Safety, Tolerability, and Pharmacodynamics of SYNB8802v1 in Subjects With History of Gastric Bypass Surgery or Short-bowel Syndrome

Enteric Hyperoxaluria Clinical Trial

Official title: A Double-Blind, Randomized, Placebo-controlled Study to Assess the Safety, Tolerability, and Pharmacodynamics of SYNB8802v1 in Subjects With History of Gastric Bypass Surgery or Short-bowel Syndrome

Status Completed

Clinical Trial Summary

Study SYNB8802-CP-002 is designed to assess safety, tolerability, and oxalate lowering, in subjects with a history of gastric bypass surgery or short-bowel syndrome. In addition, this study will explore other PD effects relative to baseline as well as predictors of efficacy and tolerability.

Clinical Trial Description

This is a double-blind (sponsor-open), randomized (3:2), placebo-controlled, inpatient study evaluating the safety and tolerability of SYNB8802v1 in subjects with a history of gastric bypass surgery or short-bowel syndrome. An interim analysis of results by an unblinded statistician will be performed after 10 subjects.

The study includes the following periods:

• Screening period (27 days)

• Diet run in (3 days)

• Dosing Period (12 days)

• Safety follow-up (28 days)

The maximum duration of the inpatient stay will be 17 days (Day -4 to Day 13). Subjects will report to the clinical research unit (CRU) on Day -4 and will complete a 3-day diet run-in period (Days -3 to -1) during which they will consume an AOLC diet (refer to Diet Manual for details). Dietary oxalate and calcium will be distributed across 3 meals per day, and subjects will maintain this diet until the end of the dosing period. A proton pump inhibitor (PPI, esomeprazole) will be administered once daily (QD), 60-90 minutes before breakfast, from the start of the diet run-in period (Day -3) until the end of the dosing period (Day 12).

On Day 1, subjects will be randomly assigned to treatment with SYNB8802v1 or placebo (collectively referred to as investigational medicinal product [IMP]). The dosing period consists of 12 days following a dose escalation plan from 1 × 1011 live cells QD to 3 × 1011 live cells TID; the dosing period for each dose level includes a 2-day dose ramp and a 3-day steady-state period. During the dose ramp, placebo will be administered such that all subjects receive IMP dosing TID. On the morning of the first day of the run-in period (Day -3), a forced void urine sample will be collected to completely empty the bladder before the first placebo dose administration. A 24-hour urine collection will then be started and will continue throughout the in-patient period. In addition, daily 24-hour fecal samples will be collected. Subjects will be released from the CRU upon the completion of safety assessments on Day 13 (the day after the last dose of IMP). Safety follow-up visits (calls) will occur every 7 (±2) days until 28 (±2) days after the last dose of IMP. ;

Related Conditions & MeSH terms

• Enteric Hyperoxaluria
• Short Bowel Syndrome

• NCT number: NCT05377112
• Study type: Interventional
• Source: Synlogic
• Status: Completed
• Phase: Early Phase 1
• Start date: March 29, 2022
• Completion date: December 7, 2022