A Clinical Trial to Evaluate the Safety of RP-L102 in Pediatric Subjects With Fanconi Anemia Subtype A
|ClinicalTrials.gov Identifier: NCT03814408|
Recruitment Status : Active, not recruiting
First Posted : January 24, 2019
Last Update Posted : June 25, 2019
|Condition or disease||Intervention/treatment||Phase|
|Fanconi Anemia Complementation Group A||Biological: RP-L102||Phase 1|
This is a pediatric open-label Phase 1 clinical trial and 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 FANCA gene in subjects with FA-A. CD34+ cells will be transduced ex vivo with the therapeutic lentiviral vector and infused following transduction, without any prior conditioning. After transduction, product quality control evaluations will be carried out in aliquots of the transduced population. Investigational product will be infused via intravenous infusion with no upper or lower limit; a dose of ≥5 x 105 CD34+ cells/kg body weight will be considered optimal.
The active agent is a self-inactivating lentiviral vector carrying the therapeutic FANCA gene and the therapeutic product is subject's autologous HSCs that have been transduced with the lentiviral vector. The vector contains the functional FANCA gene.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||2 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Clinical Trial to Evaluate the Safety of the Infusion of Autologous CD34+ Cells Transduced With a Lentiviral Vector Carrying the FANCA Gene in Pediatric Subjects With Fanconi Anemia Subtype A|
|Actual Study Start Date :||January 11, 2019|
|Estimated Primary Completion Date :||September 2019|
|Estimated Study Completion Date :||March 2022|
RP-L102 is a self-inactivating lentiviral vector carrying the therapeutic FANCA gene
CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with lentiviral vector carrying the FANCA gene, PGK-FANCA-WPRE
- Number of participants with treatment-related adverse events as assessed by CTCAE v.5.0 [ Time Frame: 3 years ]Evaluation of safety associated with treatment with RP-L102
- Phenotypic correction of T-lymphocytes in peripheral blood after infusion of RP-L102 [ Time Frame: 3 years ]Assessment of the percentage of peripheral blood T-cells with DEB-induced chromosomal aberrations that decreases from over or equal to 50% at 0-2 months post-infusion to less than 50% during months 6-36 post-infusion (confirmed in at least 2 determinations conducted in each interval).
- Phenotypic correction of hematopoietic cells in bone marrow after infusion of RP-L102 [ Time Frame: 3 years ]During months 6-36 post-infusion, the survival of bone marrow colony forming units to 10nM MMC increases to over or equal to 10% than values determined at 0-2 months post-infusion. (1 determination is considered valid).
- Engraftment of gene-corrected hematopoietic cells after infusion of RP-L102 [ Time Frame: 3 years ]The level of gene marking of the FANCA-LV provirus in total peripheral blood cells is at least 0.1 vector copy number/nucleated cell during months 6-36 post-infusion. (This should be confirmed in at least 2 determinations conducted at different intervals). An increase in the vector copy number/peripheral blood cell is observed from 0-2 months post-infusion to the 3rd year post-infusion. (This should be confirmed in at least 2 determinations conducted in each interval periods).
- Prevention or rescue of bone marrow failure after infusion of RP-L102 [ Time Frame: 3 years ]Assessment of the need for treatment of bone marrow failure 6-36 months post-infusion. During the 3rd year post-infusion, peripheral blood parameters: hemoglobin levels, neutrophils, and platelets will be assessed and considered stable if they remain at over or equal to 80% of values determined at pre-treatment evaluation visit or immediately prior to mobilization before the administration of granulocyte-colony stimulating factor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03814408
|United States, California|
|Stanford University Institute for Stem Cell Biology and Regenerative Medicine Lucille Packard Children's Hospital, Stanford University|
|Stanford, California, United States, 94304|
|Principal Investigator:||Sandeep Soni, MD||Stanford University, Stem Cell Transplantation and Regenerative Medicine|