Gene Therapy for ADA-SCID Using an Improved Lentiviral Vector (Ivlv-ADA)

Last updated: July 15, 2024
Sponsor: Shenzhen Geno-Immune Medical Institute
Overall Status: Active - Recruiting

Phase

N/A

Condition

Hiv Infections

Treatment

Direct intravenous injection of ivlv-ADA lentiviral vector

Clinical Study ID

NCT03645460
GIMI-IRB-18003
  • Ages > 1
  • All Genders

Study Summary

This is a Phase I/II trial of in vivo lentiviral gene therapy for treating adenosine deaminase severe combined immunodeficiency (ADA-SCID) using a self-inactivating lentiviral vector (LV) ivlv-ADA to functionally correct the genetic defect. The primary objectives are to evaluate the safety and efficacy of the direct intravenous (iv) LV gene therapy protocol.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Diagnosis of classical ADA-SCID based on:

  • A proven defective adenosine deaminase (ADA) gene as defined by directsequencing 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 vitromitogen stimulation, or absent proliferation in vitro to antigens.

  • With severe infections, including but not limited to: pneumonitis; protracteddiarrhea requiring total parenteral nutrition; infection with herpes viruses oradenovirus or fungus; disseminated BCG infection.

  • No cytogenetic abnormalities (medullary karyotype) and no detection of mainrearrangements 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

Exclusion Criteria:

  • None

Study Design

Total Participants: 10
Treatment Group(s): 1
Primary Treatment: Direct intravenous injection of ivlv-ADA lentiviral vector
Phase:
Study Start date:
June 30, 2024
Estimated Completion Date:
December 31, 2027

Study Description

This clinical trial will evaluate safety and efficiency of an improved LV 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 via direct intravenous (iv) injection of a safety and efficiency improved self-inactivating LV carrying a functional ADA gene (ivlv-ADA) to correct the genetic defect. By direct iv injection of ivlv-ADA, the defective immune cells and blood stem cells in the body can be modified to exhibit ADA activity and correct the immunodeficiency.

The primary objectives are to evaluate the safety of the improved ivlv-ADA, the iv LV gene transfer clinical protocol and the efficacy of immune recovery in patients to overcome frequent infections present at the time of treatment. We will assess the in vivo lentiviral gene transfer efficiency and the long-term effect of this gene transfer procedure.

Connect with a study center

  • Shenzhen Geno-immune Medical Institute

    Shenzhen, Guangdong 518000
    China

    Active - Recruiting

  • Guilin Hospital of Chinese Traditional and Western Medicine

    Guilin, Guangxi
    China

    Active - Recruiting

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