A Gene Therapy Trial to Evaluate the Safety and Efficacy of the Infusion of Autologous Hematopoietic Stem Cells Transduced With RP-L201
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|ClinicalTrials.gov Identifier: NCT03825783|
Recruitment Status : Active, not recruiting
First Posted : January 31, 2019
Last Update Posted : January 31, 2019
|Condition or disease||Intervention/treatment||Phase|
|Leukocyte Adhesion Defect - Type I||Biological: RP-L201||Phase 1|
The study is a pediatric non-randomized open-label Phase I clinical trial. This will include a safety evaluation and preliminary assessment of the efficacy of hematopoietic gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the ITGB2 gene in subjects with severe Leukocyte Adhesion Deficiency-I (LAD-I). Subjects will undergo mobilization and collection of peripheral blood hematopoietic stem cells (HSCs) with granulocyte-colony stimulating factor (G-CSF) and plerixafor or bone marrow harvest in select circumstances.
HSCs will then be transduced with the therapeutic vector (Chim.hCD18-LV), with the intent of enabling stable integration of the provirus in the genome of stem and progenitor cells.
If the number of CD34+ cells that are cryopreserved is at least 4×10E6 total CD34+ cells/kg, subjects will receive myeloablative conditioning with intravenous busulfan. The gene-modified CD34+ cells will be then transplanted back into the subject.
Once engrafted, it is anticipated that the gene-modified stem and progenitor cells will enable hematopoiesis, generating blood cells in which the integrated therapeutic gene (ITGB2) will be transcribed and translated to produce the therapeutic CD18 protein with a preferential high expression in mature myeloid cells. Leukocytes expressing a functional CD18 will have the capability to arrest on endothelial surfaces and extravasate to infectious sites, enabling a competent antimicrobial response and reversing the clinical disorder.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||2 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Gene Therapy for Leukocyte Adhesion Deficiency-I (LAD-I): A Phase I Clinical Trial to Evaluate the Safety and Efficacy of the Infusion of Autologous Hematopoietic Stem Cells Transduced With a Lentiviral Vector Encoding the ITGB2 Gene.|
|Actual Study Start Date :||January 28, 2019|
|Estimated Primary Completion Date :||July 2021|
|Estimated Study Completion Date :||July 2021|
RP-L201 is a gene therapy product containing autologous genetically modified CD34+ hematopoietic stem cells transduced with Chim-CD18-WPRE lentiviral vector administered as a single infusion in subjects with severe LAD-I
CD34+ enriched hematopoietic stem cells from subjects with severe LAD-I transduced ex vivo with lentiviral vector carrying the ITGB2 gene, Chim-CD18-WPRE.
- Number of participants with treatment-related adverse events as assessed by United States (US) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 [ Time Frame: 2 years ]Evaluation of safety associated with treatment with RP-L201
- Survival following infusion of RP-L201 [ Time Frame: 2 years ]Evaluation of survival as determined by the proportion of subjects alive at age 2 (24 months) and at least 1-year post infusion without allogeneic hematopoietic stem cell transplant
- CD18 expression after infusion of RP-L201 [ Time Frame: 2 years ]Determination of the percentage of subjects in whom infusion of RP-L201 results in a change in the percentage of neutrophils expressing CD18 to at least 10% in 2 years
- Genetic correction after infusion of RP-L201 [ Time Frame: 6 months ]Determination of whether infusion of RP-L201 results in vector copy number/cell of at least 0.1 in peripheral blood neutrophils carrying the therapeutic Chim.hCD18-LV provirus at 6 months post-infusion
- Incidence of infections after infusion of RP-L201 [ Time Frame: 2 years ]Determination of the incidence and severity of bacterial or other infections (subsequent to hematopoietic reconstitution)
- Assessment of number of participants with a change in LAD-I-associated neutrophilia after infusion of RP-L201 [ Time Frame: 2 years ]Evaluation of change to partially normal or to normal levels of LAD-I-associated neutrophilia
- Assessment of number of participants with a change in skin lesions or periodontal abnormalities after infusion of RP-L201 [ Time Frame: 2 years ]Evaluation of resolution (partial or complete) of any underlying skin lesions or periodontal abnormalities
- Assessment of overall survival after infusion of RP-L201 [ Time Frame: 2 years ]Evaluation of overall survival (beyond age 2 years and beyond the initial year subsequent to investigational therapy)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03825783
|Hospital Infantil Universitario Niño Jesús (HIUNJ)|
|Madrid, Spain, 28009|
|Principal Investigator:||Julián Sevilla Navarro, MD, PhD||Hospital Infantil Universitario Niño Jesús (HIUNJ)|