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

Official title

Gene Therapy Via Intravenous Injection of Lentiviral Vector (Ivlv-ADA) for the Treatment of Adenosine Deaminase-severe Combined Immunodeficiency (ADA-SCID)

Overview

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.

Detailed 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.

Interventions

• Genetic Direct intravenous injection of ivlv-ADA lentiviral vector
  Injection of ivlv-ADA lentiviral vector at \~1x10\^9 per kg body weight

Primary outcome measures

• Overall survival up to a year [Time frame: 1 years]

Secondary outcome measures (2)

• 1. Success of immune reconstitution [Time frame: 12 month]
• 2. Change of infection status [Time frame: 12 month]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shenzhen Geno-immune Medical Institute — Shenzhen

Identifiers

NCT: NCT03645460 · GIMI-IRB-18003

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗