Lentiviral Gene Therapy for CGD

• ClinicalTrials.gov Identifier: NCT03645486
• Recruitment Status: Unknown
• First Posted: August 24, 2018
• Last Update Posted: September 19, 2019
• Sponsor: Shenzhen Geno-Immune Medical Institute
• Information provided by (Responsible Party): Shenzhen Geno-Immune Medical Institute

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.

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Allocation: N/A
• 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

Arms and Interventions

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

Outcome Measures

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.

Eligibility Criteria

• 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

Contacts and Locations

Contacts

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

Locations

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

More Information

• Responsible Party: Shenzhen Geno-Immune Medical Institute
• ClinicalTrials.gov Identifier: NCT03645486
• Other Study ID Numbers: GIMI-IRB-18004
• First Posted: August 24, 2018
• Last Update Posted: September 19, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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:

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; Chronic Disease; Disease Attributes