SCID-X1 Gene Therapy Via Intravenous Lentiviral (Ivlv-X1) Injection

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

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.

Study Overview

• Status: Recruiting
• Conditions: SCID, X-Linked
• Intervention / Treatment: Biological: Direct intravenous injection of ivlv-X1 lentiviral vector

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Lung-Ji Chang, Ph.D; Phone Number: 86-075586725195; Email: c@szgimi.org

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Geno-immune Medical Institute
      • Contact: Lung-Ji Chang, PhD; Phone Number: 86-075586725195; Email: c@szgimi.org
  • Guangxi
    • Guilin, Guangxi, China
      • Recruiting
      • Guilin Hospital of Chinese Traditional and Western Medicine
      • Contact: Qiyong Zhu, MD; Phone Number: +86-13683284467; Email: 1250109112@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 10 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm; In vivo LV gene transfer to treat SCID-X1	Biological: Direct intravenous injection of ivlv-X1 lentiviral vector; ivlv-X1 LV intravenous injection at a dose of ~1x10e9/kg body weight.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		1 year
Overall immune reconstitution	T and B cell recovery	1 year
Change of infection status		1 year

Collaborators and Investigators

• Sponsor: Shenzhen Geno-Immune Medical Institute
• Investigators: Principal Investigator: Lung-Ji Chang, Ph.D, Shenzhen Geno-immune Medical Institute; Study Director: Qiyong Zhu, MD, Guilin Hospital of Chinese Traditional and Western Medicine

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: July 3, 2017
• First Submitted That Met QC Criteria: July 11, 2017
• First Posted (Actual): July 14, 2017

Study Record Updates

• Last Update Posted (Estimated): September 9, 2025
• Last Update Submitted That Met QC Criteria: September 8, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: lentiviral vector; SCID-X1; intravenous gene transfer
• Additional Relevant MeSH Terms: Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Immune System Diseases; Infant, Newborn, Diseases; Immunologic Deficiency Syndromes; Genetic Diseases, X-Linked; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Severe Combined Immunodeficiency; X-Linked Combined Immunodeficiency Diseases
• Other Study ID Numbers: GIMI-IRB-17014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No