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Abstract: SA-PO307

SYNB8802 Lowers Urinary Oxalate During a Diet-Controlled Study in Patients with Roux-en-Y Gastric Bypass

Session Information

Category: Bone and Mineral Metabolism

  • 502 Bone and Mineral Metabolism: Clinical

Authors

  • Kurtz, Caroline B., Synlogic, Cambridge, Massachusetts, United States
  • Wheeler, Alistair, Synlogic, Cambridge, Massachusetts, United States
  • Blasbalg, Julie Beth, Synlogic, Cambridge, Massachusetts, United States
  • Denney, William, Human Predictions, LLC, Cambridge, Massachusetts, United States
  • Macdougall, James, Synlogic, Cambridge, Massachusetts, United States
  • Wood, Kyle, University of Alabama, Birmingham, Alabama, United States
  • Brennan, Aoife M., Synlogic, Cambridge, Massachusetts, United States
Background

Patients with Roux-en-Y (RnY) gastric bypass surgery are at risk for development of intestinal malabsorption which can increase the absorption of dietary oxalate, resulting in enteric hyperoxaluria (EH). Hyperoxaluria may lead to kidney stone formation, kidney damage, and deposition of oxalate in other tissues and organs. SYNB8802 is an engineered probiotic bacteria designed to consume oxalate in the GI tract and reduce urinary oxalate (UOx) absorption.

Methods

Study SYNB8802-CP-002 was a Phase 1b, randomized, placebo-controlled, single-center inpatient study in subjects with a history of RnY gastric bypass surgery. Subjects were placed on a 12-day diet-controlled study containing 300 mg of oxalate and 400 mg of calcium. A diet and placebo run-in period of 3 days was followed by oral administration of increasing dose levels of SYNB8802 up to 3x1011 lives cells or placebo for 12 days. 24-hour urine was collected daily from days -3 to 12 and analyzed for urine oxalate content as well as other analytes.

Results

SYNB8802-CP-002 enrolled 11 subjects (median (SD) age 56 (8.6), 1 M/10 F) with a history of RnY gastric bypass, and no prior kidney stones. Seven subjects received SYNB8802 and 4 patients received placebo. Two placebo subjects were excluded from the efficacy analysis because of major protocol violations (antibiotic use and incomplete dosing). The oxalate diet resulted in a baseline mean (SD) UOx of 29.4 (2.3) mg/24h for the placebo and 32.5 (9.0) mg/24h for the SYNB8802. SYNB8802 lowered UOx by -41.0% (p<0.01) compared to -8.8% (p=0.73) for placebo but the change over placebo (-35.3%) did not achieve statistical significance (p=0.16). A post-hoc pharmacometrics model incorporating the effects of dose and frequency showed a significant UOx lowering of -37.3% [95% CI: 45.9, 28.3] relative to placebo (p<0.05). The most common adverse events were mild to moderate and GI related. There were no SAEs.

Conclusion

SYNB8802 was well tolerated in patients with RnY gastric bypass and demonstrated the capacity to lower UOx. SYNB8802 should be further evaluated in subjects afflicted with kidney stone disease and EH.

Funding

  • Commercial Support – Synlogic Therapeutics, Inc.