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

• ClinicalTrials.gov Identifier: NCT04819841
• Recruitment Status: Terminated
• First Posted: March 29, 2021
• Last Update Posted: May 9, 2023
• Sponsor: Graphite Bio, Inc.
• Information provided by (Responsible Party): Graphite Bio, Inc.

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.

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 6 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
• Actual Primary Completion Date: April 6, 2023
• Actual Study Completion Date: April 6, 2023

Arms and Interventions

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

Outcome Measures

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 ]

Eligibility Criteria

• 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

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

United States, California

Lucile Packard Children's Hospital

Palo Alto, California, United States, 94304

United States, Missouri

Washington University

Saint Louis, Missouri, United States, 63110

Sponsors and Collaborators

Graphite Bio, Inc.

Investigators

• Study Director: Weston Miller, MD; Graphite Bio, Inc.

More Information

• Responsible Party: Graphite Bio, Inc.
• ClinicalTrials.gov Identifier: NCT04819841
• Other Study ID Numbers: GPH101-001
• First Posted: March 29, 2021
• Last Update Posted: May 9, 2023
• Last Verified: May 2023

• 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:

Anemia, Sickle Cell; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn