NCT02234934

Study of Gene Therapy Using a Lentiviral Vector to Treat X-linked Chronic Granulomatous Disease

Completed Phase 1, PHASE2 Last updated 2 May 2025

What this trial tests

Phase 1, PHASE2 trial testing Lentiviral G1XCGD Gene Therapy in Granulomatous Disease, Chronic, X-linked in 10 participants. Completed in 1 December 2024.

Timeline

29 October 2015

Primary endpoint
1 September 2024

1 December 2024

Quick facts

Lead sponsor	University of California, Los Angeles
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	10
Start date	29 October 2015
Primary completion	1 September 2024
Estimated completion	1 December 2024
Sites	3 locations across United States

Drugs / interventions tested

• Lentiviral G1XCGD Gene Therapy — full drug profile →

Conditions studied

• Granulomatous Disease, Chronic, X-linked — all drugs for Granulomatous Disease, Chronic, X-linked →

Sponsor

University of California, Los Angeles

Who can join

23 Months and older, male only, with Granulomatous Disease, Chronic, X-linked. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Chronic Granulomatous Disease (CGD) is an inherited immunodeficiency disorder which results from defects that prevent white blood cells from effectively killing bacteria, fungi and other microorganisms. Chronic granulomatous inflammation may compromise vital organs and account for additional morbidity. CGD is thought to affect approximately 1 in 200,000 persons, although the real incidence might be higher due to under-diagnosis of milder phenotypes.

The first gene therapy approaches in X-CGD have shown that effective gene therapy requires bone-marrow (BM) conditioning with chemotherapy to make space for the gene-modified cells to engraft. These studies demonstrated that transplantation of gene modified stem cells led to production of white blood cells that could clear existing infections. However, some trials using mouse-derived retroviral vectors were complicated by the development of myelodysplasia and leukemia-like growth of blood cells. This trial will evaluate a new lentiviral vector that may be able to correct the defect, but have much lower risk for the complication.

This study is a two-part, prospective non-controlled, non-randomized Phase I/II clinical trial to assess the safety, feasibility and efficacy of cellular gene therapy in patients with chronic granulomatous disease using transplantation of autologous bone marrow CD34+ cells transduced ex vivo by the G1XCGD lentiviral vector containing the human CGD gene. Primary objectives include evaluation of safety and evaluation of efficacy by biochemical and functional reconstitution in progeny of engrafted cells and stability at 12 months. Secondary objectives include evaluation of clinical efficacy, longitudinal evaluation of clinical effect in terms of augmented immunity against bacterial and fungal infection, transduction of CD34+ hematopoietic cells from X-CGD patients by ex vivo lentivirus-mediated gene transfer, and evaluation of engraftment kinetics and stability. Approximately 3-6 patients will be treated per site with a goal of 16 total patients to be treated with G1XCGD lentiviral vector.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Clinical use of lentiviral vectors.
   Milone MC, O'Doherty U. · · 2018 · cited 629× · PMID 29654266 · DOI 10.1038/s41375-018-0106-0
2. Lentiviral gene therapy for X-linked chronic granulomatous disease.
   Kohn DB, Booth C, Kang EM, Pai SY, et al · · 2020 · cited 189× · PMID 31988463 · DOI 10.1038/s41591-019-0735-5
3. A systematic review and meta-analysis of gene therapy with hematopoietic stem and progenitor cells for monogenic disorders.
   Tucci F, Galimberti S, Naldini L, Valsecchi MG, et al · · 2022 · cited 109× · PMID 35288539 · DOI 10.1038/s41467-022-28762-2
4. Update on Clinical Ex Vivo Hematopoietic Stem Cell Gene Therapy for Inherited Monogenic Diseases.
   Tucci F, Scaramuzza S, Aiuti A, Mortellaro A. · · 2021 · cited 72× · PMID 33221437 · DOI 10.1016/j.ymthe.2020.11.020
5. Designing Lentiviral Vectors for Gene Therapy of Genetic Diseases.
   Poletti V, Mavilio F. · · 2021 · cited 64× · PMID 34452394 · DOI 10.3390/v13081526
6. Autologous Stem-Cell-Based Gene Therapy for Inherited Disorders: State of the Art and Perspectives.
   Staal FJT, Aiuti A, Cavazzana M. · · 2019 · cited 61× · PMID 31737588 · DOI 10.3389/fped.2019.00443
7. Clinical applications of gene therapy for primary immunodeficiencies.
   Cicalese MP, Aiuti A. · · 2015 · cited 53× · PMID 25860576 · DOI 10.1089/hum.2015.047
8. Immunological barriers to haematopoietic stem cell gene therapy.
   Charlesworth CT, Hsu I, Wilkinson AC, Nakauchi H. · · 2022 · cited 47× · PMID 35301483 · DOI 10.1038/s41577-022-00698-0