Sickle Cell DiseasePhase 1/2DREPAGLOBENCT03964792
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)
A Phase 1/2 study testing DREPAGLOBE drug product in people with Sickle Cell Disease, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 12 to 20 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- DREPAGLOBE drug product
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteFrance
- Study dates
- 12 Nov 2019to 23 Jan 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- - 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.
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- 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)
Who cannot join
- 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:
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- 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
Trial locations and contacts
1 site in 1 country.
France1 site
Department of Biotherapy, Necker-Enfants Malades Hospital
Paris, 75015
About this study
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)
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
- Being tested
- DREPAGLOBE drug product
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DREPAGLOBE drug productGenetic
Each patient will receive a single IV infusion of DREPAGLOBE drug product
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Genetic: DREPAGLOBE drug product |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of transplant related mortality
To evaluate the procedure safety
Measured: up to 100 days post treatment
Incidence of the need for rescue autologous bone marrow transplant
To evaluate the procedure safety
Measured: 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
Measured: 6 months post-transplant
Incidence of vector-derived Replication competent lentivirus (RCL)
To evaluate the procedure safety
Measured: 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.
Measured: 6 months post-transplant
Secondary outcomes (7)
Concentration of neutrophil
To evaluate the efficacy
Measured: 6 months post-transplant
Concentration of platelet
To evaluate the efficacy. It will be quantified by High performance liquid chromatography
Measured: 6 months post-transplant
Percentage HbAS3
To evaluate the efficacy. It will be quantified by High performance liquid chromatography It will be quantified by High performance liquid chromatography
Measured: 6 months post-transplant
Frequency and severity of adverse events
based on the United States national Cancer Institute Common Terminology Criteria for Adverse Events v4.03 To evaluate the long -term safety
Measured: 24 months post-transplant
Absence of RCL (Replication competent lentivirus)
To evaluate the long -term safety
Measured: 24 months post-transplant
Absence of clinically detectable malignancy or abnormal clonal dominance assessed as related to study treatment
To evaluate the long -term safety. It will be evaluated by vector insertion site analysis (VISA).
Measured: 24 months post-transplant
Protein expression through percentage of anti-sickling Hb
To evaluate the long -term efficacy
Measured: 24 months post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2019
- Study start12 Nov 2019
- Primary completion28 Jul 2022
- Study completion23 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Pablo BARTULOCCI, MD & PhD, Study director, Department of internal medicine, Henri-Mondor Hospital, Creteil, France.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03964792
- Sponsor's protocol ID
- P17006J
- Acronym
- DREPAGLOBE
- Status last verified
- Mar 2026
- First submitted
- 14 May 2019
- Last updated
- 5 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 40169559
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03964792
- Acronym / sponsor ID
- DREPAGLOBE / P17006J
- Conditions
- Sickle Cell Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Study start
- 12 Nov 2019 (actual)
- Primary completion
- 28 Jul 2022 (actual)
- Study completion
- 23 Jan 2024 (actual)
- First posted
- 28 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DREPAGLOBE drug product | Experimental | Genetic: DREPAGLOBE drug productThe 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. |
Who may qualify
- Ages
- 12 to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
- - 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:
- 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%
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DREPAGLOBE drug productEach patient will receive a single IV infusion of DREPAGLOBE drug product | Genetic | DREPAGLOBE drug product |
Primary outcome
Incidence of transplant related mortality
Time frame: up to 100 days post treatment
To evaluate the procedure safety
Incidence of the need for rescue autologous bone marrow transplant
Time frame: up to 100 days post treatment
To evaluate the procedure safety
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
Incidence of vector-derived Replication competent lentivirus (RCL)
Time frame: 6 months post-transplant
To evaluate the procedure safety
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.
7 secondary outcomes
Concentration of neutrophil
Time frame: 6 months post-transplant
Concentration of platelet
Time frame: 6 months post-transplant
Percentage HbAS3
Time frame: 6 months post-transplant
Frequency and severity of adverse events
Time frame: 24 months post-transplant
Absence of RCL (Replication competent lentivirus)
Time frame: 24 months post-transplant
Absence of clinically detectable malignancy or abnormal clonal dominance assessed as related to study treatment
Time frame: 24 months post-transplant
Protein expression through percentage of anti-sickling Hb
Time frame: 24 months post-transplant
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2026.
- Results publication: PubMed 40169559Sobrino 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pablo BARTULOCCI, MD & PhD study director
Department of internal medicine, Henri-Mondor Hospital, Creteil, France.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing DREPAGLOBE drug product in people with Sickle Cell Disease, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of transplant related mortality (time frame: up to 100 days post treatment). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03964792, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2026.