Sickle Cell DiseasePhase 1/2NCT04853576
A Study Evaluating the Safety and Efficacy of EDIT-301 in Participants With Severe Sickle Cell Disease (RUBY)
A Phase 1/2 study testing EDIT-301 in people with Sickle Cell Disease and Hemoglobinopathies, run by Editas Medicine, Inc. at 24 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 12 to 50 years
- Conditions the study is for
- Sickle Cell Disease, Hemoglobinopathies
- What is being tested?
- EDIT-301
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 24 sitesin 2 countries
- Study dates
- 4 May 2021to Aug 2025
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
24 sites in 2 countries.
24 sites in 2 countries
United States21 sites
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
Children's Hospital Colorado
Aurora, Colorado, 80045
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29425
Atrium Health
Charlotte, North Carolina, 28204
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
University Hospitals Rainbow Babies & Children's Hospital
Cleveland, Ohio, 44106
Cleveland Clinic
Cleveland, Ohio, 44195
Nationwide Children's Hospital
Columbus, Ohio, 43205
The James Cancer Hospital
Columbus, Ohio, 43210
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246
Cook Children's
Fort Worth, Texas, 76104
Hackensack University Medical Center
Hackensack, New Jersey, 07601
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Tristar Medical Group Children's Specialists/Sarah Cannon Center for Blood Cancers
Nashville, Tennessee, 37203
Smilow Cancer Hospital
New Haven, Connecticut, 06511
Columbia University Medical Center - Department of Pediatrics
New York, New York, 10032
Columbia University Medical Center
New York, New York, 10032
UCSF Benioff Children's Hospital
Oakland, California, 94609
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
Canada3 sites
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5
Ottawa Hospital Research Institute
Ottawa, Ontario, K1H 8L6
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
About this study
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
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).
Read the 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.
- Conditions
- Sickle Cell Disease, Hemoglobinopathies
- Being tested
- EDIT-301
- 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
- Medical subject headings
- Anemia, Sickle Cell, Hemoglobinopathies, Anemia, Anemia, Hemolytic, Congenital, Anemia, Hemolytic, Genetic Diseases, Inborn, Hematologic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EDIT-301Genetic
Also called renizgamglogene autogedtemcel, reni-cel
Administered by IV infusion after myeloablative conditioning with busulfan.
| Study group | Role | What they receive |
|---|---|---|
| EDIT-301 | Experimental | EDIT-301 (autologous gene edited (CD)34+ hematopoietic stem cells) will be administered as a one-time intravenous infusion. Receives: Genetic: EDIT-301 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of subjects achieving complete resolution of severe vaso-occlusive events (VOEs)
Measured: from Month 6 through Month 18 post EDIT-301 infusion
Secondary outcomes (17)
Proportion of subjects achieving complete resolution of VOEs
Measured: from Month 6 through Month 18 post EDIT-301 infusion
Proportion of subjects with 90% reduction in annualized rate of severe VOE compared to pre-treatment period
Measured: 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
Measured: starting from 6 months up to 2 years post EDIT-301 infusion
Proportion of subjects with 50% reduction in annualized rate of severe VOE compared to pre-treatment period
Measured: starting from 6 months up to 2 years post EDIT-301 infusion
Difference (pre-treatment vs. post-treatment) in annualized rates of severe VOEs
Measured: 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
Measured: starting from 6 months up to 2 years post EDIT-301 infusion
Proportion of subjects with sustained HbF ≥ 20% (HbF/Hb) compared with baseline
Measured: starting from 6 months up to 2 years post EDIT-301 infusion
Proportion of subjects with mean HbF ≥ 30% (HbF/Hb) compared with baseline
Measured: 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
Measured: 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
Measured: 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
Measured: starting from 6 months up to 2 years post EDIT-301 infusion
Change from baseline in HbF concentration (g/dL)
Measured: up to 2 years post EDIT-301 infusion
Change from baseline in total Hb concentration (g/dL)
Measured: up to 2 years post EDIT-301 infusion
Change from baseline in markers of hemolysis (absolute reticulocyte count, indirect bilirubin, lactate dehydrogenase, haptoglobin)
Measured: 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)
Measured: 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)
Measured: up to 24 months after EDIT-301 infusion
Frequency and severity of adverse events (AEs)
Measured: up to 24 months post EDIT-301 infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2021
- Study start4 May 2021
- Primary completionAug 2025 (estimated)
- Study completionAug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Editas Medicine, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04853576
- Sponsor's protocol ID
- EM-SCD-301-001
- Status last verified
- Jan 2025
- First submitted
- 16 Apr 2021
- Last updated
- 31 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hanna R, Frangoul H, Pineiro L, McKinney C, Mapara M, Dalal J, Rangarajan HG, Atkins H, Sharma A, Chang KH, Jaskolka MC, Kim K, Yu Q, Mei B, Afonja O, Walters MC; RUBY Investigators. CRISPR-Cas12a Gene Editing of HBG1 and HBG2 Promoters to Treat Sickle Cell Disease. N Engl J Med. 2026 Apr 2;394(13):1281-1291. doi: 10.1056/NEJMoa2415550.
PubMed 41931047
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04853576
- Acronym / sponsor ID
- EM-SCD-301-001
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Editas Medicine, Inc.Industry (pharma, biotech, devices)
- Study start
- 4 May 2021 (actual)
- Primary completion
- Aug 2025 (estimated)
- Study completion
- Aug 2025 (estimated)
- First posted
- 21 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| EDIT-301 | Experimental | Genetic: EDIT-301EDIT-301 (autologous gene edited (CD)34+ hematopoietic stem cells) will be administered as a one-time intravenous infusion. |
Who may qualify
- Ages
- 12 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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 (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EDIT-301Also: renizgamglogene autogedtemcel, reni-celAdministered by IV infusion after myeloablative conditioning with busulfan. | Genetic | EDIT-301 |
Primary outcome
Proportion of subjects achieving complete resolution of severe vaso-occlusive events (VOEs)
Time frame: from Month 6 through Month 18 post EDIT-301 infusion
17 secondary outcomes
Proportion of subjects achieving complete resolution of VOEs
Time frame: from Month 6 through Month 18 post EDIT-301 infusion
Proportion of subjects with 90% reduction in annualized rate of severe VOE compared to pre-treatment period
Time frame: 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
Time frame: starting from 6 months up to 2 years post EDIT-301 infusion
Proportion of subjects with 50% reduction in annualized rate of severe VOE compared to pre-treatment period
Time frame: starting from 6 months up to 2 years post EDIT-301 infusion
Difference (pre-treatment vs. post-treatment) in annualized rates of severe VOEs
Time frame: 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
Time frame: starting from 6 months up to 2 years post EDIT-301 infusion
Proportion of subjects with sustained HbF ≥ 20% (HbF/Hb) compared with baseline
Time frame: starting from 6 months up to 2 years post EDIT-301 infusion
Proportion of subjects with mean HbF ≥ 30% (HbF/Hb) compared with baseline
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: starting from 6 months up to 2 years post EDIT-301 infusion
Change from baseline in HbF concentration (g/dL)
Time frame: up to 2 years post EDIT-301 infusion
Change from baseline in total Hb concentration (g/dL)
Time frame: up to 2 years post EDIT-301 infusion
Change from baseline in markers of hemolysis (absolute reticulocyte count, indirect bilirubin, lactate dehydrogenase, haptoglobin)
Time frame: 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)
Time frame: 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)
Time frame: up to 24 months after EDIT-301 infusion
Frequency and severity of adverse events (AEs)
Time frame: up to 24 months post EDIT-301 infusion
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2025.
- Derived from this study: PubMed 41931047Hanna R, Frangoul H, Pineiro L, McKinney C, Mapara M, Dalal J, Rangarajan HG, Atkins H, Sharma A, Chang KH, Jaskolka MC, Kim K, Yu Q, Mei B, Afonja O, Walters MC; RUBY Investigators. CRISPR-Cas12a Gene Editing of HBG1 and HBG2 Promoters to Treat Sickle Cell Disease. N Engl J Med. 2026 Apr 2;394(13):1281-1291. doi: 10.1056/NEJMoa2415550.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
24 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing EDIT-301 in people with Sickle Cell Disease and Hemoglobinopathies, run by Editas Medicine, Inc. at 24 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 31 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of subjects achieving complete resolution of severe vaso-occlusive events (VOEs) (time frame: from Month 6 through Month 18 post EDIT-301 infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04853576, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2025.