Safety, Tolerability and Pharmacodynamics of SYNB1020

NCT03447730 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: SYNB1020-CP-002
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 5

Brief Summary

This Phase 1b/2a, randomized, double-blind, placebo-controlled study was designed to evaluate the safety, tolerability, and pharmacodynamics of SYNB1020 in hepatic insufficiency and cirrhosis patients with hyperammonemia, with dosing of the investigational medicinal product (IMP) administered in an inpatient unit and subsequent outpatient follow-up for SYNB1020 clearance in two study parts.

Conditions

Cirrhosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-Emergent Adverse Events

  Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03, as follows: Grade 1 (mild/asymptomatic; no intervention); Grade 2 (moderate; minimal intervention); Grade 3 (severe/medically significant; hospitalization indicated; disabling); Grade 4 (life-threatening; urgent intervention required). Adverse events (AEs) were reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, and any other medically indicated assessments, including subject interviews, from the time informed consent was signed through the end of the safety follow-up period. AEs were considered to be treatment emergent adverse events (TEAEs) if they occurred or worsened in severity after the first dose of study treatment. TEAEs were considered treatment-related if relationship to study drug was possibly related, probably related, definitely related, or a missing relationship.

  Up to 70 days

Secondary Outcomes (2)

• Number of Participants With Clearance of SYNB1020 From Feces

  Up to 65 days

• Daily Fasting Spot Venous Ammonia

  Up to 9 days

Study Arms (3)

Part 1: SYNB1020

EXPERIMENTAL

Part 1 comprised a sentinel open-label cohort of subjects enrolled sequentially to receive SYNB1020, which was administered orally at a dose of 5 × 10\^11 colony-forming units (CFU) 3 times daily (TID) given immediately after meals from Days 1 through 6.

Drug: SYNB1020

Part 2: SYNB1020

EXPERIMENTAL

Subjects randomized to receive SYNB1020 in Part 2 received SYNB1020 administered orally at a dose of 5 × 10\^11 CFU TID given immediately after meals from Days 1 through 6.

Drug: SYNB1020

Part 2: Placebo

PLACEBO COMPARATOR

Subjects randomized to receive control in Part 2 received matching placebo (100 mL masking solution) administered orally TID given immediately after meals from Days 1 through 6.

Other: Placebo

Interventions

SYNB1020 DRUG

SYNB1020 was supplied at a concentration of approximately 1 × 10\^11 CFU/mL in a buffered solution in 5 mL cryovials with a nominal 5 mL fill volume, administered with 100 mL of masking buffer solution.

Part 1: SYNB1020; Part 2: SYNB1020

Placebo OTHER

Subjects received placebo orally in a chilled buffered solution (100 mL).

Part 2: 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 \< 75 years
• Females must have been of non-childbearing potential
• Able and willing to complete informed consent process
• Available for and agreed to all study procedures
• Screening laboratory evaluations within defined acceptable limits or judged to be not clinically significant by the Investigator
• Diagnosis of chronic, stable, hepatic insufficiency with features of cirrhosis due to any etiology
• Evidence of elevated portal hypertension by either liver stiffness measurement, the presence of abdominal or esophageal varices, splenomegaly or ascites (Part 2 only)
• Elevated venous ammonia (Part 2 only)

You may not qualify if:

• Body mass index \< 18.5 or ≥ 40 kg/m\^2
• Administration or ingestion of an investigational drug within 8 weeks or 5 half-lives, whichever was longer, prior to screening or current enrollment in an investigational study
• Allergy to ranitidine or intolerance to any of the excipients (glycerol, CS Health Easy Fiber)
• Any condition, prescription medication or over-the-counter product that may possibly have affected absorption of medications or nutrients
• Dependence on drugs of abuse
• Apart from chronic liver disease, any acute or chronic medical, surgical, psychiatric, or social condition including history of cerebrovascular disease (stroke, transient ischemic attack) or dementia, or laboratory abnormality that may have increased the subject risk associated with study participation, compromised adherence to study procedures and requirements, confounded interpretation of the safety, kinetics, or PD results, and, in the judgment of the Investigator, made the subject inappropriate for enrollment
• Current or past hepatic encephalopathy of Grade 2 or higher requiring hospitalization
• Child-Turcotte-Pugh score \> 9
• History of liver transplant

Sponsors & Collaborators

• Synlogic: lead

Study Sites (5)

Southern California Research Center

Coronado, California, 92118, United States

Location

Inland Empire Liver Foundation

Rialto, California, 92377, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Texas Liver Institute

San Antonio, Texas, 78006, United States

Location

McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

MeSH Terms

Conditions

Fibrosis

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Interim futility analyses identified a lack of SYNB1020 efficacy (plasma ammonia AUC) compared with placebo, resulting in study termination.

Results Point of Contact

• Title: Andrew Marsh, Head Clinical Operations
• Organization: Synlogic

andrew.marsh@synlogictx.com

617-401-9975

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part 1 was open-label; Part 2 was double-blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2018
• First Posted: February 27, 2018
• Study Start: March 19, 2018
• Primary Completion: July 19, 2019
• Study Completion: July 19, 2019
• Last Updated: May 13, 2021
• Results First Posted: October 14, 2020

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)