EDIT-301 for Sickle Cell Disease

Not currently recruiting at 25 trial locations

Overseen By Editas Medicine's Clinical Trial Team

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Editas Medicine, Inc.

Must not be taking: Hydroxyurea, Voxelotor, Crizanlizumab, L-glutamine

Disqualifiers: HLA-matched donor, Prior HSCT, Vasculopathy, Malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called EDIT-301 for individuals with severe sickle cell disease (SCD). Researchers aim to determine if this one-time gene therapy can improve symptoms and ensure patient safety. The treatment modifies a person's own stem cells and reintroduces them through an IV. It suits those who experience at least two serious pain crises annually, despite using standard medications like hydroxyurea. As a Phase 1, Phase 2 trial, the study focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from this innovative therapy.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications like hydroxyurea, voxelotor, crizanlizumab, or L-glutamine as part of the trial requirements.

Is there any evidence suggesting that EDIT-301 is likely to be safe for humans?

Research has shown that EDIT-301, a new gene-editing treatment, demonstrates promising safety results in studies with patients who have severe sickle cell disease. The treatment has successfully integrated into the body as expected. Additionally, there has been a steady increase in beneficial blood markers, such as total hemoglobin and fetal hemoglobin, which are crucial for improving sickle cell symptoms.

Importantly, patients tolerate the treatment well, with no major safety concerns reported in the available data. This suggests that unwanted effects are neither common nor severe. While the treatment remains under investigation and more data are needed, these early results offer encouragement for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sickle cell disease?

EDIT-301 is unique because it uses autologous gene-edited hematopoietic stem cells to treat sickle cell disease. Unlike traditional treatments that often rely on regular blood transfusions or hydroxyurea to manage symptoms, EDIT-301 involves a one-time intravenous infusion that directly targets the genetic cause of the disease. Researchers are excited because this approach has the potential to provide a long-lasting solution by correcting the defective gene responsible for sickle cell disease, potentially reducing or eliminating the need for ongoing treatments.

What evidence suggests that EDIT-301 might be an effective treatment for sickle cell disease?

Research has shown that EDIT-301 holds promise for treating severe sickle cell disease (SCD). Early results indicate that the modified cells thrive in the body. Patients have experienced a rapid and lasting increase in total hemoglobin and fetal hemoglobin, both crucial for reducing SCD symptoms. Specifically, all patients with at least five months of follow-up achieved normal hemoglobin levels and fetal hemoglobin levels over 40%. This suggests that EDIT-301 could significantly enhance the health of individuals with SCD. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with severe sickle cell disease who have had at least two major pain episodes per year despite treatment. They must be generally well-functioning (Karnofsky Performance Status ≥ 80). People can't join if they've had a stem cell transplant, have certain allergies or infections, advanced liver disease, cancer, immune disorders, or an HLA-matched donor.

Inclusion Criteria

I have a severe form of sickle cell disease.

I can carry out normal activities with minimal symptoms.

I've had 2 or more severe pain crises a year despite treatment.

Exclusion Criteria

My organs are not functioning properly.

I am not allergic to plerixafor, busulfan, or any related medications.

I have or had another cancer or a condition that weakens my immune system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of autologous gene-edited CD34+ hematopoietic stem cells (EDIT-301) via intravenous infusion

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• EDIT-301

Trial Overview The study tests EDIT-301's effectiveness and safety in treating severe sickle cell disease. Participants will receive this experimental therapy to see how well it works and what side effects it may cause compared to standard treatments.

How Is the Trial Designed?

Group I: EDIT-301 Experimental Treatment 1 Intervention

EDIT-301 (autologous gene edited (CD)34+ hematopoietic stem cells) will be administered as a one-time intravenous infusion.

EDIT-301 is already approved in United States, Canada for the following indications:

Approved in United States as EDIT-301 for:

• None approved yet; currently in clinical trials for Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia

Approved in Canada as EDIT-301 for:

• None approved yet; currently in clinical trials for Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia

Who Is Running the Clinical Trial?

Editas Medicine, Inc.

Lead Sponsor

Trials

5

Recruited

170+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10428233/

S264: EDIT-301 SHOWS PROMISING PRELIMINARY ... These preliminary data demonstrate successful engraftment, a rapid and sustained increase in total Hb, HbF level, and percentage of F-cells, improvements in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04853576

A Study Evaluating the Safety and Efficacy of EDIT-301 in ... The purpose of this study is to evaluate the efficacy, safety and tolerability of treatment with EDIT-301 in adult and adolescent participants with severe ...

3. ir.editasmedicine.com ir.editasmedicine.com/news-releases/news-release-details/editas-medicine-announces-new-edit-301-safety-and-efficacy-data

Editas Medicine Announces New EDIT-301 Safety and ... All RUBY patients with ≥5 months follow-up have achieved a normal hemoglobin level and a fetal hemoglobin level of >40%.

4. astctjournal.org astctjournal.org/article/S2666-6367(23)02047-X/fulltext

AsCas12a Gene Editing of HBG1/2 Promoters with ... In preclinical studies, edited CD34+ cells from patients (pts) with SCD or TDT showed improved erythropoiesis and generated red blood cells (RBCs) with robust ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9180595/

Hematopoietic Stem Cell Gene-Addition/Editing Therapy in ... Autologous hematopoietic stem cell (HSC)-targeted gene therapy provides a one-time cure for various genetic diseases including sickle cell disease (SCD) and ...

6. ir.editasmedicine.com ir.editasmedicine.com/news-releases/news-release-details/editas-medicine-reports-updated-clinical-data-ruby-trial-reni

Editas Medicine Reports Updated Clinical Data from the ... (Nasdaq: EDIT), a leading gene editing company, will present updated safety and efficacy data in 28 patients living with severe sickle cell ...

7. yalemedicine.org yalemedicine.org/clinical-trials/edit-301-for-autologous-hsct-in-subjects-with-severe-sickle-cell-disease

A Phase 1/2 Study to Evaluate the Safety and Efficacy of a ... The purpose of this study is to evaluate the efficacy, safety and tolerability of treatment with EDIT-301 in adult and adolescent participants ...