Lentiviral Gene Therapy for CGD

Lentiviral Gene Therapy for Chronic Granulomatous Disease (CGD)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Granulomatous Disease
• Intervention / Treatment: Genetic: Infusion of lentiviral TYF-CGD-modified autologous stem cells

Detailed Description

Important Regulatory Notice:

This trial record is only for global academic information registration on ClinicalTrials.gov. Neither the sponsor Beijing Meikang Jimian Biotechnology Co., Ltd. nor collaborator Shenzhen Geno-Immune Medical Institute has obtained NMPA clinical trial approval or clinical technology filing permission to carry out interventional cell therapy trials in mainland China.

ClinicalTrials.gov registration alone does not represent legal approval by Chinese health and drug regulatory authorities.

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: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lung-Ji Chang, Ph.D; Phone Number: +86 0755-86573763; Email: c@szgimi.org

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Shenzhen Geno-immune Medical Institute
      • Contact: Lung-Ji Chang, Ph.D; Phone Number: +86 0755-86573763; Email: c@szgimi.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

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	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	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	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		1 year after treatment by clinical history, complete physical examination, haematological and microbiological tests
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.	1 year follow up

Collaborators and Investigators

• Sponsor: Shenzhen Geno-Immune Medical Institute

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2027
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: July 24, 2018
• First Submitted That Met QC Criteria: August 22, 2018
• First Posted (Actual): August 24, 2018

Study Record Updates

• Last Update Posted (Actual): August 26, 2026
• Last Update Submitted That Met QC Criteria: August 25, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Lentiviral vector; Chronic granulomatous disease
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Genetic Diseases, Inborn; Immune System Diseases; Leukocyte Disorders; Hematologic Diseases; Immunologic Deficiency Syndromes; Genetic Diseases, X-Linked; Phagocyte Bactericidal Dysfunction; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Granulomatous Disease, Chronic
• Other Study ID Numbers: GIMI-IRB-18004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No