Back to resultsEDIT-301 for Autologous Hematopoietic Stem Cell Transplant (HSCT) in Participants With Transfusion-Dependent Beta Thalassemia (TDT)
Primary Purpose
Transfusion Dependent Beta Thalassemia, Hemoglobinopathies, Thalassemia Major
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
EDIT-301
Sponsored by
About this trial
This is an interventional treatment trial for Transfusion Dependent Beta Thalassemia focused on measuring Beta-Thalassemia, Hemoglobinopathies, CRISPR-Cas 12a, Autologous CD34+
Eligibility Criteria
Key Inclusion Criteria:
Diagnosis of Transfusion Dependent B-Thalassemia as defined by:
- Documented homozygous β-thalassemia or compound heterozygous β-thalassemia including β-thalassemia/hemoglobin E (HbE) based on historical data in medical records, and
- History of at least 100 mL/kg/year or 10 U/year of packed red blood cell (RBC) transfusions in the 2 years prior to signing informed consent
- Clinically stable and eligible to undergo autologous HSCT
- Karnofsky Performance Status ≥ 70
Key Exclusion Criteria:
- Available 10/10 human leukocyte antigen (HLA)-matched related donor
- Prior HSCT or contraindications to autologous HSCT
- Participants with associated a history of α-thalassemia and > 1 alpha chain deletion, or alpha multiplications as documented in medical records
- Participants with a history of other inherited hemoglobinopathy or thalassemic mutation (Hb S, C, D or other) as documented in medical records
- Prior receipt of gene therapy
- Inadequate bone marrow function, as defined by white blood cell count of < 3 x 10^9/L or a platelet count < 100 x 10^9/L (without hypersplenism), per investigator judgement
- Inadequate organ function
- Advanced liver disease
- Any prior or current malignancy, or immunodeficiency disorder,
- Immediate family member with a known or suspected Familial Cancer Syndrome
- Clinically significant and active bacterial, viral, fungal, or parasitic infection
Sites / Locations
- University of California San FranciscoRecruiting
- University of MinnesotaRecruiting
- Columbia University Medical Center - Department of PediatricsRecruiting
- Columbia University Medical CenterRecruiting
- Cleveland ClinicRecruiting
- Children's Hospital of PhiladelphiaRecruiting
- Tristar Medical Group Children's Specialists/Sarah Cannon Center for Blood CancersRecruiting
- Princess Margaret Cancer Centre-University Health NetworkRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
EDIT-301
Arm Description
EDIT-301 (autologous gene edited (CD)34+ hematopoietic stem cells) will be administered as a one-time intravenous infusion.
Outcomes
Primary Outcome Measures
Proportion of participants achieving engraftment defined as neutrophil engraftment (defined as demonstrating absolute neutrophil count (ANC) ≥ 0.5 x 10^9/L post EDIT-301 infusion for 3 consecutive measurements obtained on different days)
Frequency and severity of adverse events (AEs) (incidence of AEs and Grade 3 or higher serious adverse events, using National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v.5.0)
Secondary Outcome Measures
Kinetics of HSPC engraftment
Time to neutrophil engraftment
Kinetics of HSPC engraftment
Time to platelet engraftment
Incidence of transplant related mortality
Incidence of all-cause mortality
Proportion of alleles per participant with intended genetic modification present in peripheral blood over time
Proportion of alleles per participant with intended genetic modification present in bone marrow cells over time
Change in the fetal hemoglobin (HbF) concentration compared to baseline overtime
Change in the total hemoglobin concentration compared to baseline overtime
Proportion of participants with hemoglobin concentration ≥ 9 g/dL
Proportion of participants achieving the sustained transfusion reduction (TR) for at least 6 months and at least 12 months from 3 months post-EDIT-301 infusion
Proportion of participants achieving the sustained transfusion independence (TI) for at least 6 months and, at least 12 months from 3 months post EDIT-301 infusion
Change in parameters of iron overload compared to baseline over time
Proportion of participants receiving iron chelation therapy over time
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05444894
Brief Title
EDIT-301 for Autologous Hematopoietic Stem Cell Transplant (HSCT) in Participants With Transfusion-Dependent Beta Thalassemia (TDT)
Official Title
A Multicenter Study to Evaluate the Safety, Tolerability, and Efficacy of a Single Dose of Autologous Clustered Regularly Interspaced Short Palindromic Repeats Gene-edited Cluster of Differentiation 34 (CD34+) Human Hematopoietic Stem and Progenitor Cells (HSPC) (EDIT-301) in Transfusion-Dependent Beta Thalassemia (TDT)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 29, 2022 (Actual)
Primary Completion Date
September 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Editas Medicine, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety, tolerability, and efficacy of treatment with EDIT-301 in adult participants with Transfusion Dependent beta Thalassemia
Detailed Description
This is a Phase 1/2 single-arm, open-label, multicenter study evaluating the safety, tolerability, and efficacy of a single unit dose of EDIT-301 for autologous hematopoietic stem cell transplant in adult participants with TDT, age 18 to 35 years, inclusive
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Transfusion Dependent Beta Thalassemia, Hemoglobinopathies, Thalassemia Major, Thalassemia Intermedia
Keywords
Beta-Thalassemia, Hemoglobinopathies, CRISPR-Cas 12a, Autologous CD34+
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
EDIT-301
Arm Type
Experimental
Arm Description
EDIT-301 (autologous gene edited (CD)34+ hematopoietic stem cells) will be administered as a one-time intravenous infusion.
Intervention Type
Genetic
Intervention Name(s)
EDIT-301
Intervention Description
Administered by intravenous infusion after myeloablative conditioning with busulfan.
Primary Outcome Measure Information:
Title
Proportion of participants achieving engraftment defined as neutrophil engraftment (defined as demonstrating absolute neutrophil count (ANC) ≥ 0.5 x 10^9/L post EDIT-301 infusion for 3 consecutive measurements obtained on different days)
Time Frame
EDIT-301 infusion (Day 0) to 42 days post EDIT-301 infusion
Title
Frequency and severity of adverse events (AEs) (incidence of AEs and Grade 3 or higher serious adverse events, using National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v.5.0)
Time Frame
Screening through up to 24 months post EDIT-301 infusion
Secondary Outcome Measure Information:
Title
Kinetics of HSPC engraftment
Description
Time to neutrophil engraftment
Time Frame
EDIT-301 infusion (Day 0) to first day in which 3 consecutive measurements obtained on different days demonstrate ANC ≥ 0.5 x 10^9/L up to 24 months post EDIT-301 infusion
Title
Kinetics of HSPC engraftment
Description
Time to platelet engraftment
Time Frame
EDIT-301 infusion (Day 0) to first day of 3 consecutive measurements of platelets ≥ 50 x 10^9/L for at least 1 week following the last platelet transfusion and 10 days following thrombopoietin mimetics use up to 24 months post EDIT-301 infusion.
Title
Incidence of transplant related mortality
Time Frame
EDIT-301 infusion (Day 0) through Day 100 post EDIT-301 infusion and from EDIT-301 infusion (Day 0) through 12 months post EDIT-301 infusion
Title
Incidence of all-cause mortality
Time Frame
Screening through up to 24 months post EDIT-301 infusion
Title
Proportion of alleles per participant with intended genetic modification present in peripheral blood over time
Time Frame
EDIT-301 infusion (Day 0) through up to 24 months post EDIT-301 infusion
Title
Proportion of alleles per participant with intended genetic modification present in bone marrow cells over time
Time Frame
EDIT-301 infusion (Day 0) through up to 24 months post EDIT-301 infusion
Title
Change in the fetal hemoglobin (HbF) concentration compared to baseline overtime
Time Frame
Baseline through up to 24 months post EDIT-301 infusion
Title
Change in the total hemoglobin concentration compared to baseline overtime
Time Frame
Baseline through up to 24 months post EDIT-301 infusion
Title
Proportion of participants with hemoglobin concentration ≥ 9 g/dL
Time Frame
EDIT-301 infusion (Day 0) through 3, 6, 12 months up to 24 months post EDIT-301 infusion
Title
Proportion of participants achieving the sustained transfusion reduction (TR) for at least 6 months and at least 12 months from 3 months post-EDIT-301 infusion
Time Frame
3 months post EDIT-301 infusion through up to 24 months post EDIT-301 infusion
Title
Proportion of participants achieving the sustained transfusion independence (TI) for at least 6 months and, at least 12 months from 3 months post EDIT-301 infusion
Time Frame
3 months through up to 24 months post EDIT-301 infusion
Title
Change in parameters of iron overload compared to baseline over time
Time Frame
Baseline through up to 24 months post EDIT-301 infusion
Title
Proportion of participants receiving iron chelation therapy over time
Time Frame
EDIT-301 infusion (Day 0) through up to 24 months post EDIT-301 infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Diagnosis of Transfusion Dependent B-Thalassemia as defined by:
Documented homozygous β-thalassemia or compound heterozygous β-thalassemia including β-thalassemia/hemoglobin E (HbE) based on historical data in medical records, and
History of at least 100 mL/kg/year or 10 U/year of packed red blood cell (RBC) transfusions in the 2 years prior to signing informed consent
Clinically stable and eligible to undergo autologous HSCT
Karnofsky Performance Status ≥ 70
Key Exclusion Criteria:
Available 10/10 human leukocyte antigen (HLA)-matched related donor
Prior HSCT or contraindications to autologous HSCT
Participants with associated a history of α-thalassemia and > 1 alpha chain deletion, or alpha multiplications as documented in medical records
Participants with a history of other inherited hemoglobinopathy or thalassemic mutation (Hb S, C, D or other) as documented in medical records
Prior receipt of gene therapy
Inadequate bone marrow function, as defined by white blood cell count of < 3 x 10^9/L or a platelet count < 100 x 10^9/L (without hypersplenism), per investigator judgement
Inadequate organ function
Advanced liver disease
Any prior or current malignancy, or immunodeficiency disorder,
Immediate family member with a known or suspected Familial Cancer Syndrome
Clinically significant and active bacterial, viral, fungal, or parasitic infection
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Editas Medicine Clinical Trial Team
Phone
617-401-9007
Email
Patients@editasmed.com
Facility Information:
Facility Name
University of California San Francisco
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55410
Country
United States
Individual Site Status
Recruiting
Facility Name
Columbia University Medical Center - Department of Pediatrics
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Name
Tristar Medical Group Children's Specialists/Sarah Cannon Center for Blood Cancers
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Name
Princess Margaret Cancer Centre-University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
EDIT-301 for Autologous Hematopoietic Stem Cell Transplant (HSCT) in Participants With Transfusion-Dependent Beta Thalassemia (TDT)
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