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Gene Transfer for ADA-SCID Using an Improved Lentiviral Vector (TYF-ADA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03645460
Recruitment Status : Unknown
Verified September 2019 by Shenzhen Geno-Immune Medical Institute.
Recruitment status was:  Recruiting
First Posted : August 24, 2018
Last Update Posted : September 20, 2019
Information provided by (Responsible Party):
Shenzhen Geno-Immune Medical Institute

Brief Summary:
Gene transfer for ADA-SCID using an improved lentiviral vector (TYF-ADA)

Condition or disease Intervention/treatment Phase
Adenosine DeAminase Severe Combined ImmunoDeficiency (ADA-SCID) Genetic: TYF-ADA gene-modified autologous stem cells Not Applicable

Detailed Description:

This clinical trial will evaluate a safety and efficiency improved lentiviral vector system for delivering a therapeutic gene to patients with severe combined immunodeficiency (SCID) due to a defective adenosine deaminase (ADA) gene. This gene encodes for the adenosine deaminase enzyme, which is essential for the proper growth and function of infection-fighting white blood cells called T and B lymphocytes. Patients who lack this enzyme are vulnerable to frequent and severe infections.

ADA-SCID patients are normally rescued by a bone marrow transplant (BMT) from a matched healthy donor. However, matched donors are difficult to find and donor BMT is associated with high risk. This trial aims to treat ADA-SCID using a safety and efficiency improved self-inactivating lentiviral vector carrying a functional ADA gene to correct the genetic defect. By collecting an individual's stem cells and modifying them with a lentivirus, the gene-corrected cells can be returned to the patient to help produce normal healthy immune cells.The primary objectives are to evaluate the safety of the improved self-inactivating lentiviral vector TYF-ADA, the ex vivo gene transfer clinical protocol and the efficacy of immune reconstitution in patients overcoming frequent infections present at the time of treatment. We will assess the lentiviral gene integration sites and the long-term effect of this gene transfer procedure.

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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: Gene Transfer for Adenosine Deaminase-severe Combined Immunodeficiency (ADA-SCID) Using an Improved Self-inactivating Lentiviral Vector (TYF-ADA)
Actual Study Start Date : October 30, 2018
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2021

Arm Intervention/treatment
Experimental: TYF-ADA-modified autologous stem cells
Autologous hematopoietic and/or mesenchymal stem cells transduced with lentiviral vector carrying the ADA gene
Genetic: TYF-ADA gene-modified autologous stem cells
Infusion of TYF-ADA-modified autologous stem cells at 1~10x10^6 gene-modified cells per kg body weight; or more infusions depending on the circumstances

Primary Outcome Measures :
  1. Overall survival up to a year [ Time Frame: 15 years ]
    Patient will be monitored for overall health condition, including immune cell assessments, blood biochemistry and metabolitic activities, metabolic detoxification, gene-modified cell percentage and vector copy number (VCN) in the blood, and continued follow-up for 15 years.

Secondary Outcome Measures :
  1. 1. Success of immune reconstitution [ Time Frame: 12 month ]
    Immunological and metabolic values including all leukocyte counts (ALC), T, B and NK cell counts (CD3, CD4, CD8, CD19, CD56), T cell TREC levels, T cell repertoire diversity, PHA proliferation rate, immunoglobulins and dATP levels will be measured.

  2. 2. Change of infection status [ Time Frame: 12 month ]
    Immune recovery associated with reduction of infection episodes and frequencies, including viral, fungal and bacterial infections will be documented.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   1 Month and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of classical ADA-SCID based on:

    • A proven defective adenosine deaminase (ADA) gene as defined by direct sequencing of patient DNA.
    • T-cell immune deficiency defined as one or more of the following: CD3+ autologous T cells < 300/ul, or less than 50% of normal value for in vitro mitogen stimulation, or absent proliferation in vitro to antigens.
  • With severe infections, including but not limited to: pneumonitis; protracted diarrhea requiring total parenteral nutrition; infection with herpes viruses or adenovirus or fungus; disseminated BCG infection.
  • No cytogenetic abnormalities (medullary karyotype) and no detection of main rearrangements associated with acute leukemia of children.
  • No prior allogeneic stem cell transplantation.
  • Life expectancy ≥ 2 months.
  • Negative for HIV infection.
  • Written, informed consent obtained prior to any study-specific procedures.

Exclusion Criteria:

  • None

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03645460

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Contact: Lung-Ji Chang, Ph.D 86-0755-86725195

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China, Guangdong
Shenzhen Geno-immune Medical Institute Recruiting
Shenzhen, Guangdong, China, 518000
Contact: Lung-Ji Chang, Ph.D    86-0755-86725195   
Principal Investigator: XiaoDong Shi, M.D./P.H.D         
Principal Investigator: Jie Zheng, M.D./P.H.D         
Sponsors and Collaborators
Shenzhen Geno-Immune Medical Institute
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Principal Investigator: Lung-Ji Chang, Ph.D Shenzhen Geno-Immune Medical Institute
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Responsible Party: Shenzhen Geno-Immune Medical Institute Identifier: NCT03645460    
Other Study ID Numbers: GIMI-IRB-18003
First Posted: August 24, 2018    Key Record Dates
Last Update Posted: September 20, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
Adenosine deaminase severe combined immunodeficiency lentiviral vector
Additional relevant MeSH terms:
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Severe Combined Immunodeficiency
Immunologic Deficiency Syndromes
Immune System Diseases
Primary Immunodeficiency Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases