Lentiviral Gene Therapy for CGD

September 18, 2019 updated by: Shenzhen Geno-Immune Medical Institute

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

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

Enrollment (Anticipated)

10

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Lung-Ji Chang, Ph.D
  • Phone Number: 86-0755-86725195
  • Email: c@szgimi.org

Study Locations

    • Guangdong
      • Shenzhen, Guangdong, China, China
        • Recruiting
        • Shenzhen Geno-Immune Medical Institute
        • Contact:
          • Lung-Ji Chang, Ph.D
          • Phone Number: 86-0755-86725195
          • Email: c@szgimi.org

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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
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
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.
15 year follow up
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.
15 year follow up

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in infection frequency
Time Frame: 1 year after treatment by clinical history, complete physical examination, haematological and microbiological tests
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.
1 year follow up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2018

Primary Completion (Anticipated)

June 30, 2021

Study Completion (Anticipated)

December 31, 2021

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)

September 19, 2019

Last Update Submitted That Met QC Criteria

September 18, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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