BEACON: A Study Evaluating the Safety and Efficacy of BEAM-101 in Patients With Severe Sickle Cell Disease

Study Overview
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Brief Summary
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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

Official Title
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A Phase 1/2 Study Evaluating the Safety and Efficacy of a Single Dose of Autologous CD34+ Base Edited Hematopoietic Stem Cells (BEAM-101) to Increase Fetal Hemoglobin (HbF) Production in Patients With Severe Sickle Cell Disease

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Biological: BEAM-101


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria Include: Age ≥18 years to ≤35 years for the initial sentinel cohort; for subsequent enrollment patients from ≥12 years up to ≤35 years may be enrolled only upon approval by FDA. Documented diagnosis of sickle cell disease with βS/βS, βS/β0, or βS/β+ genotypes. 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: HbF levels >20%, obtained at the time of screening on or off hydroxyurea therapy Previous receipt of an autologous or allogeneic HSCT or solid organ transplantation Available and willing matched sibling donor Definitive diagnosis of moyamoya syndrome based on screening brain MRA History of overt stroke

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BEAM-101<br>BEAM-101 manufactured with autologous CD34+ hematopoietic stem cells collected by plerixafor mobilization and edited ex vivo. No maximum dose has been set for BEAM-101; all of the gene edited cells that pass release specifications will be administered to the patient. BEAM 101 will be administered as a single dose by IV infusion. | Biological: BEAM-101<br>* Single dose of BEAM-101 administered by IV following myeloablative conditioning with busulfan<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| Change in free Hgb over time |  | Month 3 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gene Editing, Sickle Cell, Severe Sickle Cell