EDIT-301 for Beta Thalassemia

Not currently recruiting at 7 trial locations

Overseen By Editas Medicine Clinical Trial Team

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Editas Medicine, Inc.

Disqualifiers: Alpha thalassemia, Hemoglobinopathy, 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: 1

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, a gene-editing therapy, for individuals with Transfusion Dependent beta Thalassemia, a condition requiring regular blood transfusions to manage low red blood cell levels. The goal is to determine if this treatment is safe and effective as a one-time infusion. EDIT-301 may suit those who have needed frequent blood transfusions for at least two years and are medically stable enough to receive the treatment. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

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

Research has shown that EDIT-301 appears safe for humans. Studies found no serious side effects after patients received the EDIT-301 infusion, and importantly, none were linked to the treatment itself.

This treatment uses gene editing to assist people with beta thalassemia, a condition where the body doesn't produce enough healthy red blood cells. After receiving EDIT-301, patients demonstrated normal hemoglobin levels and increased fetal hemoglobin, reducing the need for blood transfusions. These results suggest that EDIT-301 is well-tolerated and safe for people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

EDIT-301 is unique because it uses autologous gene-edited hematopoietic stem cells to treat beta thalassemia. Unlike traditional treatments like regular blood transfusions and iron chelation therapy, which manage symptoms, EDIT-301 targets the root cause by editing the patient's own stem cells to produce healthy red blood cells. This one-time intravenous infusion offers the potential for long-term benefits and possibly even a cure, which is why researchers are excited about its promise.

What evidence suggests that EDIT-301 might be an effective treatment for beta Thalassemia?

Studies have shown promising results for EDIT-301 in treating people with beta thalassemia who need regular blood transfusions. Patients receiving EDIT-301 reached normal hemoglobin levels and high levels of fetal hemoglobin, a type typically found in newborns but not adults. In early research, edited stem cells improved red blood cell production and showed strong results. This treatment uses gene editing to activate certain genes that help reduce beta thalassemia symptoms. These initial findings suggest that EDIT-301 could be an important step forward in managing this condition. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with Transfusion-Dependent Beta Thalassemia, who have needed regular blood transfusions and are in stable condition to undergo a stem cell transplant. They should not have had previous transplants or gene therapy, no significant organ issues, infections, other hemoglobin disorders, cancer or immunodeficiency.

Inclusion Criteria

I am healthy enough for a stem cell transplant using my own cells.

I have been diagnosed with Transfusion Dependent B-Thalassemia.

I am mostly able to care for myself.

Exclusion Criteria

My organs are not functioning properly.

I have a donor who is a perfect match for my bone marrow transplant.

I have had a stem cell transplant or cannot have one due to health reasons.

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 EDIT-301 via intravenous infusion

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including HSPC engraftment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• EDIT-301

Trial Overview The study tests EDIT-301's safety and effectiveness in treating Beta Thalassemia. Participants will receive this treatment before undergoing an autologous Hematopoietic Stem Cell Transplant (HSCT), where they use their own stem cells.

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+

Published Research Related to This Trial

β-thalassemia intermedia (β-TI) is a complex condition characterized by varying levels of anemia, and its management includes traditional treatments like transfusion therapy and splenectomy, as well as newer approaches such as genome editing and novel erythropoiesis-stimulating agents.

Recent advancements in molecular therapies, including CRISPR/Cas9 and epigenetic modulation, show promise in improving treatment outcomes for β-TI by targeting the underlying genetic causes of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Expert Overview on Therapies in Non-Transfusion-Dependent Thalassemia: Classical to Cutting Edge in Treatment. Saeidnia, M., Fazeli, P., Farzi, A., et al.[2023]

Genetic polymorphisms and mutations significantly influence the severity and clinical manifestations of β-thalassemia, including the need for blood transfusions, as identified through a review of relevant studies since 1982.

Increased production of hemoglobin F, influenced by specific genetic alterations, can alleviate symptoms of β-thalassemia, suggesting that understanding these genetic factors can help in predicting disease prognosis and guiding early interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Influence of Polymorphisms in Disease Severity in β-Thalassemia. Mohammdai-Asl, J., Ramezani, A., Norozi, F., et al.[2015]

A novel mutation in the promoter region of the β-globin gene, identified as HBB: c.-127G > C, was discovered in a family with suspected β-globin mutations, indicating its potential role in β-thalassemia.

The study found that this mutation is associated with a mild phenotype of β-thalassemia, as evidenced by hematological and clinical evaluations of the family members carrying the mutation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Mutation in the Promoter Region of the β-Globin Gene: HBB: c.-127G > C. Bilgen, T., Canatan, D., Delibas, S., et al.[2017]

A new base editing strategy has been developed that can correct the HbE mutation responsible for severe β-thalassaemia, achieving over 90% editing efficiency in primary human CD34+ cells.

This approach not only targets the mutation effectively but also demonstrates safety by profiling off-target effects and using machine-learning methods to predict potential impacts, indicating a promising avenue for treating or preventing severe thalassaemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct correction of haemoglobin E β-thalassaemia using base editors. Badat, M., Ejaz, A., Hua, P., et al.[2023]

A new β(0) frameshift mutation (HBB: c.44delT) was identified in a family with β-Thalassemia intermedia, highlighting the genetic complexity of the condition.

The study emphasizes the role of secondary genetic modifiers in influencing the severity of β-Thalassemia intermedia, which can help in better identifying and understanding the disease within families.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new β(0) frameshift mutation, HBB: c.44delT (p.Leu14ArgfsX5), identified in an Argentinean family associated with secondary genetic modifiers of β-thalassemia. Pepe, C., Eberle, SE., Chaves, A., et al.[2014]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05444894

Study Details | NCT05444894 | EDIT-301 for Autologous ... EDIT-301 (autologous gene edited (CD)34+ hematopoietic stem cells) will be administered as a one-time intravenous infusion. Intervention/Treatment, Genetic : ...

2. 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%.

3. sciencedirect.com sciencedirect.com/science/article/pii/S266663672302047X

311 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 ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/PMC10428393

S272: SAFETY AND EFFICACY OF RM-001 IN PATIENTS ... Using gene editing to mimic these mutations should reactivate γ-globin in patients with transfusion-dependent β-thalassemia (TDT) and ameliorate the symptoms of ...

5. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4960/533967/Updated-Safety-and-Efficacy-Results-of-RM-001

Updated Safety and Efficacy Results of RM-001, Autologous ... The data from 19 TDT pts infused with RM-001 demonstrated clinically meaningful and sustained increases in total Hb and HbF, leading to ...

6. thalassaemia.org.cy thalassaemia.org.cy/clinical-trial-updates/edit-301-gene-editing-2/

reni-cel (EDIT-301) – TIF No serious adverse events occurred after EDIT-301 infusion, and no adverse events reported were related to treatment with EDIT-301.

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

AsCas12a Gene Editing of HBG1/2 Promoters with ... EDIT-301 gene editing resulted in sustained normalization of hemoglobin, increased fetal hemoglobin, and transfusion independence in some patients.

8. ir.editasmedicine.com ir.editasmedicine.com/news-releases/news-release-details/editas-medicine-announces-positive-initial-edit-301-safety-and

Editas Medicine Announces Positive Initial EDIT-301 ... In the RUBY trial, Patients 1 and 2 reached normal hemoglobin levels five months post-treatment with EDIT-301, and both patients have maintained ...