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

NCT05377112 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: SYNB8802-CP-002
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Enteric Hyperoxaluria

Outcome Measures

Primary Outcomes (3)

• Safety and tolerability of SYNB8802v1, as assessed by measuring of vital signs

  Vital Signs Resting vital signs will be collected as specified in the protocol. Subjects are required to remain in the sitting position for at least 5 minutes prior to obtaining vital signs. A symptom-directed physical examination will be performed by trained medical personnel as specified in the protocol.

  17 days

• Safety and tolerability of SYNB8802v1 by assessing clinical laboratory tests

  The clinical laboratory tests listed in the protocol will be performed at the time points specified in the protocol's schedule of assessments.

  17 days

• Safety and tolerability of SYNB8802v1, as assessed by AEs, clinical laboratory tests, and vital sign measurements

  Adverse events will be assessed continuously by direct observation and subject event recording and interviews. The severity of AEs will be evaluated using the NCI CTCAE, version 5.0 criteria.

  43 days

Secondary Outcomes (1)

• Change from baseline in 24-hour excreted UOx among SYNB8802v1-treated subjects versus those treated with placebo.

  17 days

Study Arms (2)

SYNB8802v1

EXPERIMENTAL

Dose ramp to 1 × 1011 QD and then dose ramp to 3 × 1011 TID SYNB8802v1 live cells

Drug: SYNB8802v1

Placebo

PLACEBO COMPARATOR

Placebo will be administered during the dose ramp such that all subjects receive IMP dosing TID

Other: Placebo

Interventions

SYNB8802v1 DRUG

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.

SYNB8802v1

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 to ≤ 74 years.
• Able and willing to voluntarily complete the informed consent process.
• Available for, and agree to, all study procedures, including fixed diet, feces, urine, and blood
• collection, follow-up visits, and compliance with all study procedures.
• History of gastric bypass surgery (at least 12 months prior to Day 1) or short-bowel
• syndrome.
• If taking probiotic supplements (enriched foods excluded), has been on a stable, well tolerated dose for at least 2 weeks prior to Day 1.
• Women of childbearing potential must have a negative pregnancy test (human chorionic
• gonadotropin) at screening and at baseline prior to the start of IMP.
• Screening laboratory evaluations (e.g., chemistry panel, complete blood count with
• differential, prothrombin time, urinalysis) and electrocardiogram (ECG) must be within
• normal limits or judged not to be clinically significant by the investigator. Subjects with
• known diabetes should be well controlled and have an A1c of ≤ 8% within 3 months prior to Day 1.
• Agree to abstain from tobacco/nicotine use for the duration of the inpatient stay.
• Subjects who are HIV positive, on therapy with normal CD4 counts and undetectable viral loads, can be included.

You may not qualify if:

• Acute or chronic medical (including COVID-19 infection), surgical, psychiatric, or social condition or laboratory abnormality (except those that can be explained by malabsorption) that may increase subject risk associated with study participation, compromise adherence to study procedures and requirements, or may confound interpretation of results and, in the judgment of the investigator, would make the subject inappropriate for enrollment.
• Estimated glomerular filtration rate \< 45 mL/min/1.73 m2.
• History of kidney stones.
• Subjects taking supplements that contain vitamin C should continue to use their supplements at a constant dose throughout the study, having maintained a constant dose for 2 weeks prior to screening.
• Known primary hyperoxaluria.
• Pregnant or lactating.
• Administration or ingestion of any type of systemic (e.g., oral or intravenous) antibiotic within 5 half-lives of the agent prior to Day 1. Exception: topical antibiotics are allowed.
• Any co-morbid condition that may necessitate antibiotic use or disrupt the controlled diet during the study period.
• Intolerance of, or allergic reaction to, EcN, all PPIs, or any of the ingredients in SYNB8802v1 or placebo formulations.
• Dependence on alcohol or drugs of abuse.
• Administration or ingestion of an investigational drug within 30 days or 5 half-lives, whichever is longer, prior to screening visit, or current enrollment in an investigational study.
• History of inflammatory bowel disease.

Sponsors & Collaborators

• Synlogic: lead

Study Sites (1)

PPD, part of Thermo Fisher Scientific

Austin, Texas, 78744, United States

Location

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: double-blind (sponsor-open),
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Placebo control (3:2 \[active: placebo\]) is included for a better understanding of the safety and tolerability of SYNB8802v1.

Study Record Dates

• First Submitted: April 15, 2022
• First Posted: May 17, 2022
• Study Start: March 29, 2022
• Primary Completion: December 7, 2022
• Study Completion: December 7, 2022
• Last Updated: March 17, 2023

Record last verified: 2023-03

Locations

US (1)