SYNB1934 for Phenylketonuria

(SYNPHENY-3 Trial)

No longer recruiting at 23 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called SYNB1934 for individuals with phenylketonuria (PKU), a condition where the body cannot break down the amino acid phenylalanine, leading to harmful blood levels. The trial aims to determine if SYNB1934 can manage these levels more effectively than current treatments. Individuals with PKU who struggle to control their blood phenylalanine levels, despite a strict diet and existing medications, might be suitable candidates for this trial. Participants will take SYNB1934 with meals, and the trial includes several phases to monitor effects and any side effects over time. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for PKU.

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.

Is there any evidence suggesting that SYNB1934 is likely to be safe for humans?

Research has shown that SYNB1934 has generally been well-tolerated in past studies. For example, one study found that participants taking SYNB1934 experienced significant reductions in phenylalanine levels, which is crucial for treating phenylketonuria (PKU). Although the study did not provide detailed safety information, the progression to later trial stages suggests a reasonable safety profile so far.

Additionally, early research reports have not identified any major side effects, supporting its continued testing in clinical trials. However, as with any new treatment, researchers will continue to monitor for side effects as more information becomes available. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

SYNB1934 is unique because it’s a living medicine specifically designed for phenylketonuria (PKU), a condition where the body can’t properly break down the amino acid phenylalanine. Unlike traditional treatments like dietary management or enzyme replacement therapies, SYNB1934 uses live bacteria to naturally consume phenylalanine in the gut before it enters the bloodstream. This innovative approach could offer more flexibility and effectiveness in managing PKU, potentially reducing the strict dietary restrictions currently necessary for patients. Researchers are excited because it represents a new way of tackling PKU by directly addressing phenylalanine levels with a biological approach.

What evidence suggests that SYNB1934 might be an effective treatment for phenylketonuria?

Research has shown that SYNB1934, which participants in this trial may receive, produces promising results in lowering phenylalanine levels in people with phenylketonuria (PKU). In earlier studies, 60% of patients responded well, experiencing a 42% drop in phenylalanine levels. This treatment uses a specially modified type of bacteria to help break down phenylalanine, a problematic amino acid for people with PKU. SYNB1934 has also demonstrated better efficacy than previous treatments like SYNB1618. These findings suggest that SYNB1934 could effectively manage PKU. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05764239

Efficacy and Safety of SYNB1934 in Patients With PKU ...

A Phase 3, Double-blind, Placebo-controlled, Randomized Withdrawal Study to Evaluate the Efficacy and Safety of SYNB1934 in Patients With PKU (SYNPHENY-3).

2.

investor.synlogictx.com

investor.synlogictx.com/news-releases/news-release-details/synlogic-announces-positive-top-line-phase-2-data

Synlogic Announces Positive Top-Line Phase 2 Data for ...

Positive results include clinically meaningful Phe reductions, with a 60% response rate and 42% reduction in plasma Phe among responders across the study ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8553829/

Improvement of a synthetic live bacterial therapeutic for ...

A candidate PAL variant was used to construct a second-generation PKU therapeutic strain, SYNB1934, which was shown to outperform SYNB1618 in ...

4.

clinicaltrials.eu

clinicaltrials.eu/trial/study-on-the-effectiveness-and-safety-of-synb1934-for-adults-with-phenylketonuria-pku/

Study on the Effectiveness and Safety of SYNB1934 ...

This clinical trial evaluates the safety and efficacy of the active substance SYNB1934v1, a modified strain of Escherichia coli, in reducing phenylalanine ...

5.

clinicaltrialsarena.com

clinicaltrialsarena.com/news/synlogic-synb1934-trial/

Synlogic begins Phase III trial of SYNB1934 for ...

US-based biotechnology firm Synlogic has begun a Phase III trial of SYNB1934 for the treatment of phenylketonuria (PKU), a rare metabolic disease.

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04534842

Efficacy and Safety of SYNB1618 and SYNB1934 in Adult ...

This Phase 2 study in patients with phenylketonuria (PKU) will be an open-label, dual-arm study of either a SYNB1618 or SYNB1934 dose-ramp regimen.