Clinical trial NCT03645460: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Adenosine DeAminase Severe Combined ImmunoDeficiency (ADA-SCID)
Keywords: Adenosine deaminase severe combined immunodeficiency lentiviral vector
in vivo gene therapy
Lead sponsor: Shenzhen Geno-Immune Medical Institute
Sponsor class: OTHER
First posted: 2018-08-24
Enrollment: 10
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

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

Primary outcomes:
measure: Overall survival up to a year
timeFrame: 1 years
Secondary outcomes:
measure: 1. Success of immune reconstitution
timeFrame: 12 month
measure: 2. Change of infection status
timeFrame: 12 month
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Shenzhen Geno-immune Medical Institute
state: Guangdong
city: Guilin
country: China
facility: Guilin Hospital of Chinese Traditional and Western Medicine
state: Guangxi
Study officials:
affiliation: Shenzhen Geno-Immune Medical Institute
name: Lung-Ji Chang, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: