Back to resultsGene Correction in Autologous CD34+ Hematopoietic Stem Cells (HbS to HbA) to Treat Severe Sickle Cell Disease (CEDAR)
Primary Purpose
Sickle Cell Disease
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
GPH101 Drug Product
Sponsored by
About this trial
This is an interventional treatment trial for Sickle Cell Disease focused on measuring sickle cell disease, sickle cell anemia, gene correction, gene therapy, CRISPR
Eligibility Criteria
Inclusion Criteria:
- ≥12 to ≤ 40 years
- Severe disease, as defined by having experienced at least one of the following SCD-related events despite appropriate supportive care measures:
- recurrent severe VOC (≥ 4 episodes in the preceding 2 years)
- ACS (≥ 2 episodes in the prior 2 years with at least one episode in the past year)
- Lansky/Karnofsky performance status of ≥ 80
Exclusion Criteria:
- Available 10/10 HLA-matched sibling donor
- Prior HSCT or gene therapy
- Prior or current malignancy or myeloproliferative or a significant coagulation or immunodeficiency disorder
- Clinically significant and active bacterial, viral, fungal or parasitic infection
- Pregnancy or breastfeeding in a postpartum female
- Presence of a chromosomal abnormality/mutation that may put the participant at an increased risk for MDS or AML per investigator's judgment
Sites / Locations
- University of Alabama at Birmingham
- Lucile Packard Children's Hospital
- Washington University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
GPH101 Drug Product
Arm Description
GPH101 Drug Product is a human autologous CRISPR-Cas9 edited and sickle mutation-corrected HSPC product.
Outcomes
Primary Outcome Measures
Proportion of patients who reach neutrophil engraftment
Incidence rate of treatment-related mortality
Incidence rate of treatment-related mortality
Overall survival
Frequency and severity of AEs/SAEs
Secondary Outcome Measures
Time to neutrophil engraftment
Time to platelet engraftment
Evaluation of gene correction levels in peripheral myeloid cells
Evaluation of adult Hgb as a percentage of total Hgb
Evaluation of HbS as a percentage of total Hgb
Total Hgb without disease-indicated transfusion support
Change in annualized packed red blood cell (pRBC) transfusion requirements (volume and frequency) for SCD indications
Proportion of participants with complete resolution of severe vaso-occlusive crises (sVOCs)
Incidence rate of any sVOCs
Proportion of participants achieving HbS <50% for at least 3 months
Evaluation of globin chain expression compared to baseline
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04819841
Brief Title
Gene Correction in Autologous CD34+ Hematopoietic Stem Cells (HbS to HbA) to Treat Severe Sickle Cell Disease
Acronym
CEDAR
Official Title
A Phase I/II Study of GPH101 in Autologous CD34+ Hematopoietic Stem Cells to Convert HbS to HbA for Treating Severe Sickle Cell Disease
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Terminated
Why Stopped
Study Stopped at Sponsor Discretion
Study Start Date
November 15, 2021 (Actual)
Primary Completion Date
April 6, 2023 (Actual)
Study Completion Date
April 6, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Graphite Bio, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This study is a first-in-human, single-arm, open-label Phase I/II study of GPH101 in approximately 15 participants, diagnosed with severe Sickle Cell Disease. The primary objective is to evaluate safety of the treatment in this patient population, as well as preliminary efficacy and pharmacodynamic data.
Detailed Description
Participants diagnosed with severe SCD will receive GPH101 via IV infusion following myeloablative conditioning in an autologous HSCT setting.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease
Keywords
sickle cell disease, sickle cell anemia, gene correction, gene therapy, CRISPR
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
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GPH101 Drug Product
Arm Type
Experimental
Arm Description
GPH101 Drug Product is a human autologous CRISPR-Cas9 edited and sickle mutation-corrected HSPC product.
Intervention Type
Genetic
Intervention Name(s)
GPH101 Drug Product
Intervention Description
GPH101 is administered via IV infusion following a myeloablative conditioning regimen
Primary Outcome Measure Information:
Title
Proportion of patients who reach neutrophil engraftment
Time Frame
42 days post-infusion
Title
Incidence rate of treatment-related mortality
Time Frame
100 days post-infusion
Title
Incidence rate of treatment-related mortality
Time Frame
12 months post-infusion
Title
Overall survival
Time Frame
24 months post-infusion
Title
Frequency and severity of AEs/SAEs
Time Frame
24 months post-infusion
Secondary Outcome Measure Information:
Title
Time to neutrophil engraftment
Time Frame
through study completion, up to 24 months post-infusion
Title
Time to platelet engraftment
Time Frame
through study completion, up to 24 months post-infusion
Title
Evaluation of gene correction levels in peripheral myeloid cells
Time Frame
through study completion, up to 24 months post-infusion
Title
Evaluation of adult Hgb as a percentage of total Hgb
Time Frame
through study completion, up to 24 months post-infusion
Title
Evaluation of HbS as a percentage of total Hgb
Time Frame
through study completion, up to 24 months post-infusion
Title
Total Hgb without disease-indicated transfusion support
Time Frame
through study completion, up to 24 months post-infusion
Title
Change in annualized packed red blood cell (pRBC) transfusion requirements (volume and frequency) for SCD indications
Time Frame
through study completion, up to 24 months post-infusion
Title
Proportion of participants with complete resolution of severe vaso-occlusive crises (sVOCs)
Time Frame
over time, from 6 months to 18 months post-infusion
Title
Incidence rate of any sVOCs
Time Frame
over time, from 6 months to study completion, up to 24 months post-infusion
Title
Proportion of participants achieving HbS <50% for at least 3 months
Time Frame
through study completion, up to 24 months post-infusion
Title
Evaluation of globin chain expression compared to baseline
Time Frame
through study completion, up to 24 months post-infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
≥12 to ≤ 40 years
Severe disease, as defined by having experienced at least one of the following SCD-related events despite appropriate supportive care measures:
recurrent severe VOC (≥ 4 episodes in the preceding 2 years)
ACS (≥ 2 episodes in the prior 2 years with at least one episode in the past year)
Lansky/Karnofsky performance status of ≥ 80
Exclusion Criteria:
Available 10/10 HLA-matched sibling donor
Prior HSCT or gene therapy
Prior or current malignancy or myeloproliferative or a significant coagulation or immunodeficiency disorder
Clinically significant and active bacterial, viral, fungal or parasitic infection
Pregnancy or breastfeeding in a postpartum female
Presence of a chromosomal abnormality/mutation that may put the participant at an increased risk for MDS or AML per investigator's judgment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Weston Miller, MD
Organizational Affiliation
Graphite Bio, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Lucile Packard Children's Hospital
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Gene Correction in Autologous CD34+ Hematopoietic Stem Cells (HbS to HbA) to Treat Severe Sickle Cell Disease
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