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

Sponsor

Graphite Bio, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04819841

Collaborator

(none)

Enrollment

Locations

Arm

53.5

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

Anticipated 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 :

Nov 15, 2021

Anticipated Primary Completion Date :

May 1, 2026

Anticipated Study Completion Date :

May 1, 2026

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

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

Proportion of patients who reach neutrophil engraftment [42 days post-infusion]
Incidence rate of treatment-related mortality [100 days post-infusion]
Incidence rate of treatment-related mortality [12 months post-infusion]
Overall survival [24 months post-infusion]
Frequency and severity of AEs/SAEs [24 months post-infusion]

Secondary Outcome Measures

Time to neutrophil engraftment [through study completion, up to 24 months post-infusion]
Time to platelet engraftment [through study completion, up to 24 months post-infusion]
Evaluation of gene correction levels in peripheral myeloid cells [through study completion, up to 24 months post-infusion]
Evaluation of adult Hgb as a percentage of total Hgb [through study completion, up to 24 months post-infusion]
Evaluation of HbS as a percentage of total Hgb [through study completion, up to 24 months post-infusion]
Total Hgb without disease-indicated transfusion support [through study completion, up to 24 months post-infusion]
Change in annualized packed red blood cell (pRBC) transfusion requirements (volume and frequency) for SCD indications [through study completion, up to 24 months post-infusion]
Proportion of participants with complete resolution of severe vaso-occlusive crises (sVOCs) [over time, from 6 months to 18 months post-infusion]
Incidence rate of any sVOCs [over time, from 6 months to study completion, up to 24 months post-infusion]
Proportion of participants achieving HbS <50% for at least 3 months [through study completion, up to 24 months post-infusion]
Evaluation of globin chain expression compared to baseline [through study completion, up to 24 months post-infusion]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 40 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Lucile Packard Children's Hospital	Palo Alto	California	United States	94304
3	Washington University	Saint Louis	Missouri	United States	63110