RUBY Trial of Gene Editing Cell Therapy EDIT-301 Now Enrolling
Enrollment is underway for a Phase 1/2 trial evaluating the safety and efficacy of EDIT-301, an experimental gene editing cell therapy for people with sickle cell disease (SCD).
EDIT-301 is a one-time gene editing cell therapy designed to increase the production of fetal hemoglobin, known as HbF, in red blood cells by modifying a patient’s blood cell precursors, called hematopoietic stem cells. Fetal hemoglobin is a type of hemoglobin found in newborns that is more efficient at transporting oxygen than the version found in adults.
For this therapy, hematopoietic stem cells are first collected from the patient and then genetically modified via the gene-editing tool CRISPR/Cas12a (also known as CRISPR-Cpf1). The modified step cells are ultimately returned to the patient in the form of a stem cell transplant.
According to the company, red blood cells derived from stem cells genetically modified with EDIT-301 have demonstrated a sustained increase in HbF production, with the potential to provide a one-time, durable benefit for people with SCD.
The ultimate goal, Editas says, is to improve blood flow and reduce vaso-occlusive crises — a painful complication in SCD caused by sickled red blood cells sticking to and blocking circulation in small blood vessels.
RUBY is a single-arm, open-label study that is designed to evaluate the safety and efficacy of a single dose of EDIT-301 in up to 40 patients, ages 18–50, with severe SCD. More information on study locations and contacts can be found here.
To be eligible, participants must have a history of at least two severe vaso-occlusive crises per year requiring medical attention despite treatment with hydroxyurea — a therapy used to lower the frequency of pain crises — or other care measures in the two years prior.
Participants will receive a single dose of EDIT-301 intravenously, or directly into the bloodstream, after completing myeloablative conditioning treatment with busulfan. That treatment is a method used to clear patients of “defective” blood-forming cells in preparation for the introduction of the modified stem cells.
The study’s primary goal is to assess changes in the rate of severe vaso-occlusive events (VOEs) requiring medical attention for up to two years post-infusion.
One secondary outcome is to assess the proportion of SCD patients with a mean HbF increase of more than 20% following EDIT-301. Another secondary outcome, or endpoint, is the proportion of participants with a mean hemoglobin level equal to or greater than 10 g/dL starting 60 or more days after the last red blood cell transfusion.
The total number of red blood cell units used in transfusions for SCD-related complications, as well as changes in the annualized rate of hospitalizations for severe VOEs, also will be determined.
EDIT-301 has been granted rare pediatric disease designation, which is given to experimental therapies aiming to treat serious or life-threatening conditions affecting fewer than 200,000 pediatric patients in the U.S.
This gene editing cell therapy also is being investigated as a potential treatment for people with transfusion-dependent beta thalassemia, an inherited blood disorder that reduces the production of hemoglobin.