Ignite Creation Date:
2024-05-06 @ 3:54 PM
Last Modification Date:
2025-12-16 @ 8:18 PM
Study NCT ID:
NCT04797260
Status:
None
Last Update Posted:
2024-04-18 00:00:00
First Post:
2021-03-11 00:00:00
Brief Title:
Phase I/II Clinical Trial Stem Cell Gene Therapy in RAG1-Deficient SCID
Sponsor:
Leiden University Medical Center
Organization:
Leiden University Medical Center
Study Overview
Official Title:
Phase I/II Clinical Trial of Autologous Hematopoietic Stem Cell Gene Therapy in RAG1-Deficient Severe Combined Immunodeficiency
Status:
None
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
RAG1-SCID
Brief Summary:
Severe combined immunodeficiency (SCID) is a genetically heterogeneous life-threatening disease characterized by severely impaired T cell development with or without impaired natural killer (NK) and B cell development or function depending on the genetic defect. Mutations in recombination activating genes 1 and 2 (RAG1 and RAG2) represent about 20% of all types of SCID. SCID is a paediatric emergency since it leads to severe and recurrent infections often in combination with protracted diarrhoea and failure to thrive. When left untreated, it is usually fatal within the first year of life. Currently, the only curative treatment option for RAG-deficient SCID is allogeneic hematopoietic stem cell transplantation (HSCT). Despite improvements in HSCT in recent years, this treatment is associated with serious potential complications like graft-versus-host disease which results in an unfavourable outcome, particularly in patients who lack a human leukocyte antigen (HLA)-matched donor. In recent years, gene therapy based on transplantation of autologous gene-corrected hematopoietic stem cells (HSC) has evolved as an effective and safe therapeutic option for X-linked and ADA-deficient forms of SCID. We have recently demonstrated that gene therapy using lentiviral (LV) self-inactivating (SIN) vectors expressing codon-optimized human RAG1 in a mouse model for RAG1-deficient SCID effectively restores T and B cell development and function. In this phase I/II explorative intervention study feasibility, safety and efficacy of gene therapy using gene-corrected autologous CD34+-selected mobilized peripheral blood or bone marrow cells will be investigated in patients with RAG1-deficient SCID with an indication for allogeneic HSCT but lacking an human leukocyte antigen (HLA)-matched donor.
Detailed Description:
Severe combined immunodeficiency SCID is a genetically heterogeneous life-threatening disease characterized by severely impaired T cell development with or without impaired natural killer NK and B cell development or function depending on the genetic defect Mutations in recombination activating genes 1 and 2 RAG1 and RAG2 represent about 20 of all types of SCID SCID is a paediatric emergency since it leads to severe and recurrent infections often in combination with protracted diarrhoea and failure to thrive When left untreated it is usually fatal within the first year of life Currently the only curative treatment option for RAG-deficient SCID is allogeneic hematopoietic stem cell transplantation HSCT Despite improvements in HSCT in recent years this treatment is associated with serious potential complications like graft-versus-host disease which results in an unfavourable outcome particularly in patients who lack a human leukocyte antigen HLA-matched donor In recent years gene therapy based on transplantation of autologous gene-corrected hematopoietic stem cells HSC has evolved as an effective and safe therapeutic option for X-linked and ADA-deficient forms of SCID We have recently demonstrated that gene therapy using lentiviral LV self-inactivating SIN vectors expressing codon-optimized human RAG1 in a mouse model for RAG1-deficient SCID effectively restores T and B cell development and function In this phase III explorative intervention study feasibility safety and efficacy of gene therapy using gene-corrected autologous CD34-selected mobilized peripheral blood or bone marrow cells will be investigated in patients with RAG1-deficient SCID with an indication for allogeneic HSCT but lacking an human leukocyte antigen HLA-matched donor
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None