NCT03447730

Safety, Tolerability and Pharmacodynamics of SYNB1020

A Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability, and Pharmacodynamics of SYNB1020 in Hepatic Insufficiency and Cirrhosis Patients

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: Synlogic · Industry
• Sex: All
• Age: 18 Years – 74 Years
• Healthy volunteers: Not accepted

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.

Detailed description

In Part 1, a sentinel open-label cohort of subjects with cirrhosis and Model for End-Stage Liver Disease (MELD) score \<12 was admitted to an inpatient facility for a run-in diet, baseline assessments, IMP administration, safety monitoring, and collection of blood, urine, and stool samples for evaluation of safety, tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD) evaluations. Subjects in Part 1 were enrolled sequentially to receive SYNB1020. Once the safety and tolerability were established in Part 1, enrollment was opened to subjects in Part 2. Part 2 comprised a randomized, double-blind, placebo-controlled study in subjects with cirrhosis and hyperammonemia. Subjects were permitted to be pre-screened for eligibility based on medical history and a single fasting spot venous ammonia measurement. Eligible subjects with elevated fasting spot venous ammonia then underwent full screening within 7 days of pre-screening. Eligible subjects were admitted to an inpatient facility for a run-in diet and 24-hour ammonia profile, and those with an elevated 24-hour ammonia area under the curve (AUC) (\>1.2 × the upper limit of normal \[ULN\]) proceeded with computer-generated randomization in a 1:1 ratio to receive either SYNB1020 or matching placebo. Randomization was followed by IMP administration, safety monitoring, and collection of blood, urine, and stool samples for PK and PD evaluations.

Conditions

• Cirrhosis

Interventions

Type	Name	Description
DRUG	SYNB1020	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.
OTHER	Placebo	Subjects received placebo orally in a chilled buffered solution (100 mL).

Timeline

• Start date: 2018-03-19
• Primary completion: 2019-07-19
• Completion: 2019-07-19
• First posted: 2018-02-27
• Last updated: 2021-05-13
• Results posted: 2020-10-14

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study