P0773Amorphous Calcium Carbonate (ACC) in moderate-to-severe Crohn’s disease: 24-Week and long-term results from a randomized, placebo-controlled trial with open-label extension

Background Amorphous Calcium Carbonate (ACC; Amorphical, Israel) nanoparticles1,2 was administered orally in enteric-coated capsules, designed to locally neutralize the acidic inflammatory microenvironment in inflammatory bowel disease (IBD), including Crohn’s disease (CD)3,4, while providing supplemental calcium (Fig 1). Methods This Phase 2, randomized, double-blind, placebo-controlled trial enrolled adults with moderate-to-severe CD (CDAI ≥220). Patients were randomized 1:1 to receive ACC (1,600 mg elemental Ca/day) or placebo for 12 weeks with standard care, followed by a 12-week open-label (OL) phase in which all participants received ACC. Those completing 24 weeks were offered a 1-year OL extension with continued treatment (Fig 2). Efficacy was assessed across standard CD parameters, with current analyses focusing on CDAI, stool frequency, and abdominal pain scores. Results Of 23 enrolled patients, 20 completed Week 12 onward and were included in the efficacy analysis. About 80% received concomitant CD treatment. Baseline CDAI scores were 290 ± 17 in the ACC arm and 309 ± 20 in the placebo arm (n = 10 each). At Week 12, mean CDAI decreased by -102 ± 33 (n = 8) and -47 ± 33 points (n = 10), respectively. Stool frequency declined from 5.4 ± 0.97 to 4.8 ± 1.49 per day in the ACC group and from 6.2 ± 0.72 to 5.3 ± 0.94 in the placebo group. Abdominal-pain scores improved from 2.1 ± 0.21 to 1.1 ± 0.39 and from 2.2 ± 0.13 to 1.6 ± 0.29, respectively. At Week 24, following OL treatment, early-start patients (ACC → ACC, n = 7) achieved a mean CDAI of 110 ± 30, compared with 194 ± 38 among delayed starters (Placebo → ACC, n = 8). Mean stool frequency decreased to 3.6 ± 1.16 vs 3.7 ± 1.09 per day, with greater improvement in abdominal-pain scores among early starters (0.7 ± 0.3 vs 1.4 ± 0.4). Among 8 patients who followed for ≥Week 48, five (63%) maintained clinical remission (CDAI <150); one showed sustained improvement (-154 points), one remained stable, and one exhibited fluctuating disease activity with intermittent remission. ACC was well tolerated, with no treatment-related AEs or safety signals. Conclusion ACC demonstrated numerically consistent and clinically meaningful improvements in CDAI (mean CDAI <150 in the early-start arm; >100-point improvement in the delayed-start arm), stool frequency, and abdominal pain, with a favorable safety profile. Continuous exposure from baseline was associated with more sustained clinical responses compared with delayed start. The dual mechanism of ACC, localized acid neutralization and calcium delivery, represents a novel therapeutic approach in CD. Additional data from the long-term follow-up and controlled studies will further establish the efficacy of ACC in CD. References: 1. Meiron OE, Bar-David E, Aflalo ED, Shechter A, Stepensky D, Berman A, Sagi A. Solubility and bioavailability of stabilized amorphous calcium carbonate. J Bone Miner Res. 2011;26(2):364-72. 2. Natan Y, Blum YD, Arav A, Poliansky Y, Neuman S, Ecker Cohen O, Ben Y. Amorphous Calcium Carbonate Shows Anti-Cancer Properties That are Attributed to Its Buffering Capacity. Cancers (Basel). 2023;15(15):3785. 3. Cartwright IM, Dowdell AS, Lanis JM, Brink KR, Mu A, Kostelecky RE, Schaefer REM, Welch N, Onyiah JC, Hall CHT, Gerich ME, Tabor JJ, Colgan SP. Mucosal acidosis elicits a unique molecular signature in epithelia and intestinal tissue mediated by GPR31-induced CREB phosphorylation. Proc Natl Acad Sci U S A. 2021 May 18;118(20). 4. Cartwright IM, Curtis VF, Lanis JM, Alexeev EE, Welch N, Goldberg MS, Schaefer REM, Gao RY, Chun C, Fennimore B, Onyiah JC, Gerich ME, Dempsey PJ, Colgan SP. Adaptation to inflammatory acidity through neutrophil-derived adenosine regulation of SLC26A3. Mucosal Immunol. 2020 Mar;13(2):2 Conflict of interest: Dr. Segal, Arik: No conflict of interest Nevo- Shor, Anat: No conflict of interest Lipnizkiy, Inna: No conflict of interest Mohammad, Asla: No conflict of interest Irena, Kantor: No conflict of interest Bryan, Itkowitz: No conflict of interest Slutsky, Guy: Provision of writing assistance, medicines, equipment, or administrative support Ben, Yossi: Provision of writing assistance, medicines, equipment, or administrative support