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

NCT ID: NCT05948020

Last Updated: 2023-09-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-02
• Study Completion Date: 2024-03-31

Brief Summary

This is a randomized, double-blind, placebo-controlled, parallel-group study. A total of 15 children with phenylketonuria(PKU) age 3 to 17 years will be randomized to two groups. Experimental group of 10 children will intervene engineered probiotics (CBT102-A) for 20 days and 5 children will intervene placebo. The goal of this study is to determine whether CBT102-A is an effective and safe treatment for PKU.

Detailed Description

Due to an increased blood phenylalanine (Phe) concentration, untreated children with PKU will develop progressively intellectual disability. Engineered probiotics can metabolize Phe into other products in the intestine by expressing related exogenous proteins in the Phe metabolic pathway, thereby reducing Phe concentration in the intestine and blood.

Animal experiments have confirmed the efficacy and safety of CBT102-A. This study will enroll children with PKU age 3 to 17 years according to a strict inclusion and exclusion criteria. Subjects who meet the requirements will be randomly assigned on Day 1 and start the study administration. The administration period of both groups is 20 days (Day 1~Day 20), in which the experimental group receives CBT102-A with 4 dose levels, and the control group receives placebo administration, with the same mode, frequency, time, cycle and dose as the experimental group. All subjects will be observed for 3 days (Day 21~Day 23) without intervene in hospital and will be followed up weekly for 4 consecutive weeks after discharge（Day 51）.

Change of blood Phe concentration and occurrence of Treatment-Emergent Adverse Events(TEAE) with PKU will be used to evaluate the efficacy and safety of the CBT102-A.

Conditions

Phenylketonuria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

CBT102-A group

10 subjects receive oral CBT102-A with three meals per day for a total of 20 days

Group Type: EXPERIMENTAL

CBT102-A capsule

Intervention Type: BIOLOGICAL

Orally CBT102-A will be supplied by CommBio Therapeutics. It is an enteric-coated capsule with 1.25×10^11 live cell. The shelf life is 6 months.

Subjects receive oral dose of 1 capsule CBT102-A (1.25 x 10^11 live cell) before three meals per day on Day 1 to Day 4; Subjects receive oral dose of 2 capsule CBT102-A (2.5 x 10^11 live cell) before three meals per day on Day 5 to Day 8; Subjects receive oral dose of 4 capsule CBT102-A (5 x 10^11 live cell) before three meals per day on Day 9 to Day 12; Subjects receive oral dose of 8 capsule CBT102-A (1 x 10^12 live cell) before three meals per day on Day 13 to Day 20; All subjects will be observed for 3 days (Day 21~Day 23) without intervene in hospital and will be followed up weekly for 4 consecutive weeks after discharge（Day 51）.

Placebo group

5 subjects receive oral placebo with three meals per day for a total of 20 days

Group Type: PLACEBO_COMPARATOR

Placebo capsule

Intervention Type: OTHER

Orally placebo will be supplied by CommBio Therapeutics. It is an enteric-coated capsule with Lactose powder filler. The shelf life is 6 months. The color, condition, smell and other appearances are exactly the same as CBT102-A.

Subjects receive oral dose of 1 capsule placebo before three meals per day on Day 1 to Day 4; Subjects receive oral dose of 2 capsule placebo before three meals per day on Day 5 to Day 8; Subjects receive oral dose of 4 capsule placebo before three meals per day on Day 9 to Day 12; Subjects receive oral dose of 8 capsule placebo before three meals per day on Day 13 to Day 20; All subjects will be observed for 3 days (Day 21~Day 23) without intervene in hospital and will be followed up weekly for 4 consecutive weeks after discharge（Day 51）.

Interventions

CBT102-A capsule

Orally CBT102-A will be supplied by CommBio Therapeutics. It is an enteric-coated capsule with 1.25×10^11 live cell. The shelf life is 6 months.

Subjects receive oral dose of 1 capsule CBT102-A (1.25 x 10^11 live cell) before three meals per day on Day 1 to Day 4; Subjects receive oral dose of 2 capsule CBT102-A (2.5 x 10^11 live cell) before three meals per day on Day 5 to Day 8; Subjects receive oral dose of 4 capsule CBT102-A (5 x 10^11 live cell) before three meals per day on Day 9 to Day 12; Subjects receive oral dose of 8 capsule CBT102-A (1 x 10^12 live cell) before three meals per day on Day 13 to Day 20; All subjects will be observed for 3 days (Day 21~Day 23) without intervene in hospital and will be followed up weekly for 4 consecutive weeks after discharge（Day 51）.

Intervention Type: BIOLOGICAL

Placebo capsule

Orally placebo will be supplied by CommBio Therapeutics. It is an enteric-coated capsule with Lactose powder filler. The shelf life is 6 months. The color, condition, smell and other appearances are exactly the same as CBT102-A.

Subjects receive oral dose of 1 capsule placebo before three meals per day on Day 1 to Day 4; Subjects receive oral dose of 2 capsule placebo before three meals per day on Day 5 to Day 8; Subjects receive oral dose of 4 capsule placebo before three meals per day on Day 9 to Day 12; Subjects receive oral dose of 8 capsule placebo before three meals per day on Day 13 to Day 20; All subjects will be observed for 3 days (Day 21~Day 23) without intervene in hospital and will be followed up weekly for 4 consecutive weeks after discharge（Day 51）.

Intervention Type: OTHER

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.

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hedu Biotechnology (Shanghai) Co., LTD

UNKNOWN

Sponsor Role: collaborator

Children's Hospital of Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wenhao Zhou

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Fudan University

Huijun Wang

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Fudan University

Haitao Zhu

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Fudan University

Yajie Su

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Fudan University

Locations

Children's Hospital of Fudan University

Shanghai, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Wenhao Zhou

Role: CONTACT

zhouwenhao@fudan.edu.cn

8618017591123

Huijun Wang

Role: CONTACT

huijunwang@fudan.edu.cn

8618017590813

Facility Contacts

Wenhao Zhou

Role: primary

zhouwenhao@fudan.edu.cn

8618017591123

Huijun Wang

Role: backup

huijunwang@fudan.edu.cn

8618017590813

Other Identifiers

CBT-102

Identifier Type: -

Identifier Source: org_study_id