Table 3.
Gene Editing and Gene Therapies for Sickle Cell Disease.
| Title | ClinicalTrials.gov | Status | Mechanism | Notes |
|---|---|---|---|---|
| Gene therapies using lentiviral globin addition | ||||
| Safety and efficacy of LentiGlobin BB305 in β-thalassemia and SCD | NCT02151526 | Completed (March 10, 2020) | Lentiviral β-A-T87Q globin vector | Results published: DOI: 10.1056/NEJMoa1609677 |
| A study evaluating the safety and efficacy of the LentiGlobin BB305 drug product in severe SCD | NCT02140554 | Active, not recruitinga | BB305 lentiviral vector encoding the human β-A-T87Q globin gene | NCT03207009 and NCT02906202 related but for patients with β-thalassemia |
| Gene transfer for patients with SCD | NCT02186418 | Active, not recruiting | Autologous CD34+ hematopoietic stem cells transduced ex vivo with gamma-globin lentiviral vector | |
| Safety and feasibility of gene therapy with CSL200 | NCT04091737 | Active, not recruiting | Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and shRNA734 | |
| Stem cell gene therapy for SCD | NCT02247843 | Recruiting | βAS3 lentiviral vector-modified autologous peripheral blood stem cell transplant | |
| Safety and efficacy of gene therapy of the SCD with the lentiviral vector expressing the βAS3 globin gene in patients with SCD | NCT03964792 | Recruiting | Consists of autologous human CD34+ hematopoietic stem and progenitor cells that are enriched in CD34+ cells which have been transduced ex vivo with the lentiviral vector, expressing an βAS3 | |
| Gene transfer for SCD | NCT03282656 | Suspendedb | Lentiviral anti-BCL11A shRNA | Study paused per DSMB pending investigation of adverse event occurrence in an unrelated gene therapy study involving sickle cell patients (last update February 2021) |
| A study evaluating gene therapy with BB305 lentiviral vector in SCD | NCT04293185 | Suspendedb | CD34+ hematopoietic stem cells collected by plerixafor mobilization and apheresis, transduced with BB305 lentiviral vector encoding the human β-A-T87Q globin gene | Study suspended due to the occurrence of a suspected unexpected serious adverse reaction (last update March 2021) |
| Gene therapies using gene editing techniques | ||||
| Transplantation of CRISPR/Cas-9 corrected hematopoietic stem cells (CRISPR_SCD001) in patients with severe SCD | NCT04774536 | Not yet recruiting | Autologous CD34+ cell-enriched population that contains cells modified by the CRISPR/Cas-9 ribonucleoprotein | |
| Safety and efficacy of CRISPR/Cas-9 modified CD34+ hHSPCs | NCT03745287 | Recruiting | Autologous CD34+ hHSPCs modified with CRISPR/Cas-9 at the erythroid lineage-specific enhancer of the BCL11A gene | |
| Safety, tolerability, and efficacy of BIVV003 for autologous hematopoietic stem cell transplantation in patients with severe SCD | NCT03653247 | Recruiting | CD34+ cells transfected ex vivo with zinc finger nuclease messenger ribonucleic acid targeting the BCL11A locus | |
| Safety and efficacy of genome-edited hematopoietic stem and progenitor cells in SCD | NCT04443907 | Recruiting | Genome-edited autologous HSPC investigational drug product. Drugs: OTQ923 and HIX763 | Part C would include pediatric patients that received one of both experimental drugs |
aCurrently not recruiting due to 2 long-term follow-up patients developed myeloid malignancies.
bCurrently suspended due to findings of NCT02140554.
βAS3 = anti-sickling beta globin gene βAS3; BCL11A = B-cell lymphoma/leukemia 11A; CRISPR/Cas-9 = clustered regularly interspaced short palindromic repeats/CRISPR (C) associated nuclease-9; DSMB = Data and Safety Monitoring Board; hHSPCs = human hematopoietic stem and progenitor cells; SCD = sickle cell disease; shRNA = short hairpin RNA.