Hemoglobinopathies, Sickle Cell Disease
Conditions
Keywords
Anemia, Anemia, Sickle Cell, Anemia, Hemolytic, Congenital, Anemia, Hemolytic, Genetic Diseases, Inborn, Cell Disorders, Sickle, HbS Disease, Sickling Disorder Due to Hemoglobin S, Hematologic Diseases
Brief summary
The purpose of this study is to evaluate the efficacy, safety and tolerability of treatment with EDIT-301 in adult and adolescent participants with severe sickle cell disease (SCD).
Detailed description
This is a Phase 1/2 single-arm, open-label, multicenter study evaluating the safety and efficacy of a single unit dose of EDIT-301 for autologous hematopoietic stem cell transplant (HSCT) in subjects with severe SCD. Planned study subjects will be comprised of male and female adult and adolescent subjects with severe SCD, from 12 to 50 years of age, inclusive.
Interventions
GENETICEDIT-301
Administered by IV infusion after myeloablative conditioning with busulfan.
Sponsors
Editas Medicine, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: Diagnosis of severe sickle cell disease as defined by: * Documented SCD genotype (βS/βS, βS/β0, βS/β+, or others) and * History of at least two severe vaso-occlusive events per year requiring medical attention despite hydroxyurea or other supportive care measures in the two year-period prior to provision of informed consent or assent, as applicable Karnofsky (for subjects \>16 years of age) or Lansky (for subjects ≤ 16 years of age) Performance Status ≥ 80% Normal transcranial doppler velocity in subjects 16 years of age or younger Key
Exclusion criteria
* Available 10/10 HLA-matched related donor * Prior HSCT or contraindications to autologous HSCT * Any contraindications to the use of plerixafor during the mobilization of hematopoietic stem cells (HSCs) and any contraindications to the use of busulfan and any other medicinal products required during the myeloablative conditioning, including hypersensitivity to the active substances or to any of the excipients * Unable to receive red blood cell (RBC) transfusion for any reason * Unable or unwilling to comply with standard of care changes in background medical treatment in preparation of, during, or following HSCT, including and not limited to discontinuation of hydroxyurea, voxelotor, crizanlizumab, or L-glutamine * Any history of severe cerebral vasculopathy * Inadequate end organ function * Advanced liver disease * Any prior or current malignancy or immunodeficiency disorder * Immediate family member with a known or suspected Familial Cancer Syndrome * Clinically significant and active bacterial, viral, fungal, or parasitic infection Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of subjects achieving complete resolution of severe vaso-occlusive events (VOEs) | from Month 6 through Month 18 post EDIT-301 infusion |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of subjects with 90% reduction in annualized rate of severe VOE compared to pre-treatment period | starting from 6 months up to 2 years post EDIT-301 infusion |
| Proportion of subjects with 75% reduction in annualized rate of severe VOE compared to pre-treatment period | starting from 6 months up to 2 years post EDIT-301 infusion |
| Proportion of subjects with 50% reduction in annualized rate of severe VOE compared to pre-treatment period | starting from 6 months up to 2 years post EDIT-301 infusion |
| Difference (pre-treatment vs. post-treatment) in annualized rates of severe VOEs | starting from 6 months up to 2 years post EDIT-301 infusion |
| Difference (pre-treatment vs. post-treatment) in annualized rate of hospitalization for severe VOEs | starting from 6 months up to 2 years post EDIT-301 infusion |
| Proportion of subjects with sustained HbF ≥ 20% (HbF/Hb) compared with baseline | starting from 6 months up to 2 years post EDIT-301 infusion |
| Proportion of subjects with mean HbF ≥ 30% (HbF/Hb) compared with baseline | starting from 6 months up to 2 years post EDIT-301 infusion |
| Proportion of subjects with mean total Hb ≥ 10 g/dL compared with baseline | starting from 6 months up to 2 years post EDIT-301 infusion |
| Proportion of subjects achieving complete resolution of VOEs | from Month 6 through Month 18 post EDIT-301 infusion |
| Difference (pre-treatment versus post-treatment) in annualized number of units of pRBC transfused for SCD-related indications | starting from 6 months up to 2 years post EDIT-301 infusion |
| Change from baseline in HbF concentration (g/dL) | up to 2 years post EDIT-301 infusion |
| Change from baseline in total Hb concentration (g/dL) | up to 2 years post EDIT-301 infusion |
| Change from baseline in markers of hemolysis (absolute reticulocyte count, indirect bilirubin, lactate dehydrogenase, haptoglobin) | up to 2 years post EDIT-301 infusion |
| Time to neutrophil engraftment (the first day in which 3 consecutive absolute neutrophil count (ANC) ≥ 0.5 x 109/L laboratory values obtained on different days) | up to 24 months after EDIT-301 infusion |
| Time to platelet engraftment (the first day in which 3 consecutive platelets ≥ 50 x 109/L laboratory values obtained for at least 7 days following the last platelet transfusion and 10 days following any administration of thrombopoietin (TPO) mimetics) | up to 24 months after EDIT-301 infusion |
| Frequency and severity of adverse events (AEs) | up to 24 months post EDIT-301 infusion |
| Proportion of subjects with mean total Hb increase from baseline of ≥ 2 g/dL | starting from 6 months up to 2 years post EDIT-301 infusion |
Countries
Canada, United States
Outcome results
None listed