Back to resultsLentiviral Gene Therapy for CGD
Primary Purpose
Chronic Granulomatous Disease
Status
Unknown status
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Infusion of lentiviral TYF-CGD-modified autologous stem cells
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Granulomatous Disease focused on measuring Chronic granulomatous disease, Lentiviral vector
Eligibility Criteria
Inclusion Criteria:
- CGD patients >= 0 years of age
- Molecular diagnosis confirmed by DNA sequencing and supported by laboratory evidence for absent or significantly reduced biochemical activities of the NADPH-oxidase
- Karnofsky-Index > =70%
- At least one prior, ongoing or refractory severe infection and/or inflammatory complications requiring hospitalization despite drug intervention
- Written informed consent for adult patient, and assent for pediatric subjects seven years or older
Exclusion Criteria:
- Contraindication for leukapheresis (anaemia Hb <8g/dl, cardiovascular instability, severe coagulopathy) or for administration of conditioning medication
- Female patients who are pregnant or lactating as determined by history and/or positive pregnancy test
Sites / Locations
- Shenzhen Geno-immune Medical InstituteRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Lentiviral TYF-CGD-modified autologous stem cells
Arm Description
Autologous hematopoietic stem cells transduced with lentiviral TYF vector carrying the functional gene
Outcomes
Primary Outcome Measures
Overall survival
Patient will be monitored for overall health condition, including immune cell assessments, blood biochemistry and metabolitic activities, metabolic detoxification.
Gene marking in bone marrow cells
Gene-modified cells in the bone marrow will be measured by vector-specific quantitative PCR of colony-forming cells. Patient overall survival will be followed up for 15 years.
Secondary Outcome Measures
Change in infection frequency
Recovery of immune function
Whole blood cell counts (WBC), including CD3+ CD4, CD8 T cells, CD19+ B cells and CD16/CD56 NK cells, and absolute neutrophil counts (ANC), the percentage of NADPH oxidase positive cells, and the kinetics of transduced cells as determined by dihydrorhodamine (DHR) assay, will be measured.
Full Information
NCT ID
NCT03645486
First Posted
July 24, 2018
Last Updated
September 18, 2019
Sponsor
Shenzhen Geno-Immune Medical Institute
1. Study Identification
Unique Protocol Identification Number
NCT03645486
Brief Title
Lentiviral Gene Therapy for CGD
Official Title
Lentiviral Gene Therapy for Chronic Granulomatous Disease (CGD)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Unknown status
Study Start Date
July 1, 2018 (Actual)
Primary Completion Date
June 30, 2021 (Anticipated)
Study Completion Date
December 31, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shenzhen Geno-Immune Medical Institute
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
This is a Phase I/II clinical trial of gene therapy for treating Chronic Granulomatous Disease using a high-safety, high-efficiency, self-inactivating lentiviral vector TYF to functionally correct the defective gene. The objectives are to evaluate the safety and efficacy of the TYF-CGD gene transfer clinical protocol.
Detailed Description
Chronic granulomatous disease (CGD) is a rare disorder caused by inherited defects in the NADPH oxidase multienzyme complex. It is associated with severe and life-threatening bacterial and fungal infections. Approximately two-thirds of all CGD cases result from mutations within the X-linked gp91phox gene (CYBB), followed by the autosomal recessive forms of CGD, with defects in the gene coding for p47phox (NCF1) accounting for 10-30% of all CGD cases.
The primary objectives are to evaluate the safety of the advanced self-inactivating lentiviral vector TYF-CYBB and TYF-NCF1, the ex-vivo gene transfer clinical protocol and the efficacy of immune reconstitution in patients overcoming frequent infections present at the time of treatment, assessment of vector integration sites, and finally the long-term correction of immune dysfunctions.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Granulomatous Disease
Keywords
Chronic granulomatous disease, Lentiviral vector
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Lentiviral TYF-CGD-modified autologous stem cells
Arm Type
Experimental
Arm Description
Autologous hematopoietic stem cells transduced with lentiviral TYF vector carrying the functional gene
Intervention Type
Genetic
Intervention Name(s)
Infusion of lentiviral TYF-CGD-modified autologous stem cells
Intervention Description
Infusion of lentiviral TYF-modified autologous stem cells at 1~10x10^6 gene-modified cells per kg body weight
Primary Outcome Measure Information:
Title
Overall survival
Description
Patient will be monitored for overall health condition, including immune cell assessments, blood biochemistry and metabolitic activities, metabolic detoxification.
Time Frame
15 year follow up
Title
Gene marking in bone marrow cells
Description
Gene-modified cells in the bone marrow will be measured by vector-specific quantitative PCR of colony-forming cells. Patient overall survival will be followed up for 15 years.
Time Frame
15 year follow up
Secondary Outcome Measure Information:
Title
Change in infection frequency
Time Frame
1 year after treatment by clinical history, complete physical examination, haematological and microbiological tests
Title
Recovery of immune function
Description
Whole blood cell counts (WBC), including CD3+ CD4, CD8 T cells, CD19+ B cells and CD16/CD56 NK cells, and absolute neutrophil counts (ANC), the percentage of NADPH oxidase positive cells, and the kinetics of transduced cells as determined by dihydrorhodamine (DHR) assay, will be measured.
Time Frame
1 year follow up
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
CGD patients >= 0 years of age
Molecular diagnosis confirmed by DNA sequencing and supported by laboratory evidence for absent or significantly reduced biochemical activities of the NADPH-oxidase
Karnofsky-Index > =70%
At least one prior, ongoing or refractory severe infection and/or inflammatory complications requiring hospitalization despite drug intervention
Written informed consent for adult patient, and assent for pediatric subjects seven years or older
Exclusion Criteria:
Contraindication for leukapheresis (anaemia Hb <8g/dl, cardiovascular instability, severe coagulopathy) or for administration of conditioning medication
Female patients who are pregnant or lactating as determined by history and/or positive pregnancy test
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lung-Ji Chang, Ph.D
Phone
86-0755-86725195
Email
c@szgimi.org
Facility Information:
Facility Name
Shenzhen Geno-immune Medical Institute
City
Shenzhen
State/Province
Guangdong
ZIP/Postal Code
China
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lung-Ji Chang, Ph.D
Phone
86-0755-86725195
Email
c@szgimi.org
12. IPD Sharing Statement
Plan to Share IPD
No
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Lentiviral Gene Therapy for CGD
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