The open-label trial (NCT04534842), initially delayed due to the COVID-19 pandemic, seeks to enroll 12 adult patients who failed to respond, or did not tolerate, other PKU approved therapies, such as Kuvan (sapropterin dihydrochloride) or Palynziq (pegvaliase-pqpz).
Recruitment for the SynPheny-1 trial is underway at several clinical sites across the U.S. The company is planning to announce data from the trial in the coming months.
“It is also very important to know … that you can participate in this study at any time, in a virtual manner, using our available home healthcare services,” Andrew Marsh, head of development operations at Synlogic, said in a company webinar.
After being screened for eligibility, study participants will enter a six-day run-in period where they will be asked to follow a customized diet designed to control their intake of phenylalanine, the amino acid at excessively high levels in PKU patients due to the lack of an enzyme that normally breaks it down. Amino acids are protein building blocks.
Then, they will enter in the 15-day treatment period, where they will receive four gradually increasing oral doses of SYNB1618, up to three times daily with food. While receiving the experimental treatment, they will also be asked to continue following the same diet they had in the run-in period.
Around two weeks after completing the 15-day treatment, study participants will have a final follow-up study visit. Until then, they will have to continue recording their meal plans.
The study’s main goal is to assess the therapy’s effectiveness at lowering blood levels of phenylalanine. Additional goals include SYNB1618’s safety, which will be evaluated based on the incidence and severity of reported side effects.
The dosing strategy in SynPheny-1 was selected based on data from a previous bridging study, in which a solid oral formulation of SYNB1618 had a favorable safety profile and was able to break down phenylalanine in the gastrointestinal (GI) tract of healthy volunteers.
Originally developed as a liquid solution for oral intake, SYNB1618 contains genetically modified bacteria (E. coli Nissle) that can rapidly and easily degrade phenylalanine into non-toxic molecules.
These bacteria, which are considered probiotics, can do so by producing two enzymes — phenylalanine ammonia lyase and L-amino acid deaminase — that not only break down phenylalanine, but also influence its recycling between the GI tract and the blood.
Through this mechanism, SYNB1618 is expected to help normalize phenylalanine levels in all PKU patients, regardless of their age or disease subtype.
In addition to new data from SynPheny-1, Synlogic is expected to announce new findings from other clinical trials of SYNB8802 and SYNB1891, the company’s treatment candidates for enteric hyperoxaluria and some types of cancers, later this year.
“With three programs in clinical trials, multiple proof of concept opportunities, and a preclinical portfolio advancing rapidly towards the clinic, Synlogic is poised for success with a number of data readouts coming in 2021,” Aoife Brennan, MD, president and CEO of Synlogic, said in a press release.
“We enter 2021 with momentum and the opportunity to truly see the potential of novel Synthetic Biotic medicines to make a meaningful difference in patients’ lives,” she added.
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