PS) to meet nutritional/fluid requirements. Apraglutide, a once-weekly, long-acting glucagon-like peptide-2 analog, promotes intestinal adaptation and may reduce PS dependence. The phase 3 STARS trial evaluated the efficacy and safety of apraglutide versus placebo in SBS-IF. METHODS: In this global, phase 3, double-blind, placebo-controlled trial, eligible patients were randomized 2:1 to once-weekly subcutaneous apraglutide or placebo, stratified by remnant intestinal anatomy (stoma or colon-in-continuity [CIC]). The primary endpoint was relative change from baseline in weekly PS volume at week 24 in the overall population. Key secondary endpoints included relative PS volume change in the stoma subgroup, days off PS (overall and CIC), and enteral autonomy (CIC). A safety analysis was conducted. RESULTS: Overall, 163 patients (80 stoma, 83 CIC) were randomized and dosed. Apraglutide significantly reduced weekly PS volume from baseline versus placebo at week 24 in the overall population (mean relative change, -25.5% vs -12.5%; P =.001) and stoma subgroup (-25.6% vs -7.8%; P <.001). A higher proportion of patients receiving apraglutide versus placebo achieved reduction of ≥1 day/week of PS at week 24 (43.0% vs 27.5%; P =.040). At week 48 (CIC), in the apraglutide versus placebo arms, the proportions of patients achieving reduction of ≥1 day/week of PS and enteral autonomy were 51.8% versus 44.4% (P =.348) and 12.5% versus 7.4% (nominal P =.387), respectively. Apraglutide was well tolerated with a favorable safety profile. CONCLUSION: Once-weekly subcutaneous apraglutide significantly reduced PS requirements in patients with SBS-IF with a well-tolerated safety profile.