Clinical trial NCT05444894: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Transfusion Dependent Beta Thalassemia
Hemoglobinopathies
Thalassemia Major
Thalassemia Intermedia
Keywords: Beta-Thalassemia
Hemoglobinopathies
CRISPR-Cas 12a
Autologous CD34+
Lead sponsor: Editas Medicine, Inc.
Sponsor class: INDUSTRY
First posted: 2022-07-06
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: 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)
timeFrame: EDIT-301 infusion (Day 0) to 42 days post EDIT-301 infusion
measure: 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)
timeFrame: Screening through up to 24 months post EDIT-301 infusion
Secondary outcomes:
measure: Kinetics of HSPC engraftment
timeFrame: 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
measure: Kinetics of HSPC engraftment
timeFrame: 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.
measure: Incidence of transplant related mortality
timeFrame: 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
measure: Incidence of all-cause mortality
timeFrame: Screening through up to 24 months post EDIT-301 infusion
measure: Proportion of alleles per participant with intended genetic modification present in peripheral blood over time
timeFrame: EDIT-301 infusion (Day 0) through up to 24 months post EDIT-301 infusion
measure: Proportion of alleles per participant with intended genetic modification present in bone marrow cells over time
timeFrame: EDIT-301 infusion (Day 0) through up to 24 months post EDIT-301 infusion
measure: Change in the fetal hemoglobin (HbF) concentration compared to baseline overtime
timeFrame: Baseline through up to 24 months post EDIT-301 infusion
measure: Change in the total hemoglobin concentration compared to baseline overtime
timeFrame: Baseline through up to 24 months post EDIT-301 infusion
measure: Proportion of participants with hemoglobin concentration ≥ 9 g/dL
timeFrame: EDIT-301 infusion (Day 0) through 3, 6, 12 months up to 24 months post EDIT-301 infusion
measure: 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
timeFrame: 3 months post EDIT-301 infusion through up to 24 months post EDIT-301 infusion
measure: 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
timeFrame: 3 months through up to 24 months post EDIT-301 infusion
measure: Change in parameters of iron overload compared to baseline over time
timeFrame: Baseline through up to 24 months post EDIT-301 infusion
measure: Proportion of participants receiving iron chelation therapy over time
timeFrame: EDIT-301 infusion (Day 0) through up to 24 months post EDIT-301 infusion
Other outcomes:
Locations:
city: Oakland
country: United States
facility: University of California San Francisco
state: California
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: New York
country: United States
facility: Columbia University Medical Center - Department of Pediatrics
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Nashville
country: United States
facility: Tristar Medical Group Children's Specialists/Sarah Cannon Center for Blood Cancers
state: Tennessee
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre-University Health Network
state: Ontario
Study officials:
References: