Gene Editing For Sickle Cell Disease

NCT06506461 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: SAGES1U01HL163983
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Sickle Cell Disease

Keywords

Plerixafor; Autologous; CD34+ cells; Apheresis; Conditioning; Busulfan; Gene Editing

Outcome Measures

Primary Outcomes (5)

• Incidence of neutrophil engraftment by day +42 after infusion of the CRISPR/Cas9-edited CD34+ HSPCs.

  Upon completion of the trial, summary statistics will be computed for the time to neutrophil engraftment.

  Within 42 days of the cellular product infusion

• Incidence of platelet engraftment by day +60 after infusion of the CRISPR/Cas9-edited CD34+ HSPCs.

  Upon completion of the trial, summary statistics will be computed for the time to platelet engraftment.

  Within 60 days of the cellular product infusion

• Sustenance of multi-lineage engraftment and polyclonal hematopoiesis as measured by counts of different clones of myeloid cells, T cells, B cells, and NK cells at 1 year after infusion of the CRISPR/Cas9-edited CD34+ HSPCs.

  Sustenance of multi-lineage engraftment will be described using descriptive statistics.

  Within 1 year of the cellular product infusion

• Frequency of off-target editing after infusion of the CRISPR/Cas9-edited CD34+ HSPCs.

  Frequency of off-target editing will be described using descriptive statistics.

  Within 3 years of the cellular product infusion

• Occurrence of secondary graft failure, clonal hematopoiesis, MDS, or AML

  Occurrence will be described using descriptive statistics.

  Within 3 years of the cellular product infusion

Secondary Outcomes (4)

• Estimate the change in the annualized rate of SCD-related vaso-occlusive events (such as pain crises and acute chest syndrome events), starting at 3 months after the infusion of autologous CRISPR/Cas9-edited CD34+ HSPCs.

  From 3 months post the cellular product infusion to 3 years post infusion

• Compare the change from baseline in the total blood hemoglobin concentration.

  From time of screening to 3 years post infusion

• Compare the change from baseline in the fraction of red blood cells (RBCs) containing HbF.

  From time of screening to 3 years post infusion

• Change in incidence of packed RBC transfusions.

  Within 1 year prior to infusion and within 3 months to 1 year post infusion

Study Arms (1)

Autologous, genetically modified CD34+ HSPCs Treatment

EXPERIMENTAL

All eligible participants receive intervention as described in the Detailed Description with the following: motixafortide, plerixafor, busulfan, and autologous, gene-modified CD34+ cells

Drug: Plerixafor; Drug: Busulfan; Biological: Gene-modified CD34+ cells; Drug: Motixafortide

Interventions

Plerixafor DRUG

Given Subcutaneous (under the skin)

Also known as: Mozobil®

Autologous, genetically modified CD34+ HSPCs Treatment

Busulfan DRUG

Given Intravenous (IV)

Also known as: Myleran®, Busulfex

Autologous, genetically modified CD34+ HSPCs Treatment

Gene-modified CD34+ cells BIOLOGICAL

Given Intravenous (IV)

Autologous, genetically modified CD34+ HSPCs Treatment

Motixafortide DRUG

Given Subcutaneous (under the skin)

Also known as: Aphexda

Autologous, genetically modified CD34+ HSPCs Treatment

Eligibility Criteria

• Age: 18 Years - 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age ≥18 years and ≤24.9 years.
• Patients with SCD (Hb SS, Hb SB0 and Hb SB+ genotype) who have experienced EITHER (a) 2 or more SCD-related vaso-occlusive events (acute pain events, acute chest syndrome, priapism and splenic sequestration) per year in the 2-year period before screening, OR (b) administration of regular red blood cell (RBC) transfusions (≥8 transfusions in the 12 months preceding enrollment) EXCEPT if the RBC transfusions are being administered for primary or secondary stroke prevention and, in the opinion of the treating hematologist, cannot be safely discontinued after infusion of the gene modified drug product.
• Failure, intolerance, or refusal of hydroxyurea therapy.
• Patients must be eligible for autologous stem cell transplant as per investigator's judgment.
• Females of childbearing potential (i.e., those who are post-menarchal with an intact uterus and at least 1 ovary, and those who are less than 1 year postmenopausal) must agree to use acceptable method(s) of contraception from start of mobilization through at least 6 months post-infusion.
• Males must agree to use effective contraception from start of mobilization through at least 6 months post-infusion.
• Patients should be willing to participate in an additional long-term follow-up study after completion of this trial.

You may not qualify if:

• Availability of an human leukocyte antigen (HLA)-matched sibling who is willing and able to donate an appropriate graft for hematopoietic cell transplantation (HCT).
• Karnofsky or Lansky performance score \< 80.
• Pregnant, as confirmed by positive serum or urine pregnancy test within 14 days before enrollment (if female).
• Breastfeeding.
• Uncontrolled (undergoing appropriate treatment and with progression of clinical symptoms) or clinically significant bacterial, viral, or fungal infections within 1 month before enrollment.
• Patients with confirmed Hepatitis B or Hepatitis C infections.
• Patients with confirmed seropositivity or positive nucleic acid amplification test (NAAT) for human immunodeficiency virus (HIV) or human T-cell lymphotropic virus (HTLV).
• Patients with a history of stroke.
• Serum conjugated (direct) bilirubin \> 2× the upper limit of normal for age, or serum alanine transaminase (ALT) \> 3× the upper limit of normal for age as per the local laboratory. Participants with hyperbilirubinemia or elevated aspartate aminotransferase (AST) as the result of hyperhemolysis, or with a severe drop in hemoglobin post blood transfusion, are not excluded as long as these values downtrend and return to acceptable limits subsequently.
• Left ventricular shortening fraction \< 25% or ejection fraction \< 45% by echocardiogram.
• Estimated creatinine clearance less than 60 mL/min/1.73m\^2.
• Diffusion capacity of carbon monoxide (DLCO) \< 50% (adjusted for hemoglobin) OR baseline oxygen saturation \< 85% in patients unable to perform pulmonary function tests.
• Prior HCT or gene therapy.
• Known hepatic cirrhosis, bridging hepatic fibrosis, or active hepatitis. Appropriate ultrasound or magnetic resonance (MR) imaging may be used to define the presence and degree of cirrhosis. Liver biopsy may be performed at the discretion of the attending physician or principal investigator if there are concerns regarding the presence of severe hepatic fibrosis or cirrhosis such that participation in this trial will not be in the patient's best interest.
• Active known malignancy, myelodysplasia, abnormal cytogenetics, or immunodeficiency.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

plerixafor; Busulfan

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Akshay Sharma, MBBS, MSc

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Akshay Sharma, MBBS, MSc

CONTACT

888-226-4343; referralinfo@stjude.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients with severe sickle cell disease (SCD)

Study Record Dates

• First Submitted: June 14, 2024
• First Posted: July 17, 2024
• Study Start: March 21, 2025
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2032
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available at the time of article publication.
• Access Criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

Locations

US (1)