In short
This article discusses a Phase 3 clinical trial investigating the effectiveness and safety of SYNB1934, a novel treatment for Phenylketonuria (PKU). The study, named SYNPHENY-3, aims to assess how well SYNB1934 can reduce blood phenylalanine levels in adults with PKU who have not achieved recommended levels with existing treatments. The trial consists of three parts: a dose escalation period, a randomized withdrawal period, and an open-label extension, providing comprehensive data on the drug's potential benefits and safety profile.
At a glance
- Study Name
- SYNPHENY-3
- Phase
- Phase 3
- Drug
- SYNB1934 (genetically engineered E. coli Nissle 1917)
- Condition
- Phenylketonuria (PKU)
- Primary Objective
- Assess change in blood phenylalanine levels
- Study Design
- 3 parts: Dose Escalation, Randomized Withdrawal, Open-Label Extension
- Duration
- Up to 36 months (varies by participant)
- Key Inclusion Criteria
- Adults with PKU, blood Phe > 360 μmol/L despite current treatment
- Key Exclusion Criteria
- Current Palynziq use, certain medical conditions, antibiotic use, pregnancy
- Primary Endpoints
- Percent change in blood Phe, safety and tolerability
What is SYNB1934?
SYNB1934 is an innovative medication being developed to treat Phenylketonuria (PKU), a rare genetic disorder that affects the body's ability to process an amino acid called phenylalanine. The full name of this treatment is quite complex: "ESCHERICHIA COLI, STRAIN NISSLE 1917, EXPRESSING HIGH AFFINITY PHENYLALANINE TRANSPORTER, MODIFIED PHENYLALANINE AMMONIA LYASE (S92G, H133M, I167K, L432I, V470A) AND L-AMINO ACID DEAMINASE." For simplicity, it's referred to as SYNB1934 or SYNB1934v1 in clinical trials.
How Does SYNB1934 Work?
SYNB1934 is a genetically engineered strain of Escherichia coli Nissle 1917, a type of beneficial bacteria. It has been modified to express specific enzymes and transporters that can help break down phenylalanine in the gut. This approach aims to reduce the levels of phenylalanine in the blood of people with PKU, potentially allowing them to have a less restricted diet and better manage their condition.
Clinical Trial Overview
A Phase 3 clinical trial, called SYNPHENY-3, is currently underway to evaluate the effectiveness and safety of SYNB1934 in adults with PKU. This trial is designed to: Assess how SYNB1934 affects blood phenylalanine levels Determine the optimal dose for each participant Evaluate the safety and tolerability of the treatment Investigate how SYNB1934 might impact dietary protein intake
Who Can Participate in the Trial?
The trial is primarily focused on adults (18 years and older) with PKU who have difficulty maintaining recommended blood phenylalanine levels with current treatments. Some key eligibility criteria include: Diagnosis of PKU with uncontrolled blood phenylalanine levels (>360 μmol/L) despite current therapy Stable diet for at least 1 month prior to screening If using certain medications (sapropterin or sepiapterin), must be on a stable dose for at least 3 months Not currently taking Palynziq® (pegvaliase-pqpz) or having received gene therapy for PKU
Trial Structure
The SYNPHENY-3 trial is divided into three main parts: Dose Escalating, Open-Label Period (DEP): Participants receive increasing doses of SYNB1934 to determine their individually tolerated dose (iTD). Randomized Withdrawal Period (RWP): Participants are randomly assigned to continue SYNB1934 at their iTD or receive a placebo for 4 weeks. Open-Label Extension (OLE): Participants can receive SYNB1934 for up to 36 months, with potential adjustments to dosing and diet.
Potential Benefits of SYNB1934
If successful, SYNB1934 could offer several benefits for people with PKU: Reduction in blood phenylalanine levels Potential for less restrictive diets Improved management of PKU symptoms An alternative treatment option for those who don't respond well to existing therapies
Safety Considerations
As with any clinical trial, safety is a top priority. The study is closely monitoring: Adverse events and their severity Changes in clinical laboratory parameters Changes in vital signs Participants are carefully screened for any conditions that might increase their risk during the trial.