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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. Identifier: NCT04819841
Recruitment Status : Not yet recruiting
First Posted : March 29, 2021
Last Update Posted : June 11, 2021
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 the Correction of a Single Nucleotide Mutation (Adenosine --> Thymine [A-->T]) in Autologous CD34+ Hematopoietic Stem Cells to Convert HbS to HbA for Treating Severe Sickle Cell Disease
Estimated Study Start Date : August 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. Success of HSC engraftment [ Time Frame: 42 days post-infusion ]
    proportion of participants who reach neutrophil engraftment

  2. Transplant-related mortality [ Time Frame: 100 days post-infusion ]
  3. Transplant-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. Bone marrow HSPC or peripheral myeloid gene correction marking [ Time Frame: 24 months post-infusion ]
  2. Total HbS without disease-indicated transfusion support for ≥3 continuous months [ Time Frame: 24 months post-infusion ]
  3. Total HbA without disease-indicated transfusion support for ≥3 continuous months [ Time Frame: 24 months post-infusion ]
  4. Total Hgb without disease-indicated transfusion support for ≥3 continuous months [ Time Frame: 24 months post-infusion ]
  5. Change in annualized packed red blood cell (pRBC) transfusion requirements (volume and frequency) for SCD indications [ Time Frame: 6 and 24 months post-infusion ]
  6. Assessment of vaso-occlusive crises (VOC), Acute Chest Syndrome (ACS) episodes, and other SCD-related events compared to the 2 years prior to enrollment as documented by a visit to a medical facility [ Time Frame: 24 months post-infusion ]
  7. Change from baseline in transcranial Doppler (TCD) velocity in applicable participants with available TCD assessments [ Time Frame: 24 months post-infusion ]
  8. Change from baseline in SCD-indicated lab parameters, including but not limited to bilirubin, reticulocyte counts, erythropoietin, LDH, eGFR, haptoglobin, CRP [ Time Frame: 24 months post-infusion ]
  9. Evaluation of globin chain expression [ Time Frame: 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 months post-infusion ]
    hemoglobin fractions as percent of total

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

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 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

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 identifier (NCT number): NCT04819841

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Contact: Allison Intondi, PhD 650-484-0886

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United States, California
Lucile Packard Children's Hospital
Palo Alto, California, United States, 94304
Contact: Elisabeth Merkel, RN   
Sponsors and Collaborators
Graphite Bio, Inc.
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Study Director: Alexandria Petrusich Graphite Bio, Inc.
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Responsible Party: Graphite Bio, Inc. Identifier: NCT04819841    
Other Study ID Numbers: GPH101-001
First Posted: March 29, 2021    Key Record Dates
Last Update Posted: June 11, 2021
Last Verified: June 2021

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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
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hematologic Diseases
Genetic Diseases, Inborn