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

Tracking Information

• First Submitted Date: July 24, 2018
• First Posted Date: August 24, 2018
• Last Update Posted Date: September 19, 2019
• Actual Study Start Date: July 1, 2018
• Estimated Primary Completion Date: June 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 22, 2018)

• 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.
• 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 22, 2018)

• Change in infection frequency [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Lentiviral Gene Therapy for CGD
• Official Title: Lentiviral Gene Therapy for Chronic Granulomatous Disease (CGD)
• 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.

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: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Chronic Granulomatous Disease

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

Study Arms

Experimental: Lentiviral TYF-CGD-modified autologous stem cells

Autologous hematopoietic stem cells transduced with lentiviral TYF vector carrying the functional gene

Intervention: Genetic: Infusion of lentiviral TYF-CGD-modified autologous stem cells

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: August 22, 2018): 10
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2021
• Estimated Primary Completion Date: June 30, 2021 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03645486
• Other Study ID Numbers: GIMI-IRB-18004
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Shenzhen Geno-Immune Medical Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Shenzhen Geno-Immune Medical Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Shenzhen Geno-Immune Medical Institute
• Verification Date: September 2019