Safety and Tolerability of SYNB1020-CP-001

Study Overview
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Brief Summary
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A Phase 1, First-in-human, Oral Single and Multiple Dose-Escalation, Randomized, Double-blinded, Placebo-controlled Study of SYNB1020 in Healthy Adult Volunteers to Evaluate Safety, Tolerability, Dosing, and Pharmacodynamics

Detailed Description
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This Phase 1, dose-escalating, randomized, double-blinded study will evaluate SYNB1020 in placebo-controlled cohorts within the following 2 study parts: Part 1: A single-ascending dose (SAD) study conducted in an inpatient setting over 6 days in healthy volunteer male and female subjects evaluated in up to 7 dose cohorts to identify the maximum tolerated dose (MTD) within the single dose range studied; and Part 2: A multiple-ascending dose (MAD) study conducted in an inpatient setting over 22 days in healthy volunteer male and female subjects evaluated in up to 4 dose cohorts that were proven tolerable in the SAD part of the study to identify the MTD of SYNB1020 within the multiple-dose range studied. Up to 48 subjects may be enrolled in this part of the study. Subjects will be screened for eligibility within 30 days prior to enrollment, with evaluations of exercise habits, gastrointestinal (GI) signs and symptoms, fecal patterns (frequency, consistency), recent or current antibiotic exposure, and laboratory measurements. Eligible patients will be admitted to an inpatient facility for investigational product (IP) administration, safety monitoring, and collection of blood, urine, and fecal samples for pharmacokinetic and pharmacodynamic evaluations.

Official Title
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A Phase 1, First-in-human, Oral Single and Multiple Dose-Escalation, Randomized, Double-blinded, Placebo-controlled Study of SYNB1020 in Healthy Adult Volunteers to Evaluate Safety, Tolerability, Dosing, and Pharmacodynamics

Conditions
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Healthy Volunteer, Urea Cycle Disorder

Intervention / Treatment
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* Drug: Placebo
* Drug: SYNB1020


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Age 18 to 64 years Healthy volunteer Males and Females; Females must be of non childbearing potential Able and willing to complete informed consent process Available for and agree to all study procedures Screening Labs within normal range Key Exclusion Criteria: Acute or chronic medical, surgical, psychiatric, social or laboratory abnormality Body mass index < 18.5 or ≥ 30 kg/m2 Intolerance of or allergic reaction to E. coli Nissle or any of the ingredients in SYNB1020 or placebo formulations; allergies to common foods (e.g., eggs, milk, soy, nuts). Prior participation in a study with SYNB1020 Evidence or history of clinical signification hematological, renal, endocrine, pulmonary, GI cardiovascular, hepatic, psychiatric, neurologic or allergic disease Personal or family history of UCD

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, Double-blinded, Placebo controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SYNB1020<br>SYNB1020 | Drug: SYNB1020<br>* Investigational Product<br>|
| Placebo Comparator: Placebo<br>100 mL masking solution | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events, Laboratory Assessments and ECGs to measure Safety and Tolerability of SYNB1020 | Will be measured by assessing nature and frequency of AEs, Laboratory Assessments, and ECGs | 3 months from study entry | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GI tolerability measured using the Gastrointestinal Symptom Rating Scale (GSRS) | Will be measured using the Gastrointestinal Symptom Rating Scale (GSRS) | 1 month of study entry | 
| SYNB1020 kinetics measured by qPCR fecal assays | Will be measured by qPCR fecal assays | 3 months from study entry |