Back to resultsRecombinant Adeno-associated Virus Administration for Patients With Menkes Syndrome
Primary Purpose
Menkes Syndrome
Status
Terminated
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
Recombinant adeno-associated virus administration
Sponsored by
About this trial
This is an interventional treatment trial for Menkes Syndrome focused on measuring gene therpy, adeno-associated virus
Eligibility Criteria
Inclusion Criteria:
- The definitive diagnosis of Menkes disease is determined by molecular genetic confirmation of ATP7A mutations.
- Disorder of copper metabolism with the serum copper < 50 ug/dl (reference 70-180 ug/dl) and ceruloplasmin < 20 mg/dl (reference 20-45 mg/dl) in the absence of copper supplement injection.
- Clinical onsets of developmental retardation, seizures, and hypotonia with delay in poor head control and inability to sit at the age of 2-3 months.
- willingness to complete the informed consent process and to comply with study procedures and visit schedule.
- willingness to agree with the demand of nasal or gastrostomy feeding for nutrition maintenance in the opinion of the investigator.
Exclusion Criteria:
- Inability to be accepted for delivering the Investigational medical product due to failure to recover from severe or acute diseases.
- Presence of specific anti-AAV antibodies.
- Active viral infection (includes HIV, COVID-19, or serology positive for hepatitis B or C).
- Allergy to the substance or excipients in the Investigational medical product solution.
- Previous or current participation in any other gene therapies.
- Severe abnormality of hepatic, renal, and cardiac function.
Sites / Locations
- Kunming Hope of Health Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
A single-arm study of recombinant adeno-associated virus
Arm Description
An open, single-arm study of recombinant adeno-associated virus
Outcomes
Primary Outcome Measures
Monitoring the disease course or vital signs to assess the efficacy of the investigational medical product
Based on studies of the natural history of Menkes syndrome, which shows that patients have a life span of fewer than three years, this study will evaluate the endpoint of life of patients with the investigational medical product infusion. The endpoint of life is defined as death or the need for ventilatory support (device dependence of at least 16 hours per day for more than 14 days).
Incidence of adverse events(AE) after the investigational medical product infusion
The frequency, severity, and laboratory findings of all adverse events/serious adverse events are included. Description, time, classification, and outcome of AE events resulted from the investigational medical product, delivery method, or emergency measures will be recorded in the case report form.
Secondary Outcome Measures
Developmental behavior assessment
CHOP INTEND was developed to be used on children from 3 months to over four years, although it is not limited to this age range. It was developed by looking at babies with SMA Type 1 and infants with other similar conditions, such as Menkes syndrome. There are 16 parts, and the scale scores infants on how well they can perform certain movements or what the physiotherapist sees while watching the child. Each one is scored from 0 to 4, with 0 being no response/ability to perform the movement and 4 being 'complete response' (being able to perform the task). The total possible score is 64.
The Developmental Behavior Scale for Children aged 0-6 years (WS/T 580-2017) released by the Ministry of Health of China is used to monitor and evaluate the development improvement of patients in gross motor, fine motor, language, adaptive ability, and social behavior. The scale applies to children aged 0-6 years, with 8-10 test items in each group, totaling 261.
Weight
Record weight of patients in kilograms
Height
Record height of patients in meters
Head circumference
Record head circumference of patients in centimeters
Full Information
NCT ID
NCT05507996
First Posted
August 15, 2022
Last Updated
November 27, 2022
Sponsor
Kunming Hope of Health Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05507996
Brief Title
Recombinant Adeno-associated Virus Administration for Patients With Menkes Syndrome
Official Title
An Investigator-initiated Trial Evaluating the Efficacy and Safety of Recombinant Adeno-associated Virus Administration in Patients With Menkes Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Terminated
Why Stopped
The PI decides to stop.
Study Start Date
August 18, 2022 (Actual)
Primary Completion Date
November 23, 2022 (Actual)
Study Completion Date
November 23, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kunming Hope of Health Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
It is a single-center, open, single-arm, non-randomized investigator-initiated trial evaluating the efficacy and safety of recombinant adeno-associated virus administration for patients with Menkes syndrome.
Detailed Description
Who can participate? Patients with Menkes syndrome were diagnosed by combining clinical and genetic diagnoses.
How to conduct this study? In this study, the constructed recombinant adeno-associated virus preparation will be delivered to patients with Menkes syndrome. After administration, close follow-up will be conducted for at least three months, followed by regular follow-up until at least the 12th month. The efficacy and safety of treatment will be observed and evaluated. After the completion of the study, participants will decide whether to participate in the long-term follow-up program for five years.
What are the possible benefits and risks of participating? Benefits: This study may prolong the life span and improve the prognosis of Menkes syndrome subjects. The information obtained from this study will help determine what treatment may be safe and effective for other subjects with similar conditions.
Risks: Subjects may have adverse reactions to the treatment. These adverse reactions may include abnormal liver injury, fever, thrombocytopenia, thrombotic microangiopathy, and possibly others.
Where is the study run? Kunming Hope of Health Hospital.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Menkes Syndrome
Keywords
gene therpy, adeno-associated virus
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A single-arm study of recombinant adeno-associated virus
Arm Type
Experimental
Arm Description
An open, single-arm study of recombinant adeno-associated virus
Intervention Type
Drug
Intervention Name(s)
Recombinant adeno-associated virus administration
Intervention Description
The investigational medical product will be injected from 1E12 GC/kg to 1E14 GC/kg.
Primary Outcome Measure Information:
Title
Monitoring the disease course or vital signs to assess the efficacy of the investigational medical product
Description
Based on studies of the natural history of Menkes syndrome, which shows that patients have a life span of fewer than three years, this study will evaluate the endpoint of life of patients with the investigational medical product infusion. The endpoint of life is defined as death or the need for ventilatory support (device dependence of at least 16 hours per day for more than 14 days).
Time Frame
Up to the end of life after infusion or 12 months after the age of 3 years
Title
Incidence of adverse events(AE) after the investigational medical product infusion
Description
The frequency, severity, and laboratory findings of all adverse events/serious adverse events are included. Description, time, classification, and outcome of AE events resulted from the investigational medical product, delivery method, or emergency measures will be recorded in the case report form.
Time Frame
Up to 12 months after the investigational medical product infusion
Secondary Outcome Measure Information:
Title
Developmental behavior assessment
Description
CHOP INTEND was developed to be used on children from 3 months to over four years, although it is not limited to this age range. It was developed by looking at babies with SMA Type 1 and infants with other similar conditions, such as Menkes syndrome. There are 16 parts, and the scale scores infants on how well they can perform certain movements or what the physiotherapist sees while watching the child. Each one is scored from 0 to 4, with 0 being no response/ability to perform the movement and 4 being 'complete response' (being able to perform the task). The total possible score is 64.
The Developmental Behavior Scale for Children aged 0-6 years (WS/T 580-2017) released by the Ministry of Health of China is used to monitor and evaluate the development improvement of patients in gross motor, fine motor, language, adaptive ability, and social behavior. The scale applies to children aged 0-6 years, with 8-10 test items in each group, totaling 261.
Time Frame
At baseline and 3, 6, 9, 12 months after infusion
Title
Weight
Description
Record weight of patients in kilograms
Time Frame
At baseline and 3, 6, 9, 12 months after infusion
Title
Height
Description
Record height of patients in meters
Time Frame
At baseline and 3, 6, 9, 12 months after infusion
Title
Head circumference
Description
Record head circumference of patients in centimeters
Time Frame
At baseline and 3, 6, 9, 12 months after infusion
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
The definitive diagnosis of Menkes disease is determined by molecular genetic confirmation of ATP7A mutations.
Disorder of copper metabolism with the serum copper < 50 ug/dl (reference 70-180 ug/dl) and ceruloplasmin < 20 mg/dl (reference 20-45 mg/dl) in the absence of copper supplement injection.
Clinical onsets of developmental retardation, seizures, and hypotonia with delay in poor head control and inability to sit at the age of 2-3 months.
willingness to complete the informed consent process and to comply with study procedures and visit schedule.
willingness to agree with the demand of nasal or gastrostomy feeding for nutrition maintenance in the opinion of the investigator.
Exclusion Criteria:
Inability to be accepted for delivering the Investigational medical product due to failure to recover from severe or acute diseases.
Presence of specific anti-AAV antibodies.
Active viral infection (includes HIV, COVID-19, or serology positive for hepatitis B or C).
Allergy to the substance or excipients in the Investigational medical product solution.
Previous or current participation in any other gene therapies.
Severe abnormality of hepatic, renal, and cardiac function.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Li Li
Organizational Affiliation
Kunming Hope of Health Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kunming Hope of Health Hospital
City
Kunming
State/Province
Yunnan
ZIP/Postal Code
650000
Country
China
12. IPD Sharing Statement
Learn more about this trial
Recombinant Adeno-associated Virus Administration for Patients With Menkes Syndrome
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