Phase 2 Study of pH Gastrilex™ (Enteric-Coated Amorphous Calcium Carbonate Capsules) in Moderate-to-Severe Crohn's Disease

This study aims to evaluate the safety, tolerability, and efficacy of pH Gastrilex™, an enteric-coated capsule formulation containing amorphous calcium carbonate (ACC), manufactured by Amorphical Ltd., Israel, in adults with moderate-to-severe Crohn's disease.

Crohn's disease is a chronic, relapsing inflammatory bowel disease associated with intestinal inflammation and impaired epithelial barrier function. The therapeutic rationale for pH Gastrilex™ is based on the hypothesis that local intestinal acidification may contribute to inflammation. The formulation is designed for intestinal release of ACC, whose carbonate component is proposed to buffer the local intestinal acidity through its acid-neutralizing capacity.

This is a single-center, Phase 2, randomized, double-blind, placebo-controlled, parallel-group study evaluates the safety, tolerability, and efficacy of PH Gastrilex™ in adults with moderate-to-severe Crohn's disease (CDAI≥220). Participants are randomized in a 1:1 ratio to receive PH Gastrilex™ or matching placebo for 12 weeks, in addition to best available treatment (BAT).

Following the initial 12-week double-blind phase, participants receiving placebo switch to pH Gastrilex™, while those initially assigned to active treatment continue with pH Gastrilex™ for an additional 12 weeks. Participants completing Week 24 are offered the option to continue treatment with pH Gastrilex™ for a further 48 weeks in an open-label extension, through Week 72.

Clinical assessments include disease activity measured by the Crohn's Disease Activity Index (CDAI), endoscopic evaluation by colonoscopy, and health-related quality of life assessed using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Inflammatory markers, including C-reactive protein (CRP) and fecal calprotectin, are also assessed during the study. Safety and tolerability are assessed through adverse event monitoring, clinical examinations, and laboratory evaluations.

PH Gastrilex™ (Amorphous Calcium Carbonate)

Drug: PH Gastrilex

Placebo Followed by PH Gastrilex™ (Amorphous Calcium Carbonate)

Drug: Placebo Comparator

Enteric-coated capsules containing amorphous calcium carbonate (ACC), administered as 2 capsules four times daily (200 mg elemental calcium per capsule; 1,600 mg/day).

Weeks 1-12: pH Gastrilex™ + BAT. Weeks 12-24: Continue pH Gastrilex™ + BAT. Weeks 24-72: Optional extension: continue pH Gastrilex™ + BAT.

Matching placebo capsules for the first 12 weeks, followed by PH Gastrilex™ at the same dosing regimen (2 capsules four times daily; 1,600 mg elemental calcium/day).

Weeks 1-12: Placebo + BAT. Weeks 12-24: Switch to pH Gastrilex™ + BAT. Weeks 24-72: Optional extension: continue pH Gastrilex™ + BAT.

Plazo: Baseline and 12 weeks

Change in CDAI score from baseline to Week 12. The Crohn's Disease Activity Index (CDAI) is a composite score assessing Crohn's disease activity based on clinical and patient-reported parameters

Plazo: Baseline and 24 weeks

Change in CDAI score from baseline to Week 24. The Crohn's Disease Activity Index (CDAI) is a composite score assessing Crohn's disease activity based on clinical and patient-reported parameters

Plazo: Baseline, Week 12, Week 24, and Week 72

The percentage of participants achieving clinical remission, defined as Crohn's Disease Activity Index (CDAI) ≤150.

Plazo: Baseline, Week 12, Week 24, and Week 72

The percentage of participants with a reduction in CDAI of at least 100 points from baseline.

Plazo: Baseline, Week 12, Week 24, and Week 72

Change from baseline in the mean daily number of liquid or very soft stools, as assessed by the CDAI over a 7-day period

Plazo: Baseline, Week 12, Week 24, and Week 72

Change in the CDAI abdominal pain component, assessed daily on a 4-point scale (0 = none; 1 = mild; 2 = moderate; 3 = severe).

Plazo: Baseline, Week 24, and Week 72

Achieving a ≥50% reduction from baseline in the Simple Endoscopic Score for Crohn's Disease (SES-CD).

Plazo: Baseline, Week 12, Week 24, and Week 72

Change in Short Inflammatory Bowel Disease Questionnaire (SIBDQ) score (range 10-70; higher scores indicate better quality of life).

Plazo: Week 24 through Week 72

Percentage of participants maintaining clinical remission (CDAI≤150) during the open-label extension.

Plazo: Week 24 through Week 72

Percentage of participants maintaining clinical response, defined as a reduction in CDAI score of at least 100 points from baseline, during the open-label extension.

Plazo: Baseline, Week 12, Week 24, and Week 72

Percentage of participants achieving CRP levels ≤0.5 mg/dL.

Plazo: Baseline, Week 12, Week 24, and Week 72

Percentage of participants achieving fecal calprotectin levels ≤250 µg/g.

Prospective, Randomized, Parallel, Double Blind, Placebo-Controlled Study, Followed by an Open Label Extension, to Assess the Safety, Tolerability, and Efficacy of pH Gastrilex™ (Enteric-Coated Capsules Containing Amorphous Calcium Carbonate) Administered Concomitantly With Best Available Treatment (BAT) in the Treatment of Adult Subjects With Moderate to Severe Crohn's Disease