A Phase 1/2 Study to Evaluate the Safety and Efficacy of a Single Dose of Autologous Clustered Regularly Interspaced Short Palindromic Repeats Gene-edited CD34+ Human Hematopoietic Stem and Progenitor Cells (EDIT-301) in Subjects With Severe Sickle Cell Disease

Editas Medicine, Inc.24 sites in 2 countries45 target enrollmentMay 4, 2021

ConditionsSickle Cell Disease Hemoglobinopathies

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Sickle Cell Disease
Sponsor: Editas Medicine, Inc.
Enrollment: 45
Locations: 24
Primary Endpoint: Proportion of subjects achieving complete resolution of severe vaso-occlusive events (VOEs)
Status: Active, not recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

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 sickle cell disease (SCD).

Detailed Description

This is a Phase 1/2 single-arm, open-label, multicenter study evaluating the safety and efficacy of a single unit dose of EDIT-301 for autologous hematopoietic stem cell transplant (HSCT) in subjects with severe SCD. Planned study subjects will be comprised of male and female adult and adolescent subjects with severe SCD, from 12 to 50 years of age, inclusive.

Registry

clinicaltrials.gov

Start Date

May 4, 2021

End Date

August 2025

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Editas Medicine, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Diagnosis of severe sickle cell disease as defined by:
•Documented SCD genotype (βS/βS, βS/β0, βS/β+, or others) and
•History of at least two severe vaso-occlusive events per year requiring medical attention despite hydroxyurea or other supportive care measures in the two year-period prior to provision of informed consent or assent, as applicable
•Karnofsky (for subjects \>16 years of age) or Lansky (for subjects ≤ 16 years of age) Performance Status ≥ 80%
•Normal transcranial doppler velocity in subjects 16 years of age or younger

Exclusion Criteria

•Available 10/10 HLA-matched related donor
•Prior HSCT or contraindications to autologous HSCT
•Any contraindications to the use of plerixafor during the mobilization of hematopoietic stem cells (HSCs) and any contraindications to the use of busulfan and any other medicinal products required during the myeloablative conditioning, including hypersensitivity to the active substances or to any of the excipients
•Unable to receive red blood cell (RBC) transfusion for any reason
•Unable or unwilling to comply with standard of care changes in background medical treatment in preparation of, during, or following HSCT, including and not limited to discontinuation of hydroxyurea, voxelotor, crizanlizumab, or L-glutamine
•Any history of severe cerebral vasculopathy
•Inadequate end organ function
•Advanced liver disease
•Any prior or current malignancy or immunodeficiency disorder
•Immediate family member with a known or suspected Familial Cancer Syndrome

Outcomes

Primary Outcomes

Proportion of subjects achieving complete resolution of severe vaso-occlusive events (VOEs)

Time Frame: from Month 6 through Month 18 post EDIT-301 infusion

Secondary Outcomes

Proportion of subjects with 90% reduction in annualized rate of severe VOE compared to pre-treatment period(starting from 6 months up to 2 years post EDIT-301 infusion)
Proportion of subjects with 75% reduction in annualized rate of severe VOE compared to pre-treatment period(starting from 6 months up to 2 years post EDIT-301 infusion)
Proportion of subjects achieving complete resolution of VOEs(from Month 6 through Month 18 post EDIT-301 infusion)
Proportion of subjects with 50% reduction in annualized rate of severe VOE compared to pre-treatment period(starting from 6 months up to 2 years post EDIT-301 infusion)
Difference (pre-treatment vs. post-treatment) in annualized rates of severe VOEs(starting from 6 months up to 2 years post EDIT-301 infusion)
Difference (pre-treatment vs. post-treatment) in annualized rate of hospitalization for severe VOEs(starting from 6 months up to 2 years post EDIT-301 infusion)
Proportion of subjects with sustained HbF ≥ 20% (HbF/Hb) compared with baseline(starting from 6 months up to 2 years post EDIT-301 infusion)
Proportion of subjects with mean HbF ≥ 30% (HbF/Hb) compared with baseline(starting from 6 months up to 2 years post EDIT-301 infusion)
Proportion of subjects with mean total Hb ≥ 10 g/dL compared with baseline(starting from 6 months up to 2 years post EDIT-301 infusion)
Proportion of subjects with mean total Hb increase from baseline of ≥ 2 g/dL(starting from 6 months up to 2 years post EDIT-301 infusion)
Difference (pre-treatment versus post-treatment) in annualized number of units of pRBC transfused for SCD-related indications(starting from 6 months up to 2 years post EDIT-301 infusion)
Change from baseline in HbF concentration (g/dL)(up to 2 years post EDIT-301 infusion)
Change from baseline in total Hb concentration (g/dL)(up to 2 years post EDIT-301 infusion)
Change from baseline in markers of hemolysis (absolute reticulocyte count, indirect bilirubin, lactate dehydrogenase, haptoglobin)(up to 2 years post EDIT-301 infusion)
Time to neutrophil engraftment (the first day in which 3 consecutive absolute neutrophil count (ANC) ≥ 0.5 x 109/L laboratory values obtained on different days)(up to 24 months after EDIT-301 infusion)
Time to platelet engraftment (the first day in which 3 consecutive platelets ≥ 50 x 109/L laboratory values obtained for at least 7 days following the last platelet transfusion and 10 days following any administration of thrombopoietin (TPO) mimetics)(up to 24 months after EDIT-301 infusion)
Frequency and severity of adverse events (AEs)(up to 24 months post EDIT-301 infusion)