Safety and Tolerability of SYNB8802 in Healthy Adult Volunteers and Adult Subjects With Enteric Hyperoxaluria

NCT04629170 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: SYNB8802-CP-001
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 4

Brief Summary

This Phase 1a/b, first-in-human, multiple dose-escalation, randomized, double-blinded, placebo-controlled study is evaluating SYNB8802 in healthy volunteers (HV) and subjects diagnosed with enteric hyperoxaluria (EH). Eligible subjects receive investigational product (IP) and undergo safety monitoring, evaluations, and subsequent follow-up after IP administration. In Part 2, all evaluations and assessments throughout this study may be conducted either at the clinical site or by a home healthcare professional at an alternative location (e.g., EH patient's home, hotel).

Conditions

Healthy; Enteric Hyperoxaluria

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Treatment-Emergent Adverse Events

  Toxicity is graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Adverse events (AEs) are reported based on clinical laboratory tests, vital signs, physical examinations, electrocardiograms, and any other medically indicated assessments from the time informed consent is signed through the end of the safety follow-up period. AEs are considered to be treatment emergent (TEAE) if they occur or worsen in severity after the first dose of study treatment. TEAEs are considered treatment-related if relationship to study drug is possibly related, probably related, or definitely related.

  33 Days

Study Arms (8)

MAD HV: SYNB8802 (1 x 10^11 live cells)

EXPERIMENTAL

HV subjects receive SYNB8802 (1 x 10\^11 live cells) TID for 5 days in the MAD study (Part 1).

Drug: SYNB8802

MAD HV: SYNB8802 (3 x 10^11 live cells)

EXPERIMENTAL

HV subjects receive SYNB8802 (3 x 10\^11 live cells) TID for 5 days in the MAD study (Part 1).

Drug: SYNB8802

MAD HV: SYNB8802 (1 x 10^12 live cells)

EXPERIMENTAL

HV subjects receive SYNB8802 (1 x 10\^12 live cells) TID for 5 days in the MAD study (Part 1).

Drug: SYNB8802

MAD HV: SYNB8802 (optional cohort 1)

EXPERIMENTAL

HV subjects receive SYNB8802 (at a dose to be determined based on the data from the first 3 cohorts) TID for 5 days in the MAD study (Part 1).

Drug: SYNB8802

MAD HV: SYNB8802 (optional cohort 2)

EXPERIMENTAL

HV subjects receive SYNB8802 (at a dose to be determined based on the data from the first 3 cohorts) TID for 5 days in the MAD study (Part 1).

Drug: SYNB8802

MAD HV: Placebo

PLACEBO COMPARATOR

HV subjects receive placebo TID for 5 days in the MAD study (Part 1).

Drug: Placebo

Crossover Arm 1: SYNB8802 crossover to Placebo

OTHER

In Part 2 subjects will be randomized (1:1) to receive SYNB8802 TID for 6 days and then, following a washout period, receive Placebo TID for 6 days.

Drug: SYNB8802; Drug: Placebo

Crossover Arm 2: Placebo crossover to SYNB8802

OTHER

In Part 2 subjects will be randomized (1:1) to receive Placebo TID for 6 days and then, following a washout period, receive SYNB8802 TID for 6 days.

Drug: SYNB8802; Drug: Placebo

Interventions

SYNB8802 DRUG

SYNB8802 is formulated as a nonsterile solution intended for oral administration

Crossover Arm 1: SYNB8802 crossover to Placebo; Crossover Arm 2: Placebo crossover to SYNB8802; MAD HV: SYNB8802 (1 x 10^11 live cells); MAD HV: SYNB8802 (1 x 10^12 live cells); MAD HV: SYNB8802 (3 x 10^11 live cells); MAD HV: SYNB8802 (optional cohort 1); MAD HV: SYNB8802 (optional cohort 2)

Placebo DRUG

In order to maintain study blinding, matching placebo in identical packaging will be manufactured using an inactive powder

Crossover Arm 1: SYNB8802 crossover to Placebo; Crossover Arm 2: Placebo crossover to SYNB8802; MAD HV: Placebo

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 to ≤ 64 years.
• Body mass index (BMI) 18.5 to 28 kg/m2.
• Able and willing to voluntarily complete the informed consent process.
• Available for and agree to all study procedures, including feces, urine, and blood collection and adherence to diet control, inpatient monitoring, follow-up visits, and compliance with all study procedures.
• Female subjects who meet 1 of the following:
• Premenopausal woman with at least 1 of the following:
• i. Documented hysterectomy ii. Documented bilateral salpingectomy iii. Documented bilateral oophorectomy iv. Documented tubal ligation/occlusion v. Sexual abstinence is preferred or usual lifestyle of the subject c. Postmenopausal women (12 months or more amenorrhea verified by follicle- stimulating hormone \[FSH\] assessment and over 45 years of age in the absence of other biological or physiological causes).

You may not qualify if:

• Acute or chronic medical (including COVID-19 infection), surgical, psychiatric, or social condition or laboratory abnormality that may increase subject risk associated with study participation, compromise adherence to study procedures and requirements, or may confound interpretation of study safety or PD results and, in the judgment of the investigator, would make the subject inappropriate for enrollment.
• Body mass index (BMI) \< 18.5 or \> 28 kg/m2.
• Oxalobacter formigenes carrier.
• Pregnant (self or partner), or lactating.
• Unable or unwilling to discontinue vitamin C supplementation for the study duration.
• History of or current immunodeficiency disorder including autoimmune disorders and human immunodeficiency virus (HIV) antibody positivity.
• Hepatitis B surface antigen positivity (subjects with hepatitis B surface antibody positivity and hepatitis B core antibody positivity are not excluded, provided that the hepatitis B surface antigen is negative).
• Hepatitis C antibody positivity, unless a hepatitis C virus ribonucleic acid test is performed, and the result is negative.
• History of febrile illness, confirmed bacteremia, or other active infection deemed clinically significant by the investigator within 30 days prior to the anticipated first dose of IMP.
• History of (within the past month) passage of 3 or more loose stools per day; where 'loose stool' is defined as a Type 6 or Type 7 on the Bristol Stool Chart (see Appendix 1: Bristol Stool Chart).
• History of kidney stones, renal or pancreatic disease.
• GI disorder (including inflammatory or irritable bowel disorder of any grade and surgical removal of bowel sections) that could be associated with increased UOx levels.
• Active or past history of GI bleeding within 60 days prior to the Screening Visit as confirmed by hospitalization-related event(s) or medical history of hematemesis or hematochezia.
• Intolerance of or allergic reaction to EcN, esomeprazole or PPIs in general, or any of the ingredients in SYNB8802 or placebo formulations.
• Any condition (e.g., celiac disease, gastrectomy, bypass surgery, ileostomy), prescription medication, or over-the-counter product that may possibly affect absorption of medications or nutrients.

Sponsors & Collaborators

• Synlogic: lead

Study Sites (4)

Urological Associates of Southern Arizona (open to remote participation)

Tucson, Arizona, 85715, United States

Location

Genesis Clinical Research

Tampa, Florida, 33603, United States

Location

Knoxville Kidney Center

Knoxville, Tennessee, 37923, United States

Location

PRA Health Sciences

Salt Lake City, Utah, 84124, United States

Location

Study Design

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

Model Details: Part 1 - randomized, placebo-controlled multiple-dose escalation Part 2 - randomized, placebo-controlled crossover

Study Record Dates

• First Submitted: November 9, 2020
• First Posted: November 16, 2020
• Study Start: November 4, 2020
• Primary Completion: January 17, 2023
• Study Completion: January 17, 2023
• Last Updated: March 8, 2024

Record last verified: 2024-03

Locations

US (4)