Safety and Tolerability of SYNB1934 in Healthy Adult Volunteers

NCT04984525 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: SYNB1934-CP-001
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase 1, first-in-human, multiple dose-escalation, randomized, double-blinded, placebo-controlled study is evaluating SYNB1934 in healthy volunteers (HV). Eligible subjects receive investigational product (IP) and undergo safety monitoring, evaluations, and subsequent follow-up after IP administration.

Conditions

Healthy

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.

  70 days

Study Arms (6)

Part 1 Cohort 1 MAD HV: SYNB1934 (3 x 10^11 live cells)

EXPERIMENTAL

HV subjects receive SYNB1934 (3 x 10\^11 live cells) At least 3 times per day (TID) on Treatment Day 1 and once at breakfast on Treatment Day 2

Drug: SYNB1934

Part 1 Cohort 2 Crossover HV: SYNB1934 (6 x 10^11 live cells)

EXPERIMENTAL

HV subjects receive SYNB1934 (6 x 10\^11 live cells) At least 3 times per day (TID) on Treatment Day 1 and once at breakfast on Treatment Day 2 Following a ≥ 7-day washout period HV subjects receive SYNB1618 (6 x 10\^11 live cells), at least 3 times per day (TID) on Treatment Day 1 and once at breakfast on Treatment Day 2

Drug: SYNB1934; Drug: SYNB1618

Part 1 Cohort 3 MAD HV: SYNB1934 (1 x 10^12 live cells)

EXPERIMENTAL

HV subjects receive SYNB1934 (1 x 10\^12 live cells) At least 3 times per day (TID) on Treatment Day 1 and once at breakfast on Treatment Day 2

Drug: SYNB1934

Part 1 Cohort 4 MAD HV: SYNB1934 (optional)

EXPERIMENTAL

HV subjects receive SYNB1934 (at a dose to be determined based on the data from the first 3 cohorts) At least 3 times per day (TID) on Treatment Day 1 and once at breakfast on Treatment Day 2

Drug: SYNB1934

Part 1 Cohort 5 MAD HV: SYNB1934 (optional)

EXPERIMENTAL

HV subjects receive SYNB1934 (at a dose to be determined based on the data from the first 3 cohorts) At least 3 times per day (TID) on Treatment Day 1 and once at breakfast on Treatment Day 2

Drug: SYNB1934

Part 2 Crossover with PPI vs No PII

EXPERIMENTAL

HV subjects receive SYNB1934 (at or below the MTD from Part 1) with PPI At least 3 times per day (TID) on Treatment Day 1 and once at breakfast on Treatment Day 2 Following a ≥ 14-day washout period HV subjects receive SYNB1934 (at or below the MTD from Part 1) without PPI At least 3 times per day (TID) on Treatment Day 1 and once at breakfast on Treatment Day 2

Drug: SYNB1934

Interventions

SYNB1934 DRUG

SYNB1934 is formulated as a nonsterile solution intended for oral administration

Part 1 Cohort 1 MAD HV: SYNB1934 (3 x 10^11 live cells); Part 1 Cohort 2 Crossover HV: SYNB1934 (6 x 10^11 live cells); Part 1 Cohort 3 MAD HV: SYNB1934 (1 x 10^12 live cells); Part 1 Cohort 4 MAD HV: SYNB1934 (optional); Part 1 Cohort 5 MAD HV: SYNB1934 (optional); Part 2 Crossover with PPI vs No PII

SYNB1618 DRUG

SYNB1618 is formulated as a nonsterile solution intended for oral administration

Part 1 Cohort 2 Crossover HV: SYNB1934 (6 x 10^11 live cells)

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age ≥ 18 to ≤ 64 years.
• 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 women 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 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 \< 18.5 or ≥ 35 kg/m2.
• History of or current immunodeficiency disorder including 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.
• Inflammatory or irritable bowel disorder of any grade experienced within the previous 60 days.
• Active or past history of gastrointestinal 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 any of the ingredients in SYNB1934 or placebo formulations. (For subjects who may be randomized to receive SYNB1618, intolerance of or allergic reaction to any of the ingredients in the SYNB1618 formulation.)
• 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.
• Currently taking or plans to take any type of systemic (e.g., oral or intravenous) antibiotic within 30 days prior to Day -1 through the final day of inpatient monitoring. Exception: topical antibiotics are allowed.
• Major surgery (an operation upon an organ within the cranium, chest, abdomen, or pelvic cavity) or inpatient hospital stay within the past 3 months prior to Screening.
• Planned surgery, hospitalizations, dental work, or interventional studies between Screening and last anticipated visit.
• Taking or planning to take probiotic supplements (enriched foods excluded) within 30 days prior to Day -1 through the Safety Follow-up Period.

Sponsors & Collaborators

• Synlogic: lead

Study Sites (1)

High Point Clinical Trials Center

High Point, North Carolina, 27265, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Part 1: Triple (Participant, Care Provider, Investigator) Double-blind (Sponsor-open) Part 2: Open-label
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2021
• First Posted: July 30, 2021
• Study Start: July 2, 2021
• Primary Completion: December 10, 2021
• Study Completion: December 10, 2021
• Last Updated: May 18, 2022

Record last verified: 2022-05

Locations

US (1)