AIM-IBD: A Microbiome-Targeted Supplement in Mild-to-Moderate Ulcerative Colitis

Proportion of Participants Achieving Composite Clinical-Plus-Biochemical Remission at Week 24

Responder defined by all four criteria at Week 24: (1) rectal bleeding subscore = 0 on the Mayo 0-3 scale (lower = less bleeding; 0 = no blood seen); (2) stool frequency subscore ≤1 on the Mayo 0-3 scale (lower = fewer stools above the participant's normal) with at least a 1-point decrease from baseline; (3) fecal calprotectin ≤250 µg/g (lower = less mucosal inflammation), measured centrally; (4) no rescue therapy, prohibited escalation, UC-related hospitalization, colectomy, or discontinuation for lack of efficacy through Week 24. Participants not meeting any criterion, or with missing Week 24 data, are counted as non-responders (non-responder imputation). Higher proportion = greater treatment benefit. Analyzed in the intention-to-treat population using stratified Cochran-Mantel-Haenszel adjusted for randomization stratification factors, reporting absolute risk difference with Newcombe 95% CI.

Proportion of Participants With Endoscopic Improvement at Week 24

Responder defined as Mayo endoscopic subscore ≤1 at Week 24 (scale 0-3; lower = less inflammation; 0 = normal, 1 = mild erythema/decreased vascular pattern, 2 = marked erythema/friability/erosions, 3 = spontaneous bleeding/ulceration). Week 24 assessment is by protocol-mandated flexible sigmoidoscopy of the most inflamed segment with standardized image/video capture, scored by two independent blinded readers; discordant scores or scores crossing the ≤1 vs \>1 threshold are adjudicated by a third blinded reader (adjudicator score = trial-of-record). Participants meeting any treatment-failure criterion before Week 24, or not undergoing the Week 24 endoscopy without documented medical exception, are counted as non-responders. A completer-only sensitivity analysis is prespecified. Higher proportion = greater treatment benefit. Analyzed in the intention-to-treat population using stratified Cochran-Mantel-Haenszel; effect estimate is absolute risk difference (Newcombe 95% CI).

Proportion of Participants With Deep Biochemical Remission at Week 24

Responder defined as fecal calprotectin ≤150 µg/g at Week 24, measured centrally using a validated assay. Fecal calprotectin is a stool neutrophil-derived biomarker of intestinal inflammation: healthy adults typically \<50 µg/g; well-controlled UC \<150-250 µg/g; active disease often several hundred to several thousand µg/g. The 150 µg/g threshold is stricter than the 250 µg/g threshold used in the primary composite endpoint and corresponds to the deep biochemical remission target in STRIDE-II treat-to-target guidance. Participants meeting any treatment-failure criterion before Week 24, or with missing Week 24 calprotectin, are counted as non-responders (non-responder imputation). A completer-only sensitivity analysis is prespecified. Higher proportion = greater treatment benefit. Analyzed in the intention-to-treat population using stratified Cochran-Mantel-Haenszel adjusted for randomization stratification factors; effect estimate is absolute risk difference (Newcombe 95% CI).

Change in Fecal Calprotectin From Baseline to Week 24

Continuous endpoint quantifying treatment effect on intestinal inflammation. Fecal calprotectin is a stool neutrophil-derived biomarker measured centrally using a validated assay at baseline and Week 24; healthy adults typically \<50 µg/g, well-controlled UC \<150-250 µg/g, active disease often several hundred to several thousand µg/g, with no fixed upper limit. Lower values indicate less mucosal inflammation. Values are log-transformed (natural log, after substituting half the lower limit of quantification for any below-LLOQ result), and the treatment effect is summarized as the geometric mean ratio of active vs placebo at Week 24 with 95% confidence interval, derived from a mixed model for repeated measures with treatment, visit, treatment-by-visit interaction, log baseline calprotectin, and randomization stratification factors as fixed effects. A geometric mean ratio below 1 indicates a greater reduction in fecal calprotectin in the active arm relative to placebo.

Change in Fecal Calprotectin From Baseline to Week 12

Continuous endpoint quantifying early treatment effect on intestinal inflammation, prespecified as an interim biomarker readout midway through the 24-week treatment period. Fecal calprotectin is a stool neutrophil-derived biomarker measured centrally using a validated assay at baseline and Week 12; healthy adults typically \<50 µg/g, well-controlled UC \<150-250 µg/g, active disease often several hundred to several thousand µg/g. Lower values indicate less mucosal inflammation. Values are log-transformed (natural log, after substituting half the lower limit of quantification for any below-LLOQ result) and the treatment effect is summarized as the geometric mean ratio of active vs placebo at Week 12 with 95% confidence interval, derived from a mixed model for repeated measures with treatment, visit, treatment-by-visit interaction, log baseline calprotectin, and randomization stratification factors as fixed effects. A ratio below 1 indicates greater reduction in the active arm vs placebo.