NCT06506461

Gene Editing For Sickle Cell Disease

St. Jude Autologous Genome Edited Stem Cells For Sickle Cell Disease-1

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 25 (estimated)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 24 Years
• Healthy volunteers: Not accepted

Summary

This study is being done to test the safety of a new treatment called gene editing in Sickle Cell Disease (SCD) patients and to see if a single dose of this genetically modified cellular product will increase the amount of a certain hemoglobin called fetal hemoglobin (HbF) and help reduce the symptoms of SCD. Primary Objective * To assess the safety of autologous infusion of clustered regularly interspaced palindromic repeats (CRISPR)/ CRISPR associated protein (Cas9)-edited CD34+ hematopoietic stem and progenitor cells (HSPCs) in patients with severe SCD. Secondary Objective * To assess the efficacy autologous infusion of CRISPR/Cas9 genome-edited CD34+ HSPCs into patients with severe SCD.

Detailed description

Participants will receive a daily subcutaneous (under the skin) dose of motixafortide for up to 3 consecutive days to mobilize their hematopoietic stem and progenitor cells (HSPCs) into peripheral blood. Participants who cannot tolerate motixafortide may receive a daily subcutaneous dose of plerixafor (Mozobil®) as an alternative for 3-5 consecutive days. About 2-4 hours after each dose of plerixafor/motixafortide is given, the collection of HSPCs will start via apheresis. The collected HSPCs will be sent to a lab to genetically modify them using CRISPR/Cas9. In the lab, the researchers will take the stem cells and purify them. The stem cells will then be mixed with the CRISPR-Cas9 gRNA ribonucleoprotein (RNP) complex to change (edit) the genes in the cells and produce the new gene edited cellular product. This gene edited drug product will be frozen until ready for infusion. Once the cellular product is ready, participants will be given Busulfan (a chemotherapy medicine) intravenously (IV) for 4 days. The thawed gene product will be given IV about 48 hours after the completion of the last dose of busulfan. Participants will be followed for 3 years on this study. After the three years, participants will be followed for 12 more years on a long-term follow-up study.

Conditions

• Sickle Cell Disease

Interventions

Type	Name	Description
DRUG	Plerixafor	Given Subcutaneous (under the skin)
DRUG	Busulfan	Given Intravenous (IV)
BIOLOGICAL	Gene-modified CD34+ cells	Given Intravenous (IV)
DRUG	Motixafortide	Given Subcutaneous (under the skin)

Timeline

• Start date: 2025-03-21
• Primary completion: 2029-12-01
• Completion: 2032-12-01
• First posted: 2024-07-17
• Last updated: 2025-11-14

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study