Synlogic has begun dosing healthy volunteers in a Phase I clinical trial of SYNB1020 for the treatment of hyperammonemia associated with diseases such as urea cycle disorders (UCD) and hepatic encephalopathy (HE).
SYNB1020 belongs to the company’s new class of medicines known as Synthetic Biotic, and is developed using synthetic biology for genetically re-engineering probiotic microbes to perform important functions in the body that are missing or damaged by the disease.
The two-part, randomised, double-blinded, dose-escalating, placebo-controlled Phase I trial is designed to evaluate the safety and tolerability of the product in 50 subjects.
Synlogic president and CEO Jose Carlos Gutierrez-Ramos said: “SYNB1020 has been designed to deliver a complementary metabolic pathway in the gut with the intended consequence of removing excess ammonia in the blood, essentially replacing what a patient cannot do with his or her liver.
“We believe this novel approach could change the treatment paradigm for patients suffering from these devastating conditions.”
The first part of the trial will include a single-ascending dose (SAD) in healthy subjects across multiple-dose cohorts to determine the maximum tolerated dose (MTD) within the single dose-range used.
In an inpatient setting, the second part will study multiple-ascending doses (MAD) in various dose cohorts, which were validated as tolerable in the first part.
The trial’s primary outcome is the examination of nature and frequency of adverse events (AEs), laboratory assessments and electrocardiogram (ECG), while the secondary outcome includes a measure of SYNB1020’s gastrointestinal (GI) tolerability and kinetics.
The firm intends to further study SYNB1020 in two other clinical trials set to be initiated by mid next year in symptomatic UCD and HE patients with increased toxic ammonia levels.