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

Primary Purpose

Phenylketonuria

Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
CBT102-A capsule
Placebo capsule
Sponsored by
Children's Hospital of Fudan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Phenylketonuria

Eligibility Criteria

3 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Children's Hospital of Fudan UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

CBT102-A group

Placebo group

Arm Description

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

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

Outcomes

Primary Outcome Measures

Changes from Baseline in Blood Phe Concentration
This is a repeatedly measures outcome; Blood Phe concentration will be detected at baseline, administration(Day 1~Day 20), observation(Day 21~Day 23) and follow-up periods(Day 51); During the administraion time, Phe concentrations will be measured at 4 hours after each day on Day 4,Day 8, Day 12, Day 15, Day 18, Day 20; A drop of blood will be collected from the end of the finger on the filter paper and will be detected by tandem mass spectrometry.

Secondary Outcome Measures

Occurrence of Treatment-Emergent Adverse Events(TEAE)≥2 Grade
The grade of TEAE will be assessed according to Toxicity is graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0; TEAE ≥ 2 grade define as occurrence of age-appropriate limitations in instrumental activities of daily living; Adverse events require medical intervention.
Occurrence of TEAE
All treatment emerged adverse events during the whole study
Changing Value of Subjects Urinary Metabolites
This is a repeatedly measures outcome; During the administraion time, subjects' urine will be collected after each day on Day 8, Day 12, Day 20 and Day 23; The changes of metabolites will be detected by tandem mass spectrometry.
Changing Value of Subjects Fecal Metabolites
This is a repeatedly measures outcome; During the administraion time, subjects' fecal will be collected after each day on Day 8, Day 12, Day 20 and Day 23; The changes of metabolites will be detected by tandem mass spectrometry.
Clearance of CBT102-A from Fecal
This is a repeatedly measures outcome; CBT102-A transit through the gastrointestinal tract will be measured with fecal quantitative polymerase chain reaction (qPCR) assays from fecal samples collected at baseline,Day 20 and Day 23 during the dosing period; CBT102-A clearance reflects a test value of below the limit of quantitation (BLQ) occurring after the indicated number of days following the last dose of investigational product.

Full Information

First Posted
July 9, 2023
Last Updated
September 6, 2023
Sponsor
Children's Hospital of Fudan University
Collaborators
Hedu Biotechnology (Shanghai) Co., LTD
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1. Study Identification

Unique Protocol Identification Number
NCT05948020
Brief Title
Efficacy and Safety of Orally Administered Engineered Probiotics (CBT102-A) for the Treatment of Children With Phenylketonuria
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 2, 2023 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
March 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital of Fudan University
Collaborators
Hedu Biotechnology (Shanghai) Co., LTD

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Phenylketonuria

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
Masking to the investigation sites and subjects (including subjects' guardians)
Allocation
Randomized
Enrollment
15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CBT102-A group
Arm Type
Experimental
Arm Description
10 subjects receive oral CBT102-A with three meals per day for a total of 20 days
Arm Title
Placebo group
Arm Type
Placebo Comparator
Arm Description
5 subjects receive oral placebo with three meals per day for a total of 20 days
Intervention Type
Biological
Intervention Name(s)
CBT102-A capsule
Intervention Description
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
Other
Intervention Name(s)
Placebo capsule
Intervention Description
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).
Primary Outcome Measure Information:
Title
Changes from Baseline in Blood Phe Concentration
Description
This is a repeatedly measures outcome; Blood Phe concentration will be detected at baseline, administration(Day 1~Day 20), observation(Day 21~Day 23) and follow-up periods(Day 51); During the administraion time, Phe concentrations will be measured at 4 hours after each day on Day 4,Day 8, Day 12, Day 15, Day 18, Day 20; A drop of blood will be collected from the end of the finger on the filter paper and will be detected by tandem mass spectrometry.
Time Frame
From baseline to Day 51
Secondary Outcome Measure Information:
Title
Occurrence of Treatment-Emergent Adverse Events(TEAE)≥2 Grade
Description
The grade of TEAE will be assessed according to Toxicity is graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0; TEAE ≥ 2 grade define as occurrence of age-appropriate limitations in instrumental activities of daily living; Adverse events require medical intervention.
Time Frame
From baseline to Day 23
Title
Occurrence of TEAE
Description
All treatment emerged adverse events during the whole study
Time Frame
From baseline to Day 51
Title
Changing Value of Subjects Urinary Metabolites
Description
This is a repeatedly measures outcome; During the administraion time, subjects' urine will be collected after each day on Day 8, Day 12, Day 20 and Day 23; The changes of metabolites will be detected by tandem mass spectrometry.
Time Frame
From baseline to Day 23
Title
Changing Value of Subjects Fecal Metabolites
Description
This is a repeatedly measures outcome; During the administraion time, subjects' fecal will be collected after each day on Day 8, Day 12, Day 20 and Day 23; The changes of metabolites will be detected by tandem mass spectrometry.
Time Frame
From baseline to Day 23
Title
Clearance of CBT102-A from Fecal
Description
This is a repeatedly measures outcome; CBT102-A transit through the gastrointestinal tract will be measured with fecal quantitative polymerase chain reaction (qPCR) assays from fecal samples collected at baseline,Day 20 and Day 23 during the dosing period; CBT102-A clearance reflects a test value of below the limit of quantitation (BLQ) occurring after the indicated number of days following the last dose of investigational product.
Time Frame
From baseline to Day 23

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wenhao Zhou
Phone
8618017591123
Email
zhouwenhao@fudan.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Huijun Wang
Phone
8618017590813
Email
huijunwang@fudan.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wenhao Zhou
Organizational Affiliation
Children's Hospital of Fudan University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Huijun Wang
Organizational Affiliation
Children's Hospital of Fudan University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Haitao Zhu
Organizational Affiliation
Children's Hospital of Fudan University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Yajie Su
Organizational Affiliation
Children's Hospital of Fudan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital of Fudan University
City
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wenhao Zhou
Phone
8618017591123
Email
zhouwenhao@fudan.edu.cn
First Name & Middle Initial & Last Name & Degree
Huijun Wang
Phone
8618017590813
Email
huijunwang@fudan.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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