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

Overview

About this study

The purpose of this study is to evaluate the safety and efficacy of a single dose of ex vivo base-edited, autologous CD34+ human hematopoietic stem and progenitor cells (HSPCs) in patients with SCD and severe VOCs. Like allogenic HSCT, these therapies are designed to replace the patient’s bone marrow (BM) with hematopoietic stem cells (HSCs) that encode nonsickling globins. However, as an autologous therapy, BEAM-101 (the IMP in this study) has the potential advantages of eliminating the morbidity and mortality of graft-versus-host disease (GVHD) and greatly broadening access to the majority of patients who lack a matched sibling donor.

BEAM-101 utilizes base editing to introduce specific point mutations that are designed to induce the expression of therapeutic, nonsickling hemoglobin (Hb). BEAM-101 introduces point mutations in the HBG1 and HBG2 promoters, which mimic naturally occurring mutations that disrupt binding of B-cell lymphoma/leukemia 11A gene (BCL11A), a transcriptional repressor of fetal hemoglobin (HbF). Individuals with these mutations have the condition known as hereditary persistence of fetal hemoglobin (HPFH) and continue to have nonsickling HbF expression throughout their life.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

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

Exclusion Criteria:

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 Magnetic Resonance Angiography (MRA).
History of overt stroke.

Eligibility last updated 4/27/23. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location	Status	Contact
Jacksonville, Fla. Mayo Clinic principal investigator Ernesto Ayala, M.D.	Open for enrollment	Contact information: Clinical Studies Unit (904) 953-2255

Mayo Clinic Location

Status

Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Ernesto Ayala, M.D.

Open for enrollment

Contact information:

Clinical Studies Unit

(904) 953-2255

More information

Publications

Publications are currently not available

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