Efficacy and Safety of Orally Administered Engineered Probiotics (CBT102-A) for the Treatment of Children With Phenylketonuria

ABSTRACT

ConditionPhenylketonuria

InterventionBiological CBT102-A capsule;Other Placebo capsule

Primary outcome:Changes from Baseline in Blood Phe Concentration

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.