Synlogic Doses First Patient in Phase 1b/2a Trial of SYNB1020 for Treatment of Hyperammonemia in Patients with Cirrhosis
– First clinical trial of a Synthetic Biotic™Medicine in patients –
– Randomized, double-blind, placebo-controlled study evaluating safety and tolerability of SYNB1020 as primary endpoint; ammonia-lowering as secondary endpoint –
“Our recently reported Phase 1 trial of SYNB1020 demonstrated that this
Synthetic Biotic medicine was well tolerated and provided a
dose-dependent proof of mechanism, functioning as designed in healthy
volunteers. We look forward to evaluating the safety, tolerability and
therapeutic potential of SYNB1020 in patients with liver disease who
have developed cirrhosis,” said
Synthetic Biotic therapies are designed to function in the gastrointestinal tract to convert metabolites that can build up to toxic levels in the blood into harmless metabolites that can be excreted from the body. Elevated blood ammonia levels are toxic to the brain and can have severe consequences, including neurologic crises requiring hospitalization and resulting in irreversible cognitive damage and death. SYNB1020 is designed to consume ammonia and convert it to arginine, an amino acid.
About Synlogic’s Phase 1b/2a Trial of SYNB1020 in Patients with Cirrhosis
This Phase 1b/2a study has two parts:
First, an initial sentinel open-label cohort of subjects with cirrhosis and a Model for End-Stage Liver Disease (MELD) score < 12 will receive orally administered SYNB1020 (5 x 1011 CFU TID) for six days. Subjects will be admitted to an inpatient facility for a run-in diet, baseline assessments, safety monitoring, and collection of blood, urine, and fecal samples for the evaluation of safety, tolerability, pharmacokinetics and pharmacodynamics of treatment. Once safety and tolerability have been established in these subjects, enrollment will be opened to subjects in Part 2.
Part 2 of the trial comprises a randomized, double-blinded, placebo-controlled study in patients with cirrhosis and hyperammonemia. Eligible subjects will be admitted to an inpatient facility for a run-in diet and 24-hour ammonia profile, and those with an elevated ammonia level will proceed with randomization and receive either placebo or orally administered SYNB1020 (5 x 1011 CFU TID) for six days. The primary endpoint of the study is safety and tolerability. In addition, the study will evaluate the effect of SYNB1020 administration on plasma ammonia levels as well as other exploratory endpoints.
Hyperammonemia is a metabolic condition characterized by an excess of ammonia in the blood. In healthy individuals, ammonia is primarily produced in the intestine as a byproduct of protein metabolism and microbial degradation of nitrogen-containing compounds. Ammonia is then converted to urea in the liver and is excreted in urine. However, if the liver’s ability to convert ammonia to urea is compromised, either due to a genetic defect such as UCDs or acquired liver disease that leads to cirrhosis, ammonia accumulates in the blood. Elevated blood ammonia levels are toxic to the brain and can have severe consequences, including neurologic crises requiring hospitalization, irreversible cognitive damage and death.
About Synthetic Biotic Medicines
Synlogic’s innovative new class of Synthetic Biotic medicines leverages
the tools and principles of synthetic biology to genetically engineer
probiotic microbes to perform or deliver critical functions missing or
damaged due to disease. The company’s two lead programs, SYNB1020 and
SYNB1618, target hyperammonemia as a result of liver damage or genetic
disease, and phenylketonuria, respectively. Patients with these diseases
are unable to break down commonly occurring by-products of digestion
that then accumulate to toxic levels and cause serious health
consequences. When delivered orally, Synthetic Biotic medicines can act
from the gut to compensate for the dysfunctional metabolic pathway and
have a systemic effect, with the potential to significantly improve
symptoms of disease for affected patients.
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