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Gene Correction in Autologous CD34+ Hematopoietic Stem Cells (HbS to HbA) to Treat Severe Sickle Cell Disease (CEDAR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04819841
Recruitment Status : Recruiting
First Posted : March 29, 2021
Last Update Posted : June 29, 2022
Sponsor:
Information provided by (Responsible Party):
Graphite Bio, Inc.

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.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Genetic: GPH101 Drug Product Phase 1 Phase 2

Detailed Description:
Participants diagnosed with severe SCD will receive GPH101 via IV infusion following myeloablative conditioning in an autologous HSCT setting.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 15, 2021
Estimated Primary Completion Date : May 2026
Estimated Study Completion Date : May 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: GPH101 Drug Product
GPH101 Drug Product is a human autologous CRISPR-Cas9 edited and sickle mutation-corrected HSPC product.
Genetic: GPH101 Drug Product
GPH101 is administered via IV infusion following a myeloablative conditioning regimen




Primary Outcome Measures :
  1. Proportion of patients who reach neutrophil engraftment [ Time Frame: 42 days post-infusion ]
  2. Incidence rate of treatment-related mortality [ Time Frame: 100 days post-infusion ]
  3. Incidence rate of treatment-related mortality [ Time Frame: 12 months post-infusion ]
  4. Overall survival [ Time Frame: 24 months post-infusion ]
  5. Frequency and severity of AEs/SAEs [ Time Frame: 24 months post-infusion ]

Secondary Outcome Measures :
  1. Time to neutrophil engraftment [ Time Frame: through study completion, up to 24 months post-infusion ]
  2. Time to platelet engraftment [ Time Frame: through study completion, up to 24 months post-infusion ]
  3. Evaluation of gene correction levels in peripheral myeloid cells [ Time Frame: through study completion, up to 24 months post-infusion ]
  4. Evaluation of adult Hgb as a percentage of total Hgb [ Time Frame: through study completion, up to 24 months post-infusion ]
  5. Evaluation of HbS as a percentage of total Hgb [ Time Frame: through study completion, up to 24 months post-infusion ]
  6. Total Hgb without disease-indicated transfusion support [ Time Frame: through study completion, up to 24 months post-infusion ]
  7. 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 ]
  8. Proportion of participants with complete resolution of severe vaso-occlusive crises (sVOCs) [ Time Frame: over time, from 6 months to 18 months post-infusion ]
  9. Incidence rate of any sVOCs [ Time Frame: over time, from 6 months to study completion, up to 24 months post-infusion ]
  10. Proportion of participants achieving HbS <50% for at least 3 months [ Time Frame: through study completion, up to 24 months post-infusion ]
  11. Evaluation of globin chain expression compared to baseline [ Time Frame: through study completion, up to 24 months post-infusion ]


Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04819841


Contacts
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Contact: Allison Intondi, PhD 650-484-0886 clinicaltrials@graphitebio.com

Locations
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United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Emily Warner    205-996-1735    ewarner@uabmc.edu   
United States, California
Lucile Packard Children's Hospital Recruiting
Palo Alto, California, United States, 94304
Contact: Intake Team    650-723-0912    scgt_clinical_trials_office@lists.stanford.edu   
United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Katalin Kenney    314-273-5118    katalin@wustl.edu   
Sponsors and Collaborators
Graphite Bio, Inc.
Investigators
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Study Director: Ido Paz-Priel, MD Graphite Bio, Inc.
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Responsible Party: Graphite Bio, Inc.
ClinicalTrials.gov Identifier: NCT04819841    
Other Study ID Numbers: GPH101-001
First Posted: March 29, 2021    Key Record Dates
Last Update Posted: June 29, 2022
Last Verified: March 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Graphite Bio, Inc.:
sickle cell disease
sickle cell anemia
gene correction
gene therapy
CRISPR
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn