Sickle Cell Disease (SCD)Drepamir-socNCT07752043
Standard of Care Comparative Arm of Phase 1/2 Gene Therapy Trial DREPAMIR" in Severe Sickle Cell Disease Patients
A study of Sickle Cell Disease (SCD) and Vaso-occlusive Events, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The purpose of this study is to compare the efficacy and safety of transplantation of gene modified autologous CD34+ cells in SCD patients within a therapeutic strategy that may include anti-inflammatory treatment as a pre-transplant treatment in case of severe inflammation detected at the inclusion analysis; the… Read more about this study
- Who is it for?
- Ages 12 to 35 years
- Conditions the study is for
- Sickle Cell Disease (SCD), Vaso-occlusive Events
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2026to Mar 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age 12 - 35 years
- Diagnosis of HbSS by Hb electrophoresis and genetic analysis to analyse the alpha locus
- 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 the intensive care unit At least 2 episodes of ACS, 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).
- 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 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 crisis requiring hospitalization, requirement of transfusion to maintain Hb >6.0g/dL, an episode of ACS despite adequate supportive care measures
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- 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)
- Procedure for obtaining consent (adults, dependent minors, to give their consent)
- Affiliation to social security
Who cannot join
- Existence of a matched sibling donor
- Based on myelogram, the presence of chromosomal (detected by karyotyping) or molecular abnormalities (detected by NGS) and retained dangerous by the Hemato-Oncology referent and validated during a specific multidisciplinary concerted meeting
- Patients who have already been treated with gene therapy or BMT
- Hematologic evaluation: Leukopenia (WBC <3,000/µL) or neutropenia (ANC <1,000/µL) or thrombocytopenia (platelet count <100,000/µL) within 90 days prior to mobilization or harvest (not due to an erytrapheresis procedure or possible acute viral infection)
- PT/INR or PTT >1.5 times the upper limit of normal (ULN) or clinically significant bleeding disorder
- Two alpha deletions (risk of alpha-thalassemia after gene therapy)
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- Evaluations within 6 months prior to screening visit:
- ALT or AST >3 times ULN
- Severe liver iron overload evaluated by MRI (>15mg Fe/g dry weight or >270umol Fe/g dry weight) or liver cirrhosis suspicion on echography or elastometry or CT scan or MRI AND confirmed by histology
- Measured GFR <60ml/min/1.73 m²
- Cardiac evaluation: LVEF <40% by cardiac echocardiogram or by MUGA scan or clinically significant ECG abnormalities
- Stroke with significant CNS sequelae i.e., Rankin >2
- Specific sickle cell disease cerebral vasculopathy confirmed by MRA (magnetic resonance angiography) OR transcranial doppler ultrasound with or without Moya-moya WITH an indication of chronic transfusion program (target HbS<30%)
- 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 >25 mmHg). 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 impede the ability to participate in the study
- Patients who failed previous HSCT
- 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. Contact the study team or a site near you to ask about taking part.
France1 site
Necker-Enfants Malades Hospital, Apheresis Unit
Paris, Île-de-France Region, 75015
Joseph LAURE, MD, PhD, 01 44 49 55 91 ext. +33, laure.joseph@aphp.fr
About this study
The purpose of this study is to compare the efficacy and safety of transplantation of gene modified autologous CD34+ cells in SCD patients within a therapeutic strategy that may include anti-inflammatory treatment as a pre-transplant treatment in case of severe inflammation detected at the inclusion analysis; the autologous CD34+ cell will be transduced by the bifunctional βAS3m/miR7m lentiviral vector expressing the therapeutical beta-globin, βAS3m, and the miRNA anti-HbS vs Standard Of Care (SOC).
Read the detailed description
Sickle cell disease is a severe hemoglobinopathy characterized by anemia, chronic hemolysis, and vaso-occlusive crises, leading to high morbidity and mortality.
Medical management options or Standard Of Care (SOC) currently available for SCD include supportive management of VOC, long-term RBC transfusions, and foetal haemoglobin (HbF) induction with hydroxyurea (HU).
Hematopoietic stem cell transplantation is curative but available only for a minority of patients. Gene therapy approaches (gene addition or gene editing) have shown significant reductions in vaso-occlusive events, but residual hemolysis persists and their truly curative potential remains uncertain.
In France, the absence of a control arm in clinical trials has limited regulatory approval, supporting the development of the DREPAMIR protocol, which incorporates a Standard Of Care control group to better assess the efficacy clinical value and cost effectiveness of gene therapy in severe sickle cell disease.
The aim of this study is to compare the efficacy and safety of transplantation of gene modified autologous CD34+ cells in SCD patients within a therapeutic strategy that may include anti-inflammatory treatment as a pre-transplant treatment in case of severe inflammation detected at the inclusion analysis; the autologous CD34+ cell will be transduced by the bifunctional βAS3m/miR7m lentiviral vector expressing the therapeutical beta-globin, βAS3m, and the miRNA anti-HbS vs Standard Of Care (SOC).
Drepamir-SOC is the control arm of the main study DREPAMIR (NCT07432867)
- Conditions
- Sickle Cell Disease (SCD), Vaso-occlusive Events
- Being tested
- standard of care
- Keywords
- Sickle cell disease, Vaso-occlusive events
- Medical subject headings
- Anemia, Sickle Cell, Vaso-Occlusive Crises
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
standard of careDrug
Supportive management of VOC, long-term RBC transfusions, and foetal haemoglobin (HbF) induction with hydroxyurea (HU) Myocardic MRI (evaluation of function and fibrosis) + hematocrit measurement QoL questionnaires Imaging (brain MRI, transcranial and cervical ultrasound) Cardiac US, ECG Cardiac and Liver MRI (Fe assessment) Physical ability assessments Neuropsychological assessments Fertility
| Study group | Role | What they receive |
|---|---|---|
| Standard of care | Other | Standard of care Receives: Drug: standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-related mortality
Measured: Up to the 24 months follow-up
All-cause mortality
Measured: Up to the 24 months follow-up
Occurrence of vaso-occlusive events
Measured: between 3 and 15 months following IV infusion of DREAM01 of the corresponding matched DREPAMIR patient
Secondary outcomes (69)
Percentage of HbS
Measure of HbS
Measured: Up to the 24 months follow-up
Percentage of HbF
Measure of HbF
Measured: Up to the 24 months follow-up
Rate of Hemolysis
Biological parameters that reflect hemolysis : Total hemoglobin, Reticulocytes, lactate dehydrogenase LDH, circulating erythroblasts, haptoglobin, free plasmatic heme, no conjugated bilirubin, erythropoietin EPO
Measured: Up to the 24 months follow-up
Rate of Anemia
Biological parameters that reflect anemia : Total hemoglobin, Reticulocytes, lactate dehydrogenase LDH, circulating erythroblasts, haptoglobin, free plasmatic heme, no conjugated bilirubin, erythropoietin EPO
Measured: Up to the 24 months follow-up
Transfusion requirement
absence of vaso-occlusive events (VOE) in patients who have discontinued the transfusion program or/and hydroxyurea
Measured: Up to the 24 months follow-up
Change in number of units of RBCs transfused
Measured: Up to the 24 months follow-up
Changes in brain function
Occurrence of ischemic lesions, vascular stenosis, aneurysm assessed using cervical doppler ultrasound and cerebral MRI
Measured: Up to the 24 months follow-up
Changes in brain function
Occurrence of pathological flow acceleration or vascular stenosis using carotid and transcranial Doppler ultrasound
Measured: Up to the 24 months follow-up
Changes in ocular function
Assessed Using Fundus examination
Measured: Up to the 24 months follow-up
Changes in ocular function
Assessed Using angiography
Measured: Up to the 24 months follow-up
Changes in cardiac function
Evaluated through electrocardiographic (ECG) assessment : overall interpretation with 3 categories such as Normal/ Abnormal, not clinically significant/ Abnormal, clinically significant
Measured: Up to the 24 months follow-up
Changes in the occurrence of left ventricular ejection fraction [LVEF] right and left atrial
Occurrence of left ventricular ejection fraction [LVEF], right and left atrial, left assessed using cardiac ultrasound.
Measured: Up to the 24 months follow-up
Changes in the occurrence of left ventricular ejection fraction [LVEF] right and left atrial
Occurrence of left ventricular ejection fraction [LVEF], right and left atrial, left assessed using cardiac MRI (including myocardial imaging)
Measured: Up to the 24 months follow-up
Changes in the occurrence of left ventricular ejection fraction [LVEF] right and left atrial
Occurrence of left ventricular ejection fraction [LVEF], right and left atrial, left assessed using Doppler echocardiography.
Measured: Up to the 24 months follow-up
Changes in the occurrence of left ventricular ejection fraction [LVEF] right and left atrial
Occurrence of left ventricular ejection fraction [LVEF], right and left atrial, left assessed using transthoracic echocardiography
Measured: Up to the 24 months follow-up
Changes in left ventricular size
Changes in left ventricular size assessed using cardiac ultrasound.
Measured: Up to the 24 months follow-up
Changes in left ventricular size
Changes in left ventricular size assessed using cardiac MRI (including myocardial imaging)
Measured: Up to the 24 months follow-up
Changes in left ventricular size
Changes in left ventricular size assessed using Doppler echocardiography
Measured: Up to the 24 months follow-up
Changes in left ventricular size
Changes in left ventricular size assessed using transthoracic echocardiography
Measured: Up to the 24 months follow-up
Changes in left ventricular wall thickness
Changes in the left ventricular wall thickness assessed using cardiac ultrasound.
Measured: Up to the 24 months follow-up
Changes in left ventricular wall thickness
Changes in the left ventricular wall thickness assessed using cardiac MRI (including myocardial imaging)
Measured: Up to the 24 months follow-up
Changes in left ventricular wall thickness
Changes in the left ventricular wall thickness assessed using Doppler echocardiography
Measured: Up to the 24 months follow-up
Changes in left ventricular wall thickness
Changes in the left ventricular wall thickness assessed using transthoracic echocardiography
Measured: Up to the 24 months follow-up
Changes in systolic pulmonary artery pressure [sPAP ]
Changes in systolic pulmonary artery pressure [sPAP], assessed using cardiac ultrasound.
Measured: Up to the 24 months follow-up
Changes in systolic pulmonary artery pressure [sPAP ]
Changes in systolic pulmonary artery pressure [sPAP], assessed using cardiac MRI (including myocardial imaging)
Measured: Up to the 24 months follow-up
Changes in systolic pulmonary artery pressure [sPAP ]
Changes in systolic pulmonary artery pressure [sPAP], assessed using Doppler echocardiography
Measured: Up to the 24 months follow-up
Changes in systolic pulmonary artery pressure [sPAP ]
Changes in systolic pulmonary artery pressure [sPAP], assessed using transthoracic echocardiography
Measured: Up to the 24 months follow-up
Changes in tricuspid regurgitation velocity [TRV ]
Changes in tricuspid regurgitation velocity [TRV] assessed using cardiac ultrasound
Measured: Up to the 24 months follow-up
Changes in tricuspid regurgitation velocity [TRV ]
Changes in tricuspid regurgitation velocity [TRV] assessed using cardiac MRI (including myocardial imaging)
Measured: Up to the 24 months follow-up
Title : Changes in tricuspid regurgitation velocity [TRV]
Changes in tricuspid regurgitation velocity [TRV] assessed using Doppler echocardiography
Measured: Up to the 24 months follow-up
Title : Changes in tricuspid regurgitation velocity [TRV]
Changes in tricuspid regurgitation velocity [TRV] assessed using transthoracic echocardiography
Measured: Up to the 24 months follow-up
Changes in E/A ratio
Changes in of E/A ratio assessed using cardiac ultrasound, cardiac MRI (including myocardial imaging), Doppler echocardiography and transthoracic echocardiography
Measured: Up to the 24 months follow-up
Change in serum electrolyte panel
Measured: Up to the 24 months follow-up
Change in serum creatinine
Measured: Up to the 24 months follow-up
Change in estimated glomerular filtration rate (eGFR )
Renal function assessed through estimated glomerular filtration rate (eGFR) calculated using CKD-EPI equation
Measured: Up to the 24 months follow-up
Change in urinary microalbumin
Measured: Up to the 24 months follow-up
Change in protein excretion
Measured: Up to the 24 months follow-up
Change in urinary creatinine
Measured: Up to the 24 months follow-up
Changes in creatinine clearence
Measured: Up to the 24 months follow-up
Change in liver enzyme AST
Measured: Up to the 24 months follow-up
Change in liver enzyme ALT
Measured: Up to the 24 months follow-up
Change in liver enzyme GGT
Measured: Up to the 24 months follow-up
Changes in in liver enzyme ALP
Measured: Up to the 24 months follow-up
Change in total bilirubin
Measured: Up to the 24 months follow-up
Change in unconjugated (free) bilirubin
Measured: Up to the 24 months follow-up
Changes in hepatic function
overall interpretation with 3 categories such as Normal/ Abnormal, not clinically significant/ Abnormal, clinically significant
Measured: Up to the 24 months follow-up
Change in diffusing capacity for carbon monoxide (DLCO )
Measured: Up to the 24 months follow-up
Change in vital capacity (VC )
Measured: Up to the 24 months follow-up
Change in residual volume (RV )
Measured: Up to the 24 months follow-up
Change in FEV1/FVC ratio (Tiffeneau index )
Measured: Up to the 24 months follow-up
Changes in bone metabolism
Assessed through osteodensitometry
Measured: Up to the 24 months follow-up
Changes in muscular function
Overall interpretation with 3 categories such as Normal/ Abnormal, not clinically significant/ Abnormal, clinically significant
Measured: Up to the 24 months follow-up
Occurrence of iron overload
Measured: Up to the 24 months follow-up
Fertility evaluation
Assessed through hormonal testing
Measured: Up to the 24 months follow-up
Quality of life Evaluation: patient health
Medical Outcomes Study Short Form 36 SF-36 The Short Form (36) Health Survey is a 36-item, patient-reported survey of patient health. 0-100 scale so that a higher score indicates a better outcome.
Measured: Up to the 24 months follow-up
Quality of life Evaluation : fatigue
FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue Scale) FACIT-Fatigue is a 13-item self-report scale that assesses fatigue and its effect on daily activities and function. 0-52 scale so that a higher score indicates a better outcome.
Measured: Up to the 24 months follow-up
Quality of life Evaluation: physical , mental, and social health
PROMIS® (Patient-Reported Outcomes Measurement Information System) is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. PROMIS domain scores are reported as T-scores, with a mean of 50 and a standard deviation of 10 in the reference population. Higher scores indicate better health for physical function and ability to participate in social roles and activities, whereas higher scores indicate worse health for fatigue, pain interference, depressive symptoms, anxiety, and sleep disturbance.
Measured: Up to the 24 months follow-up
Health-realted Quality of life Evaluation
Pediatric Quality of Life Inventory (PedsQL ) Generic Core Scales PedsQL is a modular system that assesses health-related quality of life in healthy and ill children and adolescents. It combines generic core scales and disease-specific modules into one measurement system. 0-100 scale, so that higher scores indicate better outcome.
Measured: Up to the 24 months follow-up
Walk ability
6-minute walk-test
Measured: Up to the 24 months follow-up
jump
Vertical jump test : The jump height will be recorded using video analysis software. The average height of the 3 jumps will be calculated
Measured: Up to the 24 months follow-up
Physical ability
physical ability questionnaire, using the Global physical activity questionnaire (GPAQ) (16 items) developed by WHO. Minimum value is 0 with no theoretical maximum value. Higher scores indicate better outcome.
Measured: Up to the 24 months follow-up
Cardiopulmonary capacity
Cardiopulmonary exercise test, using the Cardio Pulmonary Exercise Test
Measured: Up to the 24 months follow-up
Costs
Costs of treatment calculated yearly and cost per event (VOC and ATS)
Measured: Up to the 24 months follow-up
Cost effectiveness
Model-based incremental cost effectiveness ratio of gene therapy with inputs for SoC
Measured: Up to the 24 months follow-up
Changes in cardiac global function
Assessed through cardiac magnetic resonance imaging, using ventricular function - Overall interpretation with 3 categories such as Normal/ Abnormal, not clinically significant/ Abnormal, clinically significant
Measured: Up to the 24 months follow-up
Changes in myocardial tissular
Using late gadolinium myocardial enhancement
Measured: Up to the 24 months follow-up
Changes in myocardial tissular
Using native T1 mapping
Measured: Up to the 24 months follow-up
Changes in myocardial tissular
Using extracellular volume
Measured: Up to the 24 months follow-up
Changes in myocardial tissular
Using diffusion tensor imaging (DTI)
Measured: Up to the 24 months follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2026
- Study startSep 2026 (estimated)
- Primary completionMar 2030 (estimated)
- Study completionMar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell Disease (SCD)Studies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin, Imagine Institute, Association Française contre les Myopathies (AFM), Paris, Marie Lannelongue Hospital
- Responsible party
- Sponsor
- Investigators
- Marina CAVAZZANA, MD, PhD, Study director, Department of Biotherapy, Necker-Enfants Malades Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07752043
- Sponsor's protocol ID
- APHP260040
- Other IDs
- ID-RCB Number
- Acronym
- Drepamir-soc
- Status last verified
- Jul 2026
- First submitted
- 9 Jul 2026
- Last updated
- 7 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Magrin E, Semeraro M, Hebert N, Joseph L, Magnani A, Chalumeau A, Gabrion A, Roudaut C, Marouene J, Lefrere F, Diana JS, Denis A, Neven B, Funck-Brentano I, Negre O, Renolleau S, Brousse V, Kiger L, Touzot F, Poirot C, Bourget P, El Nemer W, Blanche S, Treluyer JM, Asmal M, Walls C, Beuzard Y, Schmidt M, Hacein-Bey-Abina S, Asnafi V, Guichard I, Poiree M, Monpoux F, Touraine P, Brouzes C, de Montalembert M, Payen E, Six E, Ribeil JA, Miccio A, Bartolucci P, Leboulch P, Cavazzana M. Long-term outcomes of lentiviral gene therapy for the beta-hemoglobinopathies: the HGB-205 trial. Nat Med. 2022 Jan;28(1):81-88. doi: 10.1038/s41591-021-01650-w. Epub 2022 Jan 24.
PubMed 35075288Brusson M, Chalumeau A, Martinucci P, Romano O, Felix T, Poletti V, Scaramuzza S, Ramadier S, Masson C, Ferrari G, Mavilio F, Cavazzana M, Amendola M, Miccio A. Novel lentiviral vectors for gene therapy of sickle cell disease combining gene addition and gene silencing strategies. Mol Ther Nucleic Acids. 2023 Mar 22;32:229-246. doi: 10.1016/j.omtn.2023.03.012. eCollection 2023 Jun 13.
PubMed 37090420Sobrino 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 7 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Standard of Care Comparative Arm of Phase 1/2 Gene Therapy Trial DREPAMIR" in Severe Sickle Cell Disease Patients
- ClinicalTrials.gov ID
- NCT07752043
- Acronym / sponsor ID
- Drepamir-soc / APHP260040
- Conditions
- Sickle Cell Disease (SCD), Vaso-occlusive Events
- Keywords
- Sickle cell disease, Vaso-occlusive events
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin, Imagine Institute, Association Française contre les Myopathies (AFM), Paris, Marie Lannelongue Hospital
- Study start
- Sep 2026 (estimated)
- Primary completion
- Mar 2030 (estimated)
- Study completion
- Mar 2030 (estimated)
- First posted
- 7 Aug 2026 (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 compare the efficacy and safety of transplantation of gene modified autologous CD34+ cells in SCD patients within a therapeutic strategy that may include anti-inflammatory treatment as a pre-transplant treatment in case of severe inflammation detected at the inclusion analysis; the autologous CD34+ cell will be transduced by the bifunctional βAS3m/miR7m lentiviral vector expressing the therapeutical beta-globin, βAS3m, and the miRNA anti-HbS vs Standard Of Care (SOC).
Detailed description
Sickle cell disease is a severe hemoglobinopathy characterized by anemia, chronic hemolysis, and vaso-occlusive crises, leading to high morbidity and mortality.
Medical management options or Standard Of Care (SOC) currently available for SCD include supportive management of VOC, long-term RBC transfusions, and foetal haemoglobin (HbF) induction with hydroxyurea (HU).
Hematopoietic stem cell transplantation is curative but available only for a minority of patients. Gene therapy approaches (gene addition or gene editing) have shown significant reductions in vaso-occlusive events, but residual hemolysis persists and their truly curative potential remains uncertain.
In France, the absence of a control arm in clinical trials has limited regulatory approval, supporting the development of the DREPAMIR protocol, which incorporates a Standard Of Care control group to better assess the efficacy clinical value and cost effectiveness of gene therapy in severe sickle cell disease.
The aim of this study is to compare the efficacy and safety of transplantation of gene modified autologous CD34+ cells in SCD patients within a therapeutic strategy that may include anti-inflammatory treatment as a pre-transplant treatment in case of severe inflammation detected at the inclusion analysis; the autologous CD34+ cell will be transduced by the bifunctional βAS3m/miR7m lentiviral vector expressing the therapeutical beta-globin, βAS3m, and the miRNA anti-HbS vs Standard Of Care (SOC).
Drepamir-SOC is the control arm of the main study DREPAMIR (NCT07432867)
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Standard of care | Other | Drug: standard of careStandard of care |
Who may qualify
- Ages
- 12 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- Age 12 - 35 years
- Diagnosis of HbSS by Hb electrophoresis and genetic analysis to analyse the alpha locus
- 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 the intensive care unit At least 2 episodes of ACS, 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).
- Tricuspid regurgitation velocity >2.8m/s on cardiac echocardiograph without pulmonary hypertension confirmed by right heart catheterization (mPAP><25mmHg)
Key exclusion criteria (24 listed)
- Existence of a matched sibling donor
- Based on myelogram, the presence of chromosomal (detected by karyotyping) or molecular abnormalities (detected by NGS) and retained dangerous by the Hemato-Oncology referent and validated during a specific multidisciplinary concerted meeting
- Patients who have already been treated with gene therapy or BMT
- Hematologic evaluation: Leukopenia (WBC <3,000/µL) or neutropenia (ANC <1,000/µL) or thrombocytopenia (platelet count <100,000/µL) within 90 days prior to mobilization or harvest (not due to an erytrapheresis procedure or possible acute viral infection)
- PT/INR or PTT >1.5 times the 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 |
|---|---|---|
| standard of careSupportive management of VOC, long-term RBC transfusions, and foetal haemoglobin (HbF) induction with hydroxyurea (HU) Myocardic MRI (evaluation of function and fibrosis) + hematocrit measurement QoL questionnaires Imaging (brain MRI, transcranial and cervical ultrasound) Cardiac US, ECG Cardiac and Liver MRI (Fe assessment) Physical ability assessments Neuropsychological assessments Fertility | Drug | Standard of care |
Primary outcome
Disease-related mortality
Time frame: Up to the 24 months follow-up
All-cause mortality
Time frame: Up to the 24 months follow-up
Occurrence of vaso-occlusive events
Time frame: between 3 and 15 months following IV infusion of DREAM01 of the corresponding matched DREPAMIR patient
69 secondary outcomes
Percentage of HbS
Time frame: Up to the 24 months follow-up
Percentage of HbF
Time frame: Up to the 24 months follow-up
Rate of Hemolysis
Time frame: Up to the 24 months follow-up
Rate of Anemia
Time frame: Up to the 24 months follow-up
Transfusion requirement
Time frame: Up to the 24 months follow-up
Change in number of units of RBCs transfused
Time frame: Up to the 24 months follow-up
Changes in brain function
Time frame: Up to the 24 months follow-up
Changes in brain function
Time frame: Up to the 24 months follow-up
Changes in ocular function
Time frame: Up to the 24 months follow-up
Changes in ocular function
Time frame: Up to the 24 months follow-up
Changes in cardiac function
Time frame: Up to the 24 months follow-up
Changes in the occurrence of left ventricular ejection fraction [LVEF] right and left atrial
Time frame: Up to the 24 months follow-up
Changes in the occurrence of left ventricular ejection fraction [LVEF] right and left atrial
Time frame: Up to the 24 months follow-up
Changes in the occurrence of left ventricular ejection fraction [LVEF] right and left atrial
Time frame: Up to the 24 months follow-up
Changes in the occurrence of left ventricular ejection fraction [LVEF] right and left atrial
Time frame: Up to the 24 months follow-up
Changes in left ventricular size
Time frame: Up to the 24 months follow-up
Changes in left ventricular size
Time frame: Up to the 24 months follow-up
Changes in left ventricular size
Time frame: Up to the 24 months follow-up
Changes in left ventricular size
Time frame: Up to the 24 months follow-up
Changes in left ventricular wall thickness
Time frame: Up to the 24 months follow-up
Changes in left ventricular wall thickness
Time frame: Up to the 24 months follow-up
Changes in left ventricular wall thickness
Time frame: Up to the 24 months follow-up
Changes in left ventricular wall thickness
Time frame: Up to the 24 months follow-up
Changes in systolic pulmonary artery pressure [sPAP ]
Time frame: Up to the 24 months follow-up
Changes in systolic pulmonary artery pressure [sPAP ]
Time frame: Up to the 24 months follow-up
Changes in systolic pulmonary artery pressure [sPAP ]
Time frame: Up to the 24 months follow-up
Changes in systolic pulmonary artery pressure [sPAP ]
Time frame: Up to the 24 months follow-up
Changes in tricuspid regurgitation velocity [TRV ]
Time frame: Up to the 24 months follow-up
Changes in tricuspid regurgitation velocity [TRV ]
Time frame: Up to the 24 months follow-up
Title : Changes in tricuspid regurgitation velocity [TRV]
Time frame: Up to the 24 months follow-up
Title : Changes in tricuspid regurgitation velocity [TRV]
Time frame: Up to the 24 months follow-up
Changes in E/A ratio
Time frame: Up to the 24 months follow-up
Change in serum electrolyte panel
Time frame: Up to the 24 months follow-up
Change in serum creatinine
Time frame: Up to the 24 months follow-up
Change in estimated glomerular filtration rate (eGFR )
Time frame: Up to the 24 months follow-up
Change in urinary microalbumin
Time frame: Up to the 24 months follow-up
Change in protein excretion
Time frame: Up to the 24 months follow-up
Change in urinary creatinine
Time frame: Up to the 24 months follow-up
Changes in creatinine clearence
Time frame: Up to the 24 months follow-up
Change in liver enzyme AST
Time frame: Up to the 24 months follow-up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2026.
- Background: PubMed 35075288Magrin E, Semeraro M, Hebert N, Joseph L, Magnani A, Chalumeau A, Gabrion A, Roudaut C, Marouene J, Lefrere F, Diana JS, Denis A, Neven B, Funck-Brentano I, Negre O, Renolleau S, Brousse V, Kiger L, Touzot F, Poirot C, Bourget P, El Nemer W, Blanche S, Treluyer JM, Asmal M, Walls C, Beuzard Y, Schmidt M, Hacein-Bey-Abina S, Asnafi V, Guichard I, Poiree M, Monpoux F, Touraine P, Brouzes C, de Montalembert M, Payen E, Six E, Ribeil JA, Miccio A, Bartolucci P, Leboulch P, Cavazzana M. Long-term outcomes of lentiviral gene therapy for the beta-hemoglobinopathies: the HGB-205 trial. Nat Med. 2022 Jan;28(1):81-88. doi: 10.1038/s41591-021-01650-w. Epub 2022 Jan 24.
- Background: PubMed 37090420Brusson M, Chalumeau A, Martinucci P, Romano O, Felix T, Poletti V, Scaramuzza S, Ramadier S, Masson C, Ferrari G, Mavilio F, Cavazzana M, Amendola M, Miccio A. Novel lentiviral vectors for gene therapy of sickle cell disease combining gene addition and gene silencing strategies. Mol Ther Nucleic Acids. 2023 Mar 22;32:229-246. doi: 10.1016/j.omtn.2023.03.012. eCollection 2023 Jun 13.
- Background: 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.
Marina CAVAZZANA, MD, PhD study director
Department of Biotherapy, Necker-Enfants Malades Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study of Sickle Cell Disease (SCD) and Vaso-occlusive Events, 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 10 inclusion and 24 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: opening soon, as of the sponsor's last update on 7 Aug 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Joseph LAURE, MD, PhD (01 44 49 55 91 ext. +33, laure.joseph@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-related mortality (time frame: Up to the 24 months follow-up). The study lists 3 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 NCT07752043, which also lists 3 linked publications.
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 7 Aug 2026; AzTrials last refreshed its copy on 8 Nov 2026.