Clinical trial NCT04853576: A Study Evaluating the Safety and Efficacy of EDIT-301 in Participants With Severe Sickle Cell Disease (RUBY)
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Sickle Cell Disease
Hemoglobinopathies
Keywords: Anemia
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Genetic Diseases, Inborn
Cell Disorders, Sickle
HbS Disease
Sickling Disorder Due to Hemoglobin S
Hematologic Diseases
Lead sponsor: Editas Medicine, Inc.
Sponsor class: INDUSTRY
First posted: 2021-04-21
Enrollment: 45
Sex: ALL
Minimum age (years): 12
Maximum age (years): 50
Standard ages: CHILD
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 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.

Eligibility criteria: Key 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

Key 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
* Clinically significant and active bacterial, viral, fungal, or parasitic infection

Other protocol defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Proportion of subjects achieving complete resolution of severe vaso-occlusive events (VOEs)
timeFrame: from Month 6 through Month 18 post EDIT-301 infusion
Secondary outcomes:
measure: Proportion of subjects achieving complete resolution of VOEs
timeFrame: from Month 6 through Month 18 post EDIT-301 infusion
measure: Proportion of subjects with 90% reduction in annualized rate of severe VOE compared to pre-treatment period
timeFrame: starting from 6 months up to 2 years post EDIT-301 infusion
measure: Proportion of subjects with 75% reduction in annualized rate of severe VOE compared to pre-treatment period
timeFrame: starting from 6 months up to 2 years post EDIT-301 infusion
measure: Proportion of subjects with 50% reduction in annualized rate of severe VOE compared to pre-treatment period
timeFrame: starting from 6 months up to 2 years post EDIT-301 infusion
measure: Difference (pre-treatment vs. post-treatment) in annualized rates of severe VOEs
timeFrame: starting from 6 months up to 2 years post EDIT-301 infusion
measure: Difference (pre-treatment vs. post-treatment) in annualized rate of hospitalization for severe VOEs
timeFrame: starting from 6 months up to 2 years post EDIT-301 infusion
measure: Proportion of subjects with sustained HbF ≥ 20% (HbF/Hb) compared with baseline
timeFrame: starting from 6 months up to 2 years post EDIT-301 infusion
measure: Proportion of subjects with mean HbF ≥ 30% (HbF/Hb) compared with baseline
timeFrame: starting from 6 months up to 2 years post EDIT-301 infusion
measure: Proportion of subjects with mean total Hb ≥ 10 g/dL compared with baseline
timeFrame: starting from 6 months up to 2 years post EDIT-301 infusion
measure: Proportion of subjects with mean total Hb increase from baseline of ≥ 2 g/dL
timeFrame: starting from 6 months up to 2 years post EDIT-301 infusion
measure: Difference (pre-treatment versus post-treatment) in annualized number of units of pRBC transfused for SCD-related indications
timeFrame: starting from 6 months up to 2 years post EDIT-301 infusion
measure: Change from baseline in HbF concentration (g/dL)
timeFrame: up to 2 years post EDIT-301 infusion
measure: Change from baseline in total Hb concentration (g/dL)
timeFrame: up to 2 years post EDIT-301 infusion
measure: Change from baseline in markers of hemolysis (absolute reticulocyte count, indirect bilirubin, lactate dehydrogenase, haptoglobin)
timeFrame: up to 2 years post EDIT-301 infusion
measure: 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)
timeFrame: up to 24 months after EDIT-301 infusion
measure: 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)
timeFrame: up to 24 months after EDIT-301 infusion
measure: Frequency and severity of adverse events (AEs)
timeFrame: up to 24 months post EDIT-301 infusion
Other outcomes:
Locations:
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: New Haven
country: United States
facility: Smilow Cancer Hospital
state: Connecticut
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
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: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Atrium Health
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Rainbow Babies & Children's Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: The James Cancer Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Tristar Medical Group Children's Specialists/Sarah Cannon Center for Blood Cancers
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's
state: Texas
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montréal
country: Canada
facility: Centre Hospitalier Universitaire Sainte-Justine
state: Quebec
Study officials:
References: