Lentiviral Gene Therapy for CGD

Chronic Granulomatous Disease Clinical Trial

Official title:

Lentiviral Gene Therapy for Chronic Granulomatous Disease (CGD)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03645486
• Other study ID #: GIMI-IRB-18004
• Status: Recruiting
• Phase: N/A
• Start date: July 1, 2018
• Est. completion date: December 31, 2021

Study information

• Verified date: September 2019
• Source: Shenzhen Geno-Immune Medical Institute
• Contact: Lung-Ji Chang, Ph.D
• Phone: 86-0755-86725195
• Email: c[@]szgimi.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: December 31, 2021
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Granulomatous Disease
• Granuloma
• Granulomatous Disease, Chronic

Intervention

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

Locations

Country	Name	City	State
China	Shenzhen Geno-immune Medical Institute	Shenzhen	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Shenzhen Geno-Immune Medical Institute

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Change in infection frequency		1 year after treatment by clinical history, complete physical examination, haematological and microbiological tests
Secondary	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