Engineered probiotics for treating children with phenylketonuria

Efficacy and Safety of Orally Administered Engineered Probiotics (CBT102-A) for the Treatment of Children With Phenylketonuria：a Randomized, Double-blind, Placebo-controlled, Parallel-group Clinical Study

This study is testing a new engineered probiotic to see if it can help children with phenylketonuria lower their blood phenylalanine levels.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 3 Years to 17 Years
• Sex: All
• Sponsor: Children's Hospital of Fudan University (Academic / other)
• Locations: 1 site (Shanghai)
• Trial ID: NCT05948020 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of CBT102-A, an engineered probiotic, in treating children aged 3 to 17 years with phenylketonuria (PKU). The study is randomized, double-blind, and placebo-controlled, involving 15 participants who will be assigned to either the experimental group receiving CBT102-A or a control group receiving a placebo for 20 days. The primary goal is to assess the reduction of blood phenylalanine levels and monitor any treatment-emergent adverse events. Participants will be followed up weekly for four weeks after the intervention to ensure comprehensive safety and efficacy data collection.

Who should consider this trial

Good fit: Ideal candidates are children aged 3 to 17 years with a confirmed diagnosis of phenylketonuria and elevated blood phenylalanine levels.

Not a fit: Patients who do not have phenylketonuria or whose blood phenylalanine levels are not elevated will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly lower blood phenylalanine levels in children with PKU, potentially improving their cognitive outcomes.

How similar studies have performed: While engineered probiotics are a novel approach, preliminary animal studies have shown promising results, indicating potential for success in human trials.

Eligibility criteria

Inclusion Criteria:

* Blood phe ≥ 600μmol/L at newborn screening;
* Blood phe ≥ 600μmol/L at least 3 times in the last 1 year before screening, and the blood Phe ≥ 600μmol/L in the last 1 time;
* Screening laboratory evaluations (e.g., chemistry panel, complete blood count, urinalysis, creatinine clearance, CRP) within normal limits or judged to be not clinically significant by the investigator;
* Stable diet for at least 60 days prior to screening;
* Able to produce at least 2 bowel movements per week on average without using any form of laxatives;
* Adolescents and children's guardians can voluntarily complete the whole process of informed consent, including stool, urine and blood collection, adherence to diet control, hospital monitoring, follow-up and oral trial drug compliance, and sign informed consent.

Exclusion Criteria:

* The standard percentile values of height and weight of Chinese children aged 0 to 18 years were evaluated with weight less than P3 or weight greater than P97；
* History of active or chronic passage of 3 or more loose stools per day；
* Have any medical conditions or medications that may affect the absorption of medications or nutrients；
* History of or current immunodeficiency disorder including autoimmune disorders；
* Subjects with obvious influenza-like symptoms caused by COVID-19 or other viral infections during screening；
* Hepatitis B surface antigen and/or hepatitis C antibodies and/or treponema pallidum antibodies positive；
* Subjects who are dependent on drugs and alcohol；
* Received gene therapy related to PKU；
* Intolerant or allergic to Escherichia coli Nissle 1917 (EcN)；
* Active gastrointestinal bleeding or a proven history of gastrointestinal bleeding within 60 days prior to screening；
* Antibiotics within 28 days before the planned first dose of investigational product (IP), or anticipated during the study period；
* Take probiotic supplements within 28 days before the planned first dose of IP, or anticipated during the study period；
* A history of fever, confirmed bacteremia, or other active infection within 30 days prior to the planned first dose of IP；
* Drugs that use of the digestive system has been used within 30 days prior to the planned first dose of IP;
* Drugs that may affect gastrointestinal function has been used within 30 days prior to the planned first dose of IP;
* Major survery performed within 90 days before the anticipated first dose of IP or planned surgery or hospitalization during the study period；
* Take sapropterin (KUVAN®) within 1 week before the planned first dose of IP；
* Use pegylated recombinant phenylalanine ammonia lyase (PALYNZIQ™) within 30 days before the planned first dose of IP；
* History of severe immune adverse reactions to PALYZIQ；
* Participated in an interventional clinical trial and used the investigational drug within 60 days or 5 half-lives before the planned first dose of IP；
* Subjects who may not be able to complete the study for other reasons.

Where this trial is running

Shanghai

• Children's Hospital of Fudan University — Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Wenhao Zhou — Children's Hospital of Fudan University
• Study coordinator: Wenhao Zhou

Conditions Phenylketonuria