Safety, Tolerability, and Pharmacodynamics of SYNB8802v1 in Subjects With History of Gastric Bypass Surgery or Short-bowel Syndrome
Condition: Enteric Hyperoxaluria
MeSH terms: Short Bowel Syndrome
Study type: Interventional
Phase: Early Phase 1

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.
    

Detailed 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.
    

Intervention name(s): SYNB8802v1; Placebo
Intervention type(s): Drug; Other
Intervention description(s): SYNB8802v1 is an orally administered, non-systemically absorbed live biotherapeutic developed for the treatment of EH. The strain converts oxalate to formate and CO2, two naturally occurring GI metabolites.
SYNB8802 was developed by engineering a pathway for oxalate degradation in a probiotic strain of Escherichia coli Nissle 1917 (EcN). It is intended to act within the GI tract to reduce the oxalate levels in patients with EH by converting oxalate to formate and CO2, two naturally occurring GI metabolites.; placebo powder will be aliquoted into high density polyethylene (HDPE) bottles and diluted in the same formulation buffer as SYNB8802v1 lyophilized powder. The placebo consists of corn starch and dyes to color match the placebo to the SYNB8802v1 powder for oral suspension
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Placebo control (3:2 [active: placebo]) is included for a better understanding of the safety and tolerability of SYNB8802v1.
Masking: Double (Participant, Investigator)
Primary purpose: Treatment