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Lentiviral Gene Therapy for CGD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03645486
Recruitment Status : Recruiting
First Posted : August 24, 2018
Last Update Posted : September 19, 2019
Sponsor:
Information provided by (Responsible Party):
Shenzhen Geno-Immune Medical Institute

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.

Condition or disease Intervention/treatment Phase
Chronic Granulomatous Disease Genetic: Infusion of lentiviral TYF-CGD-modified autologous stem cells Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Lentiviral Gene Therapy for Chronic Granulomatous Disease (CGD)
Actual Study Start Date : July 1, 2018
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : December 31, 2021


Arm Intervention/treatment
Experimental: Lentiviral TYF-CGD-modified autologous stem cells
Autologous hematopoietic stem cells transduced with lentiviral TYF vector carrying the functional gene
Genetic: Infusion of lentiviral TYF-CGD-modified autologous stem cells
Infusion of lentiviral TYF-modified autologous stem cells at 1~10x10^6 gene-modified cells per kg body weight




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. Change in infection frequency [ Time Frame: 1 year after treatment by clinical history, complete physical examination, haematological and microbiological tests ]
  2. 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.



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. CGD patients >= 0 years of age
  2. Molecular diagnosis confirmed by DNA sequencing and supported by laboratory evidence for absent or significantly reduced biochemical activities of the NADPH-oxidase
  3. Karnofsky-Index > =70%
  4. At least one prior, ongoing or refractory severe infection and/or inflammatory complications requiring hospitalization despite drug intervention
  5. Written informed consent for adult patient, and assent for pediatric subjects seven years or older

Exclusion Criteria:

  1. Contraindication for leukapheresis (anaemia Hb <8g/dl, cardiovascular instability, severe coagulopathy) or for administration of conditioning medication
  2. Female patients who are pregnant or lactating as determined by history and/or positive pregnancy test

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03645486


Contacts
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Contact: Lung-Ji Chang, Ph.D 86-0755-86725195 c@szgimi.org

Locations
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China, Guangdong
Shenzhen Geno-immune Medical Institute Recruiting
Shenzhen, Guangdong, China, China
Contact: Lung-Ji Chang, Ph.D    86-0755-86725195    c@szgimi.org   
Sponsors and Collaborators
Shenzhen Geno-Immune Medical Institute

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Responsible Party: Shenzhen Geno-Immune Medical Institute
ClinicalTrials.gov Identifier: NCT03645486    
Other Study ID Numbers: GIMI-IRB-18004
First Posted: August 24, 2018    Key Record Dates
Last Update Posted: September 19, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Shenzhen Geno-Immune Medical Institute:
Chronic granulomatous disease
Lentiviral vector
Additional relevant MeSH terms:
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Granuloma
Granulomatous Disease, Chronic
Lymphoproliferative Disorders
Lymphatic Diseases
Pathologic Processes
Phagocyte Bactericidal Dysfunction
Leukocyte Disorders
Hematologic Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Immunologic Deficiency Syndromes
Immune System Diseases