- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03645486
Lentiviral Gene Therapy for CGD
Lentiviral Gene Therapy for Chronic Granulomatous Disease (CGD)
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Lung-Ji Chang, Ph.D
- Phone Number: 86-0755-86725195
- Email: c@szgimi.org
Study Locations
-
-
Guangdong
-
Shenzhen, Guangdong, China, China
- Recruiting
- Shenzhen Geno-Immune Medical Institute
-
Contact:
- Lung-Ji Chang, Ph.D
- Phone Number: 86-0755-86725195
- Email: c@szgimi.org
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Lentiviral TYF-CGD-modified autologous stem cells
Autologous hematopoietic stem cells transduced with lentiviral TYF vector carrying the functional gene
|
Infusion of lentiviral TYF-modified autologous stem cells at 1~10x10^6 gene-modified cells per kg body weight
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival
Time Frame: 15 year follow up
|
Patient will be monitored for overall health condition, including immune cell assessments, blood biochemistry and metabolitic activities, metabolic detoxification.
|
15 year follow up
|
Gene marking in bone marrow cells
Time Frame: 15 year follow up
|
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.
|
15 year follow up
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in infection frequency
Time Frame: 1 year after treatment by clinical history, complete physical examination, haematological and microbiological tests
|
1 year after treatment by clinical history, complete physical examination, haematological and microbiological tests
|
|
Recovery of immune function
Time Frame: 1 year follow up
|
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.
|
1 year follow up
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- GIMI-IRB-18004
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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