SCID, X-Linked
Conditions
Keywords
SCID-X1, lentiviral vector, intravenous gene transfer
Brief summary
This is a Phase I/II gene therapy trial treating X-linked severe combined immunodeficiency (SCID-X1) using a self-inactivating lentiviral vector (ivlv-X1) to functionally correct the genetic defect. The primary objectives are to evaluate the safety and efficacy of the direct intravenous lentiviral gene transfer 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. X-linked severe combined immunodeficiency (SCID-X1) is a genetic disorder caused by defect in the common cytokine receptor chain, normally on the surface of lymphocytes. Individuals with SCID-X1 lack the normal development of a functional immune system and so have difficulty fighting infections, which may lead to chronic or severe illness and death. X-SCID patients are normally rescued by a bone marrow transplant from a healthy donor. This trial aims to treat SCID-X1 using a self-inactivating lentiviral vector (LV) carrying a functional gene to correct the genetic defect. By direct intravenous (iv) injection of the LV (ivlv-X1) to modify immune cells in the body, this treatment may establish normal healthy immune cells and overcome the immunodeficiency. The primary objectives are to evaluate the safety of the self-inactivating ivlv-X1-LV, the in vivo gene transfer protocol and the efficacy of immune reconstitution in patients overcoming frequent infections present at the time of treatment, assessment of iv LV gene transfer efficiency, and finally the long-term correction of immunodeficiency.
Interventions
BIOLOGICALDirect intravenous injection of ivlv-X1 lentiviral vector
ivlv-X1 LV intravenous injection at a dose of \~1x10e9/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
MALE
Age
1 Months to 1 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of SCID-X1 based on: * A proven mutation in the common interleukin-2 receptor gamma chain 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 antigen stimulation. 2. No available HLA identical related donor. 3. With severe infections, including but not limited to: pneumonitis; protracted diarrhea requiring total parenteral nutrition; infection with herpes viruses or adenovirus; disseminated BCG infection. 4. No cytogenetic abnormalities (medullary karyotype) and no detection of main rearrangements associated with acute leukemia. 5. No prior allogeneic stem cell transplantation. 6. Life expectancy ≥ 3 months. 7. Documented to be negative for HIV infection. 8. Written, informed consent obtained prior to any study-specific procedures.
Exclusion criteria
1. No available molecular diagnosis confirming SCID-X1. 2. Existence of an available HLA-identical related donor. 3. Diagnosis of active malignant disease other than EBV-associated lymphoproliferative disease. 4. Current treatment with any chemotherapeutic agent (becomes eligible if not on treatment for at least 1 month). 5. Patients with evidence of infection with HIV-1 or 2. 6. Presence of a medical condition indicating that survival will be less than 4 weeks such as the requirement for mechanical ventilation, severe failure of a major organ system, or evidence of a serious, progressive infection that is refractory to medical treatment. 7. Current treatment with any immunosuppressive agent, excluding corticosteroids. 8. Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 1 year | — |
| Overall immune reconstitution | 1 year | T and B cell recovery |
| Change of infection status | 1 year | — |
Countries
China
Contacts
CONTACTLung-Ji Chang, Ph.D
PRINCIPAL_INVESTIGATORLung-Ji Chang, Ph.D
Shenzhen Geno-Immune Medical Institute
Outcome results
None listed