SYNB1934 for Phenylketonuria

(SYNPHENY-3 Trial)

Recruiting at 21 trial locations

Overseen By Aneal Khan, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Synlogic

Must be taking: Sapropterin, Sepiapterin

Must not be taking: Palynziq, Systemic antibiotics

Disqualifiers: Pregnancy, DNAJC12 deficiency, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

35 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you continue your current diet, sapropterin, sepiapterin, and large neutral amino acids without changes during the study. However, you cannot take Palynziq® (pegvaliase-pqpz) within 1 month of screening or any systemic antibiotics within 28 days prior to the first dose.

What is the purpose of this trial?

This trial tests SYNB1934v1, a new treatment for people with high blood phenylalanine (Phe) levels. The goal is to find the best dose that reduces Phe levels by at least 20% without causing side effects.

Eligibility Criteria

Adults with Phenylketonuria (PKU) who haven't been able to control their blood Phe levels using current treatments can join. They should be on a stable diet and treatment for at least 1 month, agree to not change their diet or PKU management during the trial, and use contraception if applicable. Pregnant women, those on recent investigational drugs, antibiotics, or specific PKU therapies like Palynziq®, are excluded.

Inclusion Criteria

I am using birth control during and for 2 weeks after the study.

I can maintain my current diet and supplements throughout the study.

I have PKU and my blood Phe levels are too high despite current treatments.

Exclusion Criteria

Acute or chronic medical, surgical, psychiatric, or social condition or laboratory abnormality that may increase patient risk associated with study participation, compromise adherence to study procedures and requirements, and, in the judgment of the investigator, would make the patient inappropriate for enrollment

I am allergic to E. coli Nissle, SYNB1934v1 ingredients, or cinnamon and cannot tolerate certain acid-reducing medications.

I have received gene therapy for PKU.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-escalating, open-label period (DEP)

Participants receive escalating doses of SYNB1934v1 to determine an individually titrated dose (iTD)

Up to 15 weeks

Weekly visits for dose escalation and monitoring

Randomized withdrawal period (RWP)

Participants are randomized to receive SYNB1934v1 or placebo to assess efficacy and safety

4 weeks

Visits at Weeks 1, 3, and 4 for blood Phe level measurement

Open-label extension (OLE)

Participants may continue receiving SYNB1934v1 with dose adjustments based on tolerability

Up to 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• SYNB1934

Trial Overview The study tests SYNB1934v1's effectiveness in managing PKU over three parts: initial dose finding up to 15 weeks; a double-blind phase where participants randomly get either SYNB1934v1 or placebo for four weeks; followed by an open-label extension lasting up to three years.

Participant Groups

Group I: RWP (Part 2, SYNB1934v1) Experimental Treatment 1 Intervention

Participants who completed the DEP were randomized 1:1 to receive SYNB1934v1 at their iTD established in the DEP orally immediately after meals. Participants remained on this dose of SYNB1934v1 for the duration of the RWP; doses of SYNB1934v1 were not permitted to be modified during the RWP.

Group II: OLE (Part 3, SYNB1934v1) Experimental Treatment 1 Intervention

Participants completed a dose ramp to their iTD guided by tolerability, as described for the DEP, including the full dose-ramp schedule. The iTD in the OLE may have been different from the iTD in the DEP or RWP. The investigator may have escalated the dose of SYNB1934v1 up to 1 × 10\^12 live cells based on tolerability; multiple attempts to escalate to a higher dose level were permitted per investigator discretion.

Group III: DEP (Part 1, SYNB1934v1) Experimental Treatment 1 Intervention

Participants received SYNB1934v1 orally immediately after meals on the following dose-ramp regimen: Dose level 1 (Days 1-9): 3 × 10\^11 live cells partial dose up to 3 times daily (TID); Dose level 2 (Weeks 4-6): 6 × 10\^11 live cells up to TID; Dose level 3 (Weeks 7-9): 1 × 10\^12 live cells up to TID.

Group IV: RWP (Part 2, Placebo) Placebo Group 1 Intervention

Participants who completed the DEP were randomized 1:1 to receive placebo orally immediately after meals. Participants remained on the same dose of placebo for the duration of the RWP; doses of placebo were not permitted to be modified during the RWP.

Who Is Running the Clinical Trial?

Synlogic

Lead Sponsor

Trials

10

Recruited

460+