Gene therapy for X-linked severe combined immunodeficiency

Gene Therapy for X-linked Severe Combined Immunodeficiency (SCID-X1) Via Direct Intravenous Injection of Lentiviral Vector (Ivlv-X1)

This study is testing a new gene therapy for children with X-linked severe combined immunodeficiency to see if it can help their immune system fight off infections better.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 1 Month to 1 Year
• Sex: Male
• Sponsor: Shenzhen Geno-Immune Medical Institute (other)
• Locations: 2 sites (Shenzhen, Guangdong and 1 other locations)
• Trial ID: NCT03217617 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to treat X-linked severe combined immunodeficiency (SCID-X1) using a self-inactivating lentiviral vector delivered through direct intravenous injection. The study focuses on evaluating the safety and efficacy of this gene therapy approach, which seeks to correct the genetic defect responsible for the disorder. Participants will be monitored for immune reconstitution and the ability to overcome frequent infections. The trial includes both Phase I and Phase II assessments to ensure comprehensive evaluation of the treatment's impact.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals diagnosed with SCID-X1 who lack an available HLA identical related donor and are experiencing severe infections.

Not a fit: Patients with cytogenetic abnormalities or those who have previously undergone allogeneic stem cell transplantation may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a functional immune system for patients with SCID-X1, significantly improving their quality of life and survival rates.

How similar studies have performed: Other studies using gene therapy for similar genetic disorders have shown promising results, indicating potential for success in this approach.

Eligibility criteria

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.

Where this trial is running

Shenzhen, Guangdong and 1 other locations

• Shenzhen Geno-immune Medical Institute — Shenzhen, Guangdong, China (RECRUITING)
• Guilin Hospital of Chinese Traditional and Western Medicine — Guilin, Guangxi, China (RECRUITING)

Study contacts

• Principal investigator: Lung-Ji Chang, Ph.D — Shenzhen Geno-Immune Medical Institute
• Study coordinator: Lung-Ji Chang, Ph.D

Conditions: SCID, X-Linked, SCID-X1, lentiviral vector, intravenous gene transfer