In the DEP, all enrolled participants will maintain a stable diet reflecting their baseline Phe intake and receive escalating doses of SYNB1934v1 from approximately 3 to 15 weeks to determine an individually titrated dose (iTD), which is defined as the highest dose the patient is able to tolerate.~Participants who complete the DEP at their iTD for at least 3 weeks will enter a 4-week RWP. Participants will be randomized 1:1 to receive SYNB1934v1 at their iTD determined in the DEP or placebo 3 times daily (TID).~Participants who complete the 4-week RWP may enter the OLE and receive SYNB1934v1 for up to 36 months.~The primary determination of efficacy will be based on the comparison of SYNB1934v1 versus placebo in the RWP. Safety will be evaluated by scheduled monitoring of adverse events, vital signs, and clinical laboratory measurements.
This is a 3-part, adaptive study consisting of a dose-escalating period (DEP) of up to 15 weeks (Part 1), followed by a 4-week, double-blind, placebo-controlled randomized withdrawal period (RWP) (Part 2), and an open-label extension (OLE) (Part 3) of up to 36 months.