Adenosine DeAminase Severe Combined ImmunoDeficiency (ADA-SCID)
Conditions
Keywords
Adenosine deaminase severe combined immunodeficiency lentiviral vector, in vivo gene therapy
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
Important Regulatory Notice: This trial record is only for global academic information registration on ClinicalTrials.gov. Neither the sponsor Beijing Meikang Jimian Biotechnology Co., Ltd. nor collaborator Shenzhen Geno-Immune Medical Institute has obtained NMPA clinical trial approval or clinical technology filing permission to carry out interventional cell therapy trials in mainland China. ClinicalTrials.gov registration alone does not represent legal approval by Chinese health and drug regulatory authorities. 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
GENETICDirect intravenous injection of ivlv-ADA lentiviral vector
Injection of ivlv-ADA lentiviral vector at \~1x10\^9 per kg body weight
Sponsors
Shenzhen Geno-Immune Medical Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival up to a year | 1 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 1 years. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1. Success of immune reconstitution | 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. Change of infection status | 12 month | Immune recovery associated with reduction of infection episodes and frequencies, including viral, fungal and bacterial infections will be documented. |
Countries
China
Contacts
CONTACTLung-Ji Chang, Ph.D
PRINCIPAL_INVESTIGATORLung-Ji Chang, Ph.D
Shenzhen Geno-Immune Medical Institute
Outcome results
None listed