Hemoglobin Disorders > EDIT-301

EDIT-301 for Beta Thalassemia

Recruiting in Palo Alto (17 mi)

+7 other locations

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Editas Medicine, Inc.

Disqualifiers: Alpha thalassemia, Hemoglobinopathy, Malignancy, others

No Placebo Group

Approved in 2 jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment called EDIT-301, which modifies a patient's own stem cells to treat severe beta Thalassemia. It targets adults who need regular blood transfusions. The goal is to fix their cells so they can produce healthy blood cells and reduce the need for transfusions.

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.

What makes the treatment EDIT-301 unique for beta thalassemia?

EDIT-301 is unique because it uses genome editing to directly correct genetic mutations causing beta thalassemia, potentially offering a more targeted and long-lasting solution compared to traditional treatments like blood transfusions or iron chelation therapy.

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Eligibility Criteria

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.

Trial Timeline

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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Columbia University Medical Center New York, NY

Cleveland Clinic Cleveland, OH

Columbia University Medical Center - Department of Pediatrics New York, NY

Princess Margaret Cancer Centre-University Health Network Toronto, Canada

More Trial Locations

Who Is Running the Clinical Trial?

Editas Medicine, Inc. Lead Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

A Novel Mutation in the Promoter Region of the β-Globin Gene: HBB: c.-127G > C. [2017] Novel β-globin gene mutations are still occasionally being reported, especially when evaluating milder phenotypes. We report here a novel putative mutation in the promoter region of the β-globin gene and assess its clinical implications. A family, parents and four siblings, with hematological and clinical features suspected of being β-globin gene mutation(s), were involved in this study. In addition to hematological and clinical evaluations of the whole family, molecular analyses of the β-globin gene were performed by direct sequencing. Sequencing of the β-globin gene revealed a novel genomic alteration in the regulatory region of the gene. This novel genomic alteration was defined as HBB: c.-127G > C according to the Human Genome Variation Society (HGVS) nomenclature. Two siblings were found to be carriers of the HBB: c.-127G > C mutation, while the other two siblings were carriers of the codon 8 (-AA) (HBB: c.25_26delAA) deletion of the β-globin gene. The mother was a compound heterozygote for the codon 8 and HBB: c.-127G > C mutations. Based on hematological and clinical evaluations, we conclude that this novel β-globin gene promoter region change would be associated with a mild phenotype of β-thalassemia (β-thal).

2. England 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. [2014] β-Thalassemia intermedia (β-TI) patients present with a wide spectrum of phenotypes depending on the presence of primary, secondary, and tertiary genetic modifiers which modulate, by different mechanisms, the degree of imbalance between α and β chains. Here we describe a new β(0) frameshift mutation, HBB: c.44delT (p.Leu14ArgfsX5), identified in four members of a family, associated with secondary genetic modifiers in three of them. The different genotype present in this family was suspected after hematological analysis and thorough observation of blood smears highlighting their importance in the identification of β-TI patients among members of the same family.

3. England pubmed.ncbi.nlm.nih.gov

Direct correction of haemoglobin E β-thalassaemia using base editors. [2023] Haemoglobin E (HbE) β-thalassaemia causes approximately 50% of all severe thalassaemia worldwide; equating to around 30,000 births per year. HbE β-thalassaemia is due to a point mutation in codon 26 of the human HBB gene on one allele (GAG; glutamatic acid → AAG; lysine, E26K), and any mutation causing severe β-thalassaemia on the other. When inherited together in compound heterozygosity these mutations can cause a severe thalassaemic phenotype. However, if only one allele is mutated individuals are carriers for the respective mutation and have an asymptomatic phenotype (β-thalassaemia trait). Here we describe a base editing strategy which corrects the HbE mutation either to wildtype (WT) or a normal variant haemoglobin (E26G) known as Hb Aubenas and thereby recreates the asymptomatic trait phenotype. We have achieved editing efficiencies in excess of 90% in primary human CD34 + cells. We demonstrate editing of long-term repopulating haematopoietic stem cells (LT-HSCs) using serial xenotransplantation in NSG mice. We have profiled the off-target effects using a combination of circularization for in vitro reporting of cleavage effects by sequencing (CIRCLE-seq) and deep targeted capture and have developed machine-learning based methods to predict functional effects of candidate off-target mutations.

4. England pubmed.ncbi.nlm.nih.gov

An Expert Overview on Therapies in Non-Transfusion-Dependent Thalassemia: Classical to Cutting Edge in Treatment. [2023] The thalassemia issue is a growing worldwide health concern that anticipates the number of patients suffering from the disease will soon increase significantly. Patients with β-thalassemia intermedia (β-TI) manifest mild to intermediate levels of anemia, which is a reason for it to be clinically located between thalassemia minor and β-thalassemia major (β-TM). Notably, the determination of the actual rate of β-TI is more complicated than β-TM. The leading cause of this illness could be partial repression of β-globin protein production; accordingly, the rate of β-globin gene repression is different in patients, and the gene repression intensity creates a different clinical status. This review article provides an overview of functional mechanisms, advantages, and disadvantages of the classic to latest new treatments for this group of patients, depending on the disease severity divided into the typical management strategies for patients with β-TI such as fetal hemoglobin (Hb) induction, splenectomy, bone marrow transplantation (BMT), transfusion therapy, and herbal and chemical iron chelators. Recently, novel erythropoiesis-stimulating agents have been added. Novel strategies are subclassified into molecular and cellular interventions. Genome editing is one of the efficient molecular therapies for improving hemoglobinopathies, especially β-TI. It encompasses high-fidelity DNA repair (HDR), base and prime editing, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 procedure, nuclease-free strategies, and epigenetic modulation. In cellular interventions, we mentioned the approach pattern to improve erythropoiesis impairments in translational models and patients with β-TI that involve activin II receptor traps, Janus-associated kinase 2 (JAK2) inhibitors, and iron metabolism regulation.

5. United States pubmed.ncbi.nlm.nih.gov

The Influence of Polymorphisms in Disease Severity in β-Thalassemia. [2015] β-Thalassemia is a genetic disorder with a continuum of mild to severe clinical manifestations and requirement of transfusion at different stages of life. The cause(s) of this variety is not clear but genetic alterations could be a potential factor. In this review, the correlation between polymorphisms and different clinical manifestations, including the need for transfusion, was investigated. Relevant articles published in pubmed database from 1982 onwards were studied and compiled. The articles all contained the keywords β-thalassemia, genetic modifiers, and mutations. Certain polymorphisms and mutations could dictate the severity of symptoms as well as their onset. A significant number of the mentioned genetic alterations appear in beta-globin gene cluster and affect gamma chain. Therefore, hemoglobin F production rate is increased and can affect thalassemia symptoms and can relieve β-thalassemia symptoms. A number of polymorphisms in catalase and glutathione S transferase genes have also been shown to modify the severity of disease and response to treatment. Knowledge of these mutations and polymorphisms can provide an insight into the prognosis for individual patients, especially in young ages or before birth to take proper measures in advance and eventually ameliorate the symptoms in the long run.