Sickle Cell Disease
Conditions
Keywords
Gene Editing, Sickle Cell, Severe Sickle Cell
Brief summary
This is an open-label, single-arm, multicenter, Phase 1/2 study evaluating the safety and efficacy of the administration of autologous base edited CD34+ HSPCs (BEAM-101) in patients with severe SCD
Interventions
BIOLOGICALBEAM-101
Single dose of BEAM-101 administered by IV following myeloablative conditioning with busulfan
Sponsors
Beam Therapeutics Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria Include: 1. Age ≥12 years to ≤35 years 2. Documented diagnosis of sickle cell disease with βS/βS, βS/β0, or βS/β+ genotypes. 3. Severe SCD defined by the occurrence of at least 4 severe VOCs in the 24 months prior to screening despite receiving hydroxyurea or other supportive care measures Key
Exclusion criteria
Include: 1. HbF levels \>20%, obtained at the time of screening on or off hydroxyurea therapy 2. Previous receipt of an autologous or allogeneic HSCT or solid organ transplantation 3. Available and willing matched sibling donor 4. Definitive diagnosis of moyamoya syndrome based on screening brain MRA 5. History of overt stroke
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in annualized number of severe VOCs (Vascular-occlusive Crisis) relative to baseline | 6 months to time of analysis as compared to baseline |
| Proportion of patients with successful neutrophil engraftment | BEAM-101 administration to month 24 |
| Time to neutrophil engraftment | BEAM-101 administration to month 24 |
| Time to platelet engraftment | BEAM-101 administration to month 24 |
| Transplant-related mortality within 100 days after beam-101 treatment | BEAM-101 administration to day 100 |
| Safety and tolerability assessments based on frequency, severity and seriousness of adverse events (AE's) | BEAM-101 administration through month 24 |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of patients with HbF ≥30%, for at least 3 months | Month 6 post BEAM-101 treatment to month 24 as compared to baseline |
| Change in lactate dehydrogenase (LDH) over time | Month 3 post BEAM-101 treatment to month 24 as compared to baseline |
| Change in total bilirubin over time | Month 3 post BEAM-101 treatment to month 24 as compared to baseline |
| Proportion of patients experiencing at least 75% reduction in annualized rate of severe VOCs | Month 6 post BEAM-101 treatment to month 24 as compared to baseline |
| Change in haptoglobin over time | Month 3 post BEAM-101 treatment to month 24 as compared to baseline |
| Change in reticulocyte count over time | Month 3 post BEAM-101 treatment to month 24 as compared to baseline |
| Change in free Hgb over time | Month 3 post BEAM-101 treatment to month 24 as compared to baseline |
| Proportion of patients experiencing no severe VOCs | 6 months to time of analysis as compared to baseline |
| Change in annualized number of hospitalizations for VOCs | Month 6 post BEAM-101 treatment to month 24 as compared to baseline |
| Change in annualized duration of hospitalizations for VOCs | Month 6 post BEAM-101 treatment to month 24 as compared to baseline |
| Change in RBC transfusions per month and per year for SCD-related indications | Month 2 post BEAM-101 treatment to month 24 as compared to baseline |
| Change in total Hgb (g/dL) concentration over time | Baseline to month 24 |
Countries
United States
Outcome results
None listed