Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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) (DREPAGLOBE)

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.
 
ClinicalTrials.gov Identifier: NCT03964792
Recruitment Status : Not yet recruiting
First Posted : May 28, 2019
Last Update Posted : October 29, 2019
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

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)

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Genetic: DREPAGLOBE drug product Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Open Label Study Evaluating 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)
Estimated Study Start Date : November 15, 2019
Estimated Primary Completion Date : February 15, 2022
Estimated Study Completion Date : November 15, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: DREPAGLOBE drug product
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
Each patient will receive a single IV infusion of DREPAGLOBE drug product




Primary Outcome Measures :
  1. Incidence of transplant related mortality [ Time Frame: up to 100 days post treatment ]
    To evaluate the procedure safety

  2. Incidence of the need for rescue autologous bone marrow transplant [ Time Frame: up to 100 days post treatment ]
    To evaluate the procedure safety

  3. Frequency and severity of AEs post transplant transplant [ Time Frame: 6 months post-transplant ]
    Based on the United States national Cancer Institute Common Terminology Criteria for Adverse Events v4.03 To evaluate the procedure safety

  4. Incidence of vector-derived Replication competent lentivirus (RCL) [ Time Frame: 6 months post-transplant ]
    To evaluate the procedure safety

  5. Incidence of clinically detectable malignancy and/or abnormal clonal dominance assessed as related to study treatment [ Time Frame: 6 months post-transplant ]
    To evaluate the procedure safety.It will be evaluated by vector insertion site analysis (VISA.


Secondary Outcome Measures :
  1. Concentration of neutrophil [ Time Frame: 6 months post-transplant ]
    To evaluate the efficacy

  2. Concentration of platelet [ Time Frame: 6 months post-transplant ]
    To evaluate the efficacy. It will be quantified by High performance liquid chromatography

  3. Percentage HbAS3 [ Time Frame: 6 months post-transplant ]
    To evaluate the efficacy. It will be quantified by High performance liquid chromatography It will be quantified by High performance liquid chromatography

  4. Frequency and severity of adverse events [ Time Frame: 24 months post-transplant ]
    based on the United States national Cancer Institute Common Terminology Criteria for Adverse Events v4.03 To evaluate the long -term safety

  5. Absence of RCL (Replication competent lentivirus) [ Time Frame: 24 months post-transplant ]
    To evaluate the long -term safety

  6. Absence of clinically detectable malignancy or abnormal clonal dominance assessed as related to study treatment [ Time Frame: 24 months post-transplant ]
    To evaluate the long -term safety. It will be evaluated by vector insertion site analysis (VISA).

  7. Protein expression through percentage of anti-sickling Hb [ Time Frame: 24 months post-transplant ]
    To evaluate the long -term efficacy



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   5 Years to 35 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • - Age 5 - 35 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)

Exclusion Criteria:

  • 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
  • Immediate family member with an established or suspected Familial Cancer Syndrome
  • Diagnosis of significant psychiatric disorder of the subject that could seriously impeded the ability to participate in the study
  • Patients who failed previous HSCT and are severely ill
  • Any clinically significant active infection
  • Participation in another clinical study with an investigational drug within 30 days of screening
  • Any condition, based on perspective of the medical monitor and treating investigator, which may lead to increased safety risk or inability to comply with the protocol

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 ClinicalTrials.gov identifier (NCT number): NCT03964792


Contacts
Layout table for location contacts
Contact: Marina CAVAZZANA, MD & PhD +33 144495068 m.cavazzana@aphp.fr
Contact: Valérie JOLAINE, Manager +33 1 42 19 28 79 valerie.jolaine@aphp.fr

Locations
Layout table for location information
France
Department of Biotherapy, Necker-Enfants Malades Hospital
Paris, France, 75015
Contact: Marina CAVAZZANA, MD & PhD    +33 144495068    m.cavazzana@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Layout table for investigator information
Study Director: Pablo BARTULOCCI, MD & PhD Department of internal medicine, Henri-Mondor Hospital, Creteil, France.

Layout table for additonal information
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03964792    
Other Study ID Numbers: P170006J
First Posted: May 28, 2019    Key Record Dates
Last Update Posted: October 29, 2019
Last Verified: October 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn