Sickle Cell DiseasePhase 1/2DREPAMIRNCT07432867
Efficacy Safety Study of Gene Therapy for Sickle Cell DiseaseSCD Using Autologous CD34+ Cells Transduced ex Vivo, Carrying a Corrected Globin Gene and a Silencing RNA.
A Phase 1/2 study testing DREAM01 drug product and anti-inflammatory therapy 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 DREAM01, a gene therapy for Sickle Cell Disease (SCD). The therapy consists of transplanting autologous CD34+ cells transduced ex vivo with a bifunctional lentiviral vector expressing βAS3m-globin and an anti-βS miRNA. Read more about this study
- Who is it for?
- Ages 12 to 35 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- DREAM01 drug product and anti-inflammatory therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteFrance
- Study dates
- 25 Feb 2026to Feb 2033
- Phase
- Phase 1/2
- 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
- Acceptation of myelogram (bone marrow aspiration)
- 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 enrolment
- One severe acute chest syndrome (ACS) hospitalized in the intensive care unit
Show all 14Show fewer
- 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, 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
- 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
- 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 erythrapheresis 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)
- Hypersensitivity to the active substances of the administered drugs (plerixafor, busulfan, anti-inflammatory therapy) or to any of their excipients
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- Patients who have already been treated with gene therapy
- 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, 1 recruiting
- Recruiting
Department of Biotherapy, Necker-Enfants Malades Hospital
Paris, Île-de-France Region, 75015
Marina CAVAZZANA, MD, PhD, 01 44 49 50 68 ext. +33, m.cavazzana@aphp.fr
About this study
Official title: A Phase 1/2 Open Label Cohort Study Evaluating the Efficacy and Safety of Gene Therapy of the Sickle Cell Disease (SCD) by Transplantation of an Autologous CD34+ Enriched Cell Fraction That Contains Autologous CD34+ Cells Transduced ex Vivo by the Bifunctional βAS3m/miR7m Lentiviral Vector Expressing the Therapeutical Beta-globin βAS3m and a Micro-RNA (miRNA) Targeting Specifically the Endogenous βS-globin mRNA.
The purpose of this study is to evaluate the Safety and Efficacy of DREAM01, a gene therapy for Sickle Cell Disease (SCD). The therapy consists of transplanting autologous CD34+ cells transduced ex vivo with a bifunctional lentiviral vector expressing βAS3m-globin and an anti-βS miRNA. It aims to reduce or eliminate vaso-occlusive events and long-term organ damage in severe SCD patients lacking a Human Leukocyte Antigen (HLA) identical sibling donor.
Read the detailed description
Sickle cell anaemia is a hereditary disease caused by a mutation in the gene for beta haemoglobin, essential for oxygen transport by red blood cells. This genetic mutation causes a deformation of the red blood cells, giving them a crescent shape (also known as a sickle) and leading to their massive destruction, resulting in anaemia. Other serious consequences are linked to this disease, such as recurrent painful obstructive crises, known as vaso-occlusive crises (VOC), as well as strokes, acute respiratory syndromes (ARS) and multi-organ damage. All these complications are linked to the obstruction of capillaries caused by deformed red blood cells.
Management of the disease consists of regular transfusions of healthy red blood cells and/or specific drug therapy such as hydroxyurea (HU). HU increases the production of foetal haemoglobin, which can prevent the deformation of red blood cells characteristic of sickle cell disease. By reducing the number of sickle-shaped red blood cells, hydroxyurea helps reduce the frequency of painful attacks and other complications associated with the disease. During these painful attacks, deformed red blood cells block small blood vessels, leading to intense pain and organ damage. These treatments help prevent the risks associated with the disease, but also entail transfusion-related risks (immunological response that may prevent the necessary transfusion).
The only curative treatment to date is a bone marrow transplant from a compatible sibling donor. Bone marrow contains stem cells capable of producing blood cells (red blood cells, white blood cells and platelets) throughout an individual's life. Unfortunately, this treatment is only available for 25% of patients, and is associated with significant immunological complications caused by the white blood cells present in the graft (graft-versus-host disease) or risk of rejection (if partially compatible donor). The aim of this study is to treat patients with severe sickle cell disease with a new experimental gene therapy treatment. This is a new therapeutic approach for patients without a compatible donor, and patients will be followed for 2 years.
- Conditions
- Sickle Cell Disease
- Being tested
- DREAM01 drug product, anti-inflammatory therapy
- Keywords
- Sickle Cell Disease, Gene therapy, Lentiviral vector, Vaso-occlusive events, CD34+ hematopoietic stem cells, Hematopoietic stem cells transplantation
- 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.
DREAM01 drug productGenetic
Each patient will receive a single IV infusion of DREAM01, autologous CD34+ stem cells transduced with βAS3m/miR7m lentiviral vector
anti-inflammatory therapyDrug
Patient will receive anti-inflammatory therapy if necessary
| Study group | Role | What they receive |
|---|---|---|
| DREPAMIR drug product | Experimental | DREAM01 is a genetically modified cell therapy product that consists of autologous CD34+ cells transduced ex vivo by the bifunctional βAS3m/mR7m lentiviral vector expressing the βAS3m-globin and a micro-RNA (miRNA) targeting specifically the endogenous sickle βS-globin gene.
With or without prior administration of an anti-inflammatory therapy in case of severe inflammation detected at the inclusion phase Receives: Genetic: DREAM01 drug product; Drug: anti-inflammatory therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neutrophil recovery
Neutrophil recovery defined as the first of three consecutive days with an ANC of > 500/µL
Measured: within the 24 months following IV infusion of DREAM01
Platelet recovery
Platelet recovery defined as the first of three consecutive days with a platelet count of > 20.000/µL sustained without platelet transfusion for at least seven days
Measured: within the 24 months following IV infusion of DREAM01
In vivo engraftment (neutrophils and platelets)
hematopoietic reconstitution after IV infusion of the drug product
Measured: every 3 months between 3 to 24 months following IV infusion of DREAM01
Adverse event
Adverse event will be measured using CTCAE
Measured: within the 24 months following IV infusion of DREAM01
Transplant-related mortality (TRM)
Transplant-related mortality
Measured: within 100 days following IV infusion of DREAM01
Transplant-related mortality (TRM)
Transplant-related mortality
Measured: within the first year following IV infusion of DREAM01
All-cause mortality
Mortality
Measured: Up to the 24 months following IV infusion of DREAM01
Efficacy of DREAM01
absence of vaso-occlusive events (VOE) in patients who have discontinued the transfusion program or/and hydroxyurea
Measured: between 3 and 15 months following IV infusion of DREAM01
Efficacy of anti-inflammatory therapy
Decrease of HSPCs inflammation assessed through a reduction of the score and/or the number of inflammatory pathways (among the 6 pathways established) by transcriptomic analysis on HSPCs between inclusion and after 3 months of anti-inflammatory therapy treatment before infusion
Measured: within the 3 months following administration of anti-inflammatory therapy
Secondary outcomes (52)
Annualized rate of VOE
Proportion of subjects with reduction in annualized rate of VOE at the time of analysis from baseline by at least 90% up to 24 months after DREAM01 infusion
Measured: Up to the 24 months following IV infusion of DREAM01
Transfusion requirement
Number of transfusion requirement
Measured: Up to the 24 months following IV infusion of DREAM01
Change in number of units of RBCs transfused
change in number of units of RBCs transfused for SCD-related indications over time
Measured: Up to the 24 months following IV infusion of DREAM01
Percentage of HbAS3
Measure of HbAS3
Measured: Up to the 24 months following IV infusion of DREAM01
Percentage of HbS
Measure of Measure of HbS
Measured: Up to the 24 months following IV infusion of DREAM01
Quantification of the transgene copy number (VCN)
Quantification of the transgene copy number (VCN) on drug substance at time of cryopreservation, on PBMC, sorted T-CD3+ and sorted NK cells
Measured: Up to the 24 months following IV infusion of DREAM01
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 following IV infusion of DREAM01
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 following IV infusion of DREAM01
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 following IV infusion of DREAM01
Changes in brain function
Occurrence of pathological flow acceleration or vascular stenosis using carotid and transcranial Doppler ultrasound
Measured: Up to the 24 months following IV infusion of DREAM01
Changes in ocular function
Assessed Using Fundus examination
Measured: Up to the 24 months following IV infusion of DREAM01
Changes in ocular function
Assessed Using angiography
Measured: Up to the 24 months following IV infusion of DREAM01
Changes in cardiac function
evaluated through electrocardiographic (ECG) assessment
Measured: Up to the 24 months following IV infusion of DREAM01
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, cardiac MRI (including myocardial imaging), Doppler echocardiography and transthoracic echocardiography
Measured: Up to the 24 months following IV infusion of DREAM01
Changes in left ventricular size
Changes in left ventricular size assessed using cardiac ultrasound, cardiac MRI (including myocardial imaging), Doppler echocardiography and transthoracic echocardiography
Measured: Up to the 24 months following IV infusion of DREAM01
Changes in left ventricular wall thickness
Changes in the left ventricular wall thickness assessed using cardiac ultrasound, cardiac MRI (including myocardial imaging), Doppler echocardiography and transthoracic echocardiography
Measured: Up to the 24 months following IV infusion of DREAM01
Changes in systolic pulmonary artery pressure [sPAP]
Changes in systolic pulmonary artery pressure [sPAP], assessed using cardiac ultrasound, cardiac MRI (including myocardial imaging), Doppler echocardiography and transthoracic echocardiography
Measured: Up to the 24 months following IV infusion of DREAM01
Changes in tricuspid regurgitation velocity [TRV]
Changes in tricuspid regurgitation velocity [TRV] assessed using cardiac ultrasound, cardiac MRI (including myocardial imaging), Doppler echocardiography and transthoracic echocardiography
Measured: Up to the 24 months following IV infusion of DREAM01
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 following IV infusion of DREAM01
Change in serum electrolyte panel
Measured: Up to the 24 months following IV infusion of DREAM01
Change in serum creatinine
Measured: Up to the 24 months following IV infusion of DREAM01
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 following IV infusion of DREAM01
Change in urinary microalbumin
Measured: Up to the 24 months following IV infusion of DREAM01
Change in protein excretion
Measured: Up to the 24 months following IV infusion of DREAM01
Change in urinary creatinine
Measured: Up to the 24 months following IV infusion of DREAM01
Changes in creatinine clearence
Measured: Up to the 24 months following IV infusion of DREAM01
Change in liver enzyme AST
Measured: Up to the 24 months following IV infusion of DREAM01
Change in liver enzyme ALT
Measured: Up to the 24 months following IV infusion of DREAM01
Change in liver enzyme GGT
Measured: Up to the 24 months following IV infusion of DREAM01
Changes in in liver enzyme ALP
Measured: Up to the 24 months following IV infusion of DREAM01
Change in total bilirubin
Measured: Up to the 24 months following IV infusion of DREAM01
Change in unconjugated (free) bilirubin
Measured: Up to the 24 months following IV infusion of DREAM01
Changes in hepatic function
Description of hepatic morphology assessed through abdominal ultrasound
Measured: Up to the 24 months following IV infusion of DREAM01
Change in diffusing capacity for carbon monoxide (DLCO)
Measured: Up to the 24 months following IV infusion of DREAM01
Change in vital capacity (VC)
Measured: Up to the 24 months following IV infusion of DREAM01
Change in residual volume (RV)
Measured: Up to the 24 months following IV infusion of DREAM01
Change in FEV1/FVC ratio (Tiffeneau index)
Measured: Up to the 24 months following IV infusion of DREAM01
Changes in bone metabolism
Assessed through Osteodensitometry, osteoarticular MRI
Measured: Up to the 24 months following IV infusion of DREAM01
Changes in muscular function
Assessed through physical capacity testing
Measured: Up to the 24 months following IV infusion of DREAM01
Occurrence of iron overload
Efficacy
Measured: Up to the 24 months following IV infusion of DREAM01
Fertility evaluation
Safety
Measured: Up to the 24 months following IV infusion of DREAM01
Walk ability
6-minute walk-test
Measured: Up to the 24 months following IV infusion of DREAM01
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 following IV infusion of DREAM01
Cardiopulmonary capacity
Cardiopulmonary exercise test, using the Cardio Pulmonary Exercise Test
Measured: Up to the 24 months following IV infusion of DREAM01
Physical ability
Physical ability questionnaire, using the Global physical activity questionnaire (GPAQ) (16 items) developed by WHO
Measured: Up to the 24 months following IV infusion of DREAM01
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
Measured: Up to the 24 months following IV infusion of DREAM01
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.
Measured: Up to the 24 months following IV infusion of DREAM01
Quality of life Evaluation : physical, mental, and social health
PROMIS (Patient-Reported Outcomes Measurement Information System) 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.
Measured: Up to the 24 months following IV infusion of DREAM01
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.
Measured: Up to the 24 months following IV infusion of DREAM01
Changes in brain function
Description of neuropsychological status using functional performance testing
Measured: Up to the 24 months following IV infusion of DREAM01
Change in hepatic function
Occurrence of fibrosis and cirrhosis assessed through Liver elastography
Measured: Up to the 24 months following IV infusion of DREAM01
Change in hepatic function
Occurence of intrahepatic iron deposition assessed through liver MRI
Measured: Up to the 24 months following IV infusion of DREAM01
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2026
- Study start25 Feb 2026
- Primary completionFeb 2032 (estimated)
- Study completionFeb 2033 (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 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
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Imagine Institute, URC-CIC Paris Descartes Necker Cochin, Association Française contre les Myopathies (AFM), Paris
- Responsible party
- Sponsor
- Investigators
- Elisa MAGRIN, PhD, Study director, Department of Biotherapy, Necker-Enfants Malades Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07432867
- Sponsor's protocol ID
- APHP241664
- Other IDs
- 2025-521257-17, 2025
- Acronym
- DREPAMIR
- Status last verified
- Feb 2026
- First submitted
- 2 Jan 2026
- Last updated
- 4 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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 4 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Open Label Cohort Study Evaluating the Efficacy and Safety of Gene Therapy of the Sickle Cell Disease (SCD) by Transplantation of an Autologous CD34+ Enriched Cell Fraction That Contains Autologous CD34+ Cells Transduced ex Vivo by the Bifunctional βAS3m/miR7m Lentiviral Vector Expressing the Therapeutical Beta-globin βAS3m and a Micro-RNA (miRNA) Targeting Specifically the Endogenous βS-globin mRNA.
- ClinicalTrials.gov ID
- NCT07432867
- Acronym / sponsor ID
- DREPAMIR / APHP241664
- Conditions
- Sickle Cell Disease
- Keywords
- Sickle Cell Disease, Gene therapy, Lentiviral vector, Vaso-occlusive events, CD34+ hematopoietic stem cells, Hematopoietic stem cells transplantation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Imagine Institute, URC-CIC Paris Descartes Necker Cochin, Association Française contre les Myopathies (AFM), Paris
- Study start
- 25 Feb 2026 (actual)
- Primary completion
- Feb 2032 (estimated)
- Study completion
- Feb 2033 (estimated)
- First posted
- 25 Feb 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 evaluate the Safety and Efficacy of DREAM01, a gene therapy for Sickle Cell Disease (SCD). The therapy consists of transplanting autologous CD34+ cells transduced ex vivo with a bifunctional lentiviral vector expressing βAS3m-globin and an anti-βS miRNA. It aims to reduce or eliminate vaso-occlusive events and long-term organ damage in severe SCD patients lacking a Human Leukocyte Antigen (HLA) identical sibling donor.
Detailed description
Sickle cell anaemia is a hereditary disease caused by a mutation in the gene for beta haemoglobin, essential for oxygen transport by red blood cells. This genetic mutation causes a deformation of the red blood cells, giving them a crescent shape (also known as a sickle) and leading to their massive destruction, resulting in anaemia. Other serious consequences are linked to this disease, such as recurrent painful obstructive crises, known as vaso-occlusive crises (VOC), as well as strokes, acute respiratory syndromes (ARS) and multi-organ damage. All these complications are linked to the obstruction of capillaries caused by deformed red blood cells.
Management of the disease consists of regular transfusions of healthy red blood cells and/or specific drug therapy such as hydroxyurea (HU). HU increases the production of foetal haemoglobin, which can prevent the deformation of red blood cells characteristic of sickle cell disease. By reducing the number of sickle-shaped red blood cells, hydroxyurea helps reduce the frequency of painful attacks and other complications associated with the disease. During these painful attacks, deformed red blood cells block small blood vessels, leading to intense pain and organ damage. These treatments help prevent the risks associated with the disease, but also entail transfusion-related risks (immunological response that may prevent the necessary transfusion).
The only curative treatment to date is a bone marrow transplant from a compatible sibling donor. Bone marrow contains stem cells capable of producing blood cells (red blood cells, white blood cells and platelets) throughout an individual's life. Unfortunately, this treatment is only available for 25% of patients, and is associated with significant immunological complications caused by the white blood cells present in the graft (graft-versus-host disease) or risk of rejection (if partially compatible donor). The aim of this study is to treat patients with severe sickle cell disease with a new experimental gene therapy treatment. This is a new therapeutic approach for patients without a compatible donor, and patients will be followed for 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DREPAMIR drug product | Experimental | Genetic: DREAM01 drug product, Drug: anti-inflammatory therapyDREAM01 is a genetically modified cell therapy product that consists of autologous CD34+ cells transduced ex vivo by the bifunctional βAS3m/mR7m lentiviral vector expressing the βAS3m-globin and a micro-RNA (miRNA) targeting specifically the endogenous sickle βS-globin gene. With or without prior administration of an anti-inflammatory therapy in case of severe inflammation detected at the inclusion phase |
Who may qualify
- Ages
- 12 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- Age 12 - 35 years
- Acceptation of myelogram (bone marrow aspiration)
- 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:
- Failed hydroxyurea (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
Key exclusion criteria (25 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
- 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 erythrapheresis 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)
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 |
|---|---|---|
| DREAM01 drug productEach patient will receive a single IV infusion of DREAM01, autologous CD34+ stem cells transduced with βAS3m/miR7m lentiviral vector | Genetic | DREPAMIR drug product |
| anti-inflammatory therapyPatient will receive anti-inflammatory therapy if necessary | Drug | DREPAMIR drug product |
Primary outcome
Neutrophil recovery
Time frame: within the 24 months following IV infusion of DREAM01
Neutrophil recovery defined as the first of three consecutive days with an ANC of > 500/µL
Platelet recovery
Time frame: within the 24 months following IV infusion of DREAM01
Platelet recovery defined as the first of three consecutive days with a platelet count of > 20.000/µL sustained without platelet transfusion for at least seven days
In vivo engraftment (neutrophils and platelets)
Time frame: every 3 months between 3 to 24 months following IV infusion of DREAM01
hematopoietic reconstitution after IV infusion of the drug product
Adverse event
Time frame: within the 24 months following IV infusion of DREAM01
Adverse event will be measured using CTCAE
Transplant-related mortality (TRM)
Time frame: within 100 days following IV infusion of DREAM01
Transplant-related mortality
Transplant-related mortality (TRM)
Time frame: within the first year following IV infusion of DREAM01
Transplant-related mortality
All-cause mortality
Time frame: Up to the 24 months following IV infusion of DREAM01
Mortality
Efficacy of DREAM01
Time frame: between 3 and 15 months following IV infusion of DREAM01
absence of vaso-occlusive events (VOE) in patients who have discontinued the transfusion program or/and hydroxyurea
Efficacy of anti-inflammatory therapy
Time frame: within the 3 months following administration of anti-inflammatory therapy
Decrease of HSPCs inflammation assessed through a reduction of the score and/or the number of inflammatory pathways (among the 6 pathways established) by transcriptomic analysis on HSPCs between inclusion and after 3 months of anti-inflammatory therapy treatment before infusion
52 secondary outcomes
Annualized rate of VOE
Time frame: Up to the 24 months following IV infusion of DREAM01
Transfusion requirement
Time frame: Up to the 24 months following IV infusion of DREAM01
Change in number of units of RBCs transfused
Time frame: Up to the 24 months following IV infusion of DREAM01
Percentage of HbAS3
Time frame: Up to the 24 months following IV infusion of DREAM01
Percentage of HbS
Time frame: Up to the 24 months following IV infusion of DREAM01
Quantification of the transgene copy number (VCN)
Time frame: Up to the 24 months following IV infusion of DREAM01
Rate of hemolysis
Time frame: Up to the 24 months following IV infusion of DREAM01
Rate of anemia
Time frame: Up to the 24 months following IV infusion of DREAM01
Changes in brain function
Time frame: Up to the 24 months following IV infusion of DREAM01
Changes in brain function
Time frame: Up to the 24 months following IV infusion of DREAM01
Changes in ocular function
Time frame: Up to the 24 months following IV infusion of DREAM01
Changes in ocular function
Time frame: Up to the 24 months following IV infusion of DREAM01
Changes in cardiac function
Time frame: Up to the 24 months following IV infusion of DREAM01
Changes in the occurrence of left ventricular ejection fraction [LVEF] right and left atrial
Time frame: Up to the 24 months following IV infusion of DREAM01
Changes in left ventricular size
Time frame: Up to the 24 months following IV infusion of DREAM01
Changes in left ventricular wall thickness
Time frame: Up to the 24 months following IV infusion of DREAM01
Changes in systolic pulmonary artery pressure [sPAP]
Time frame: Up to the 24 months following IV infusion of DREAM01
Changes in tricuspid regurgitation velocity [TRV]
Time frame: Up to the 24 months following IV infusion of DREAM01
Changes in E/A ratio
Time frame: Up to the 24 months following IV infusion of DREAM01
Change in serum electrolyte panel
Time frame: Up to the 24 months following IV infusion of DREAM01
Change in serum creatinine
Time frame: Up to the 24 months following IV infusion of DREAM01
Change in estimated glomerular filtration rate (eGFR)
Time frame: Up to the 24 months following IV infusion of DREAM01
Change in urinary microalbumin
Time frame: Up to the 24 months following IV infusion of DREAM01
Change in protein excretion
Time frame: Up to the 24 months following IV infusion of DREAM01
Change in urinary creatinine
Time frame: Up to the 24 months following IV infusion of DREAM01
Changes in creatinine clearence
Time frame: Up to the 24 months following IV infusion of DREAM01
Change in liver enzyme AST
Time frame: Up to the 24 months following IV infusion of DREAM01
Change in liver enzyme ALT
Time frame: Up to the 24 months following IV infusion of DREAM01
Change in liver enzyme GGT
Time frame: Up to the 24 months following IV infusion of DREAM01
Changes in in liver enzyme ALP
Time frame: Up to the 24 months following IV infusion of DREAM01
Change in total bilirubin
Time frame: Up to the 24 months following IV infusion of DREAM01
Change in unconjugated (free) bilirubin
Time frame: Up to the 24 months following IV infusion of DREAM01
Changes in hepatic function
Time frame: Up to the 24 months following IV infusion of DREAM01
Change in diffusing capacity for carbon monoxide (DLCO)
Time frame: Up to the 24 months following IV infusion of DREAM01
Change in vital capacity (VC)
Time frame: Up to the 24 months following IV infusion of DREAM01
Change in residual volume (RV)
Time frame: Up to the 24 months following IV infusion of DREAM01
Change in FEV1/FVC ratio (Tiffeneau index)
Time frame: Up to the 24 months following IV infusion of DREAM01
Changes in bone metabolism
Time frame: Up to the 24 months following IV infusion of DREAM01
Changes in muscular function
Time frame: Up to the 24 months following IV infusion of DREAM01
Occurrence of iron overload
Time frame: Up to the 24 months following IV infusion of DREAM01
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 4 Mar 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.
- Individual participant dataSharing planned: No
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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.
Elisa MAGRIN, 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 Phase 1/2 study testing DREAM01 drug product and anti-inflammatory therapy 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 14 inclusion and 25 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: looking for participants now, as of the sponsor's last update on 4 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?
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 Marina CAVAZZANA, MD, PhD (01 44 49 50 68 ext. +33, m.cavazzana@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neutrophil recovery (time frame: within the 24 months following IV infusion of DREAM01). The study lists 9 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 NCT07432867, 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 4 Mar 2026.