Safety and Efficacy of Gene Therapy of the Sickle Cell Disease by Transplantation of an Autologous CD34+ Enriched Cell Fraction That Contains CD34+ Cells Transduced ex Vivo With the GLOBE1 Lentiviral Vector Expressing the βAS3 Globin Gene in Patients With Sickle Cell Disease (DREPAGLOBE)

NCT03964792 | Completed Phase 1 DMC

• 1 other identifier: P17006J
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the Safety and Efficacy of Gene Therapy of the Sickle Cell disease by Transplantation of an Autologous CD34+ enriched cell fraction that contains CD34+ cells transduced ex vivo with the GLOBE1 lentiviral vector expressing the βAS3 globin gene (GLOBE1 βAS3 Modified Autologous CD34+ Cells) in Patients with Sickle Cell Disease (SCD)

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (5)

• Incidence of transplant related mortality

  To evaluate the procedure safety

  up to 100 days post treatment

• Incidence of the need for rescue autologous bone marrow transplant

  To evaluate the procedure safety

  up to 100 days post treatment

• Frequency and severity of AEs post transplant transplant

  Based on the United States national Cancer Institute Common Terminology Criteria for Adverse Events v4.03 To evaluate the procedure safety

  6 months post-transplant

• Incidence of vector-derived Replication competent lentivirus (RCL)

  To evaluate the procedure safety

  6 months post-transplant

• Incidence of clinically detectable malignancy and/or abnormal clonal dominance assessed as related to study treatment

  To evaluate the procedure safety.It will be evaluated by vector insertion site analysis (VISA.

  6 months post-transplant

Secondary Outcomes (7)

• Concentration of neutrophil

  6 months post-transplant

• Concentration of platelet

  6 months post-transplant

• Percentage HbAS3

  6 months post-transplant

• Frequency and severity of adverse events

  24 months post-transplant

• Absence of RCL (Replication competent lentivirus)

  24 months post-transplant

Study Arms (1)

DREPAGLOBE drug product

EXPERIMENTAL

The DREPAGLOBE is a genetically modified cell therapy product that consists of autologous human CD34+ hematopoietic stem and progenitor cells (HSPCs) that are enriched in CD34+ cells which have been transduced ex vivo with the lentiviral vector, GLOBE1, expressing an anti-sickling β-globin protein (AS3) containing three amino acid substitutions in the wild-type β-globin gene.

Genetic: DREPAGLOBE drug product

Interventions

DREPAGLOBE drug product GENETIC

Each patient will receive a single IV infusion of DREPAGLOBE drug product

DREPAGLOBE drug product

Eligibility Criteria

• Age: 12 Years - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \- Age 12-20 years
• Diagnosis of HbSS or S-beta zero thalassemia by Hb electrophoresis or genetic analysis.
• Clinical history or ongoing evidence of severe sickle cell anemia with one OR more of the following clinical complications demonstrating disease severity:
• At least 3 vaso occlusive crises requiring hospitalization, under hydroxyurea or transfusion, within 2 years prior to enrollment
• One severe acute chest syndrome (ACS) hospitalized in intensive care unit
• At least 2 episodes of ACS within the prior 3 years), including one under HU.
• Acute priapism (at least 2 episodes \> 3h in the preceding year or in the year prior to the start of a regular transfusion program), OR stuttering priapism ≥ 1 by week under sickle cell treatment (HU, transfusion or phlebotomy).
• Cerebral vasculopathy confirmed by MRA (magnetic resonance angiography) without Moya-moya
• Presence of sickle cell cardiomyopathy documented by Doppler echocardiography (left ventricular ejection fraction (LVEF) \<55% AND tricuspid regurgitation velocity \>2.5m/s on cardiac echocardiograph),
• Tricuspid regurgitation velocity \>2.8m/s on cardiac echocardiograph without pulmonary hypertension confirmed by right heart catheterization (mPAP\<25mmHg)
• Failed hydroxyurea (HU) therapy, were unable to tolerate HU therapy, or, if 18 years of age or older, have actively made the choice to not take the recommended daily HU regimen. Inadequate clinical response to HU, defined as any one of the following outcomes, while on HU for at least 3 months: 2 or more acute sickle pain crises requiring hospitalization, no rise in Hb \>1.5 gm/dl from pre-HU baseline or requires transfusion to maintain Hb \> 6.0 gm/dL, had an episode of ACS despite adequate supportive care measures.
• Karnovsky/Lansky performance score ≥ 60%
• Sexually active patients must be willing to use an acceptable method of double-barrier contraception for at least 12 months post-infusion (beyond 12 months at the discretion of the investigator)

You may not qualify if:

• Chromosomal (karyotyping) or molecular anomalies (detected by NGS) ( ie 7 chromosomal monosomy)
• Existence of a matched sibling donor
• Patients who have started new treatment for SCD within 6months of enrollment
• Hematologic evaluation: Leukopenia (WBC \< 3000 µL) ( en cours) or neutropenia (ANC \< 1000 µL) or thrombocytopenia (platelet count \< 100,000 µL) (not due to an erythropheresis procedure)
• PT/INR or PTT \> 1.5 times upper limit of normal (ULN) or clinically significant bleeding disorder
• Evaluations within 6 months prior to screening visit:
• ALT or AST \> 3 times ULN
• Liver Cirrhosis suspicion on echography, CT scan or MRI AND confirmed by histology
• Cardiac evaluation: LVEF \< 40% by cardiac echocardiogram or by MUGA scan
• Stroke with significant CNS sequelae i.e., Rankin \> 2
• Lung interstitial infiltrate AND Forced Vital Capacity less than 70% AND DLCO less than 60% at steady state
• Confirmed pulmonary hypertension defined by a right heart catheterization (PAPm\>25mmHg). Right heart catheterization is required if tricuspid regurgitation velocity \>2.8m/s on cardiac echocardiograph OR \>2.5m/s with an abnormal Brain Natriuretic Peptide dosage or an important decrease in transcutaneous Hb O2 saturation during the 6 minutes walk test.
• Seropositivity for HIV (Human Immunodeficiency Virus), HCV (Hepatitis C Virus), HTLV-1 (Human T-Lymphotropic Virus), or active Hepatitis B Virus, or active infection by CMV or parvovirus B19, based on positive blood PCR.
• Pregnancy or breastfeeding in a postpartum female
• Any current cancer or prior history of a malignant disease, with the exception of curatively treated non-melanoma skin cancer

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Department of Biotherapy, Necker-Enfants Malades Hospital

Paris, 75015, France

Location

Related Publications (1)

• Sobrino S, Joseph L, Magrin E, Chalumeau A, Hebert N, Corsia A, Denis A, Roudaut C, Aussel C, Leblanc O, Brusson M, Felix T, Diana JS, Petrichenko A, El Etri J, Godard A, Tibi E, Manceau S, Treluyer JM, Mavilio F, Bushman FD, Marcais A, Castelle M, Neven B, Hermine O, Renolleau S, Magnani A, Asnafi V, El Nemer W, Bartolucci P, Six E, Semeraro M, Miccio A, Cavazzana M. Severe inflammation and lineage skewing are associated with poor engraftment of engineered hematopoietic stem cells in patients with sickle cell disease. Nat Commun. 2025 Apr 1;16(1):3137. doi: 10.1038/s41467-025-58321-4.

  PMID: 40169559 RESULT

MeSH Terms

Conditions

Anemia, Sickle Cell

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

Study Officials

• Pablo BARTULOCCI, MD & PhD

  Department of internal medicine, Henri-Mondor Hospital, Creteil, France.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: May 14, 2019
• First Posted: May 28, 2019
• Study Start: November 12, 2019
• Primary Completion: July 28, 2022
• Study Completion: January 23, 2024
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

FR (1)