Grant Award Details
To conduct a Phase 1/2 non-randomized, multicenter, open-label study of G1XCGD (lentiviral vector transduced autologous CD34+ cells in patients with X-linked chronic granulomatous disease. A total of 10 subjects are planned to be enrolled . There are 3 clinical sites involved in this study - UCLA, Boston Children and NIH clinical center.
Grant Application Details
- A Phase I/II, Non Randomized, Multicenter, Open-Label Study of G1XCGD (Lentiviral Vector Transduced CD34+ Cells) in Patients With X-Linked Chronic Granulomatous Disease
Therapeutic Candidate or Device
The therapeutic product candidate is autologous CD34+ hematopoietic stem/progenitor cells (HSPC) transduced with the G1XCGD lentiviral vector.
The target indication is for the transplantation of patients with severe X-linked Chronic Granulomatous Disease (XCGD) lacking matched donors.
Transplantation and engraftment of gene-corrected autologous HSPC after reduced intensity conditioning for XCGD may lead to sustained production of white blood cells that have the capacity to kill infectious microorganisms and eliminate or prevent severe recurrent infections. Autologous transplants may be as effective and safer than transplants from an unrelated donor to alleviate disease manifestations.
Unmet Medical Need
Hematopoietic stem cell transplantation (HSCT) from non-fully matched donors may have immune complications and requires potent immune suppression. Effective autologous HSCT with G1XCGD lentiviral vector-mediated gene correction could have similar benefits but be safer with less complications.
The objective is to complete a Phase I/II trial.
Major Proposed Activities
- Perform two year follow up to assess trial end-points to assess safety and efficacy.
- Transplant 10 subjects with severe XCGD lacking matched donors with the autologous stem cell product after reduced intensity conditioning.
- Perform GMP manufacture of 10 patient-specific lots of G1XCGD transduced autologous CD34+ HSPC meeting release criteria.
Patients with primary immune deficiency diseases, such as XCGD, have severe and recurrent infections, necessitating extensive medical therapy and leading to significant morbidity and early mortality. Transplantation of their own hematopoietic stem cells corrected with the normal gene may provide cures for XCGD as well as other inherited blood cell disorders (SCID or "bubble baby disease", sickle cell disease, Lorenzo’s Oil disease), and potentially provide novel curative approaches to HIV/AIDS.