This study will use base editing to restore fetal hemoglobin (HbF) production in patients with severe sickle cell disease (SCD) and ameliorate clinical symptoms.
Allogeneic hematopoietic stem cell transplant is the only known cure for SCD. However, the procedure is only available to about 20% of patients who have matched donors and carries the risk of graft-versus-host disease. Approved therapies to prevent SCD complications include hydroxyurea and L-glutamine oral powder, but patients can still have breakthrough vaso-occlusive crises.
The base editing therapeutic approach aims to restore HbF production by introducing changes into the HBG1 and HBG2 promoters. These changes reduce the ability of the naturally occurring protein BCL11A, to associate with HBG1/2, leading to switching HbF back on.
St. Jude is one of several sites for the BHEEM trial sponsored by BEAM Therapeutics Inc.
To determine the safety and clinical efficacy of a single dose of autologous gene-edited CD34+ hematopoietic stem cell and progenitor cells (BEAM-101) in patients with severe sickle cell disease.
Inclusion criteria include:
- 18–35 years old
- Diagnosis of severe sickle cell disease
- Documented βS/βS βS/β0, or βS/β+ genotype
- Willingness to discontinue hydroxyurea at least 30 days prior to stem cell mobilization through Day 100 after transplantation.
Exclusion criteria include:
- Available and willing matched sibling donor
- Prior hematopoietic stem cell transplant
- Clinically significant and active bacterial, viral, fungal, or parasitic infection
St. Jude Children’s Research Hospital, Memphis, Tennessee
Collaborating sites in and outside the U.S.
About this study
This is a clinical trial to learn about the safety and possible side effects of BEAM-101 in patients with severe sickle cell disease (SCD).
BEAM-101 is investigational. That means the U.S. Food and Drug Administration (FDA) has not yet approved it. We want to see if a single dose of BEAM-101 helps your body to:
- Increase the amount of a type of hemoglobin called hemoglobin F. Hemoglobin is a protein in red blood cells that delivers oxygen to the body’s cells.
- Decrease the effects of SCD
Main steps of the study:
- We collect bone marrow cells (stem cells) from you.
- We send those cells to a lab. In the lab, we change (edit) the DNA of a specific gene in your cells. This creates a study product called BEAM-101. The technology used to edit the DNA is called base editing. It introduces certain changes to the DNA. We hope this repair will help your body make more hemoglobin F.
- You will get an autologous bone marrow transplant using your changed cells. This transplant takes place in the hospital. You will take medicine to remove your bone marrow cells and create “room” for the edited cells. We will put the modified cells into your vein with an IV.
- We hope that once the changed cells are in the body, the red blood cells will no longer sickle or cause complications of sickle cell disease.
Purpose of this clinical trial
The main goal of this study is to see if a single dose of BEAM-101 allows your body to increase the amount of hemoglobin F while reducing the painful effects of sickle cell disease.
- 18–35 years old
- Diagnosed with severe sickle cell disease
BHEEM Quick View Sponsor BEAM Therapeutics Inc. ClinicalTrials.gov Identifier NCT05456880 Trial start date April 2023 Estimated enrollment
Study type Interventional Study Phase 1/2 Conditions
Sickle Cell Disease
Ages 18-35 years old Site Principal Investigator
Akshay Sharma, MBBS
Study site St. Jude Children’s Research Hospital and collaborating sites in and outside the U.S. For a consultation or to discuss BHEEM St. Jude Physician/Patient Referral Office
St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105 USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334
The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.