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.

NCT07432867 | Recruiting Phase 1 DMC

• 2 other identifiers: APHP2416642025-521257-17
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Sickle Cell Disease

Keywords

Sickle Cell Disease; Gene therapy; Lentiviral vector; Vaso-occlusive events; CD34+ hematopoietic stem cells; Hematopoietic stem cells transplantation

Outcome Measures

Primary Outcomes (9)

• Neutrophil recovery

  Neutrophil recovery defined as the first of three consecutive days with an ANC of \> 500/µL

  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

  within the 24 months following IV infusion of DREAM01

• In vivo engraftment (neutrophils and platelets)

  hematopoietic reconstitution after IV infusion of the drug product

  every 3 months between 3 to 24 months following IV infusion of DREAM01

• Adverse event

  Adverse event will be measured using CTCAE

  within the 24 months following IV infusion of DREAM01

• Transplant-related mortality (TRM)

  Transplant-related mortality

  within 100 days following IV infusion of DREAM01

• Transplant-related mortality (TRM)

  Transplant-related mortality

  within the first year following IV infusion of DREAM01

• All-cause mortality

  Mortality

  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

  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

  within the 3 months following administration of anti-inflammatory therapy

Secondary Outcomes (52)

• Annualized rate of VOE

  Up to the 24 months following IV infusion of DREAM01

• Transfusion requirement

  Up to the 24 months following IV infusion of DREAM01

• Change in number of units of RBCs transfused

  Up to the 24 months following IV infusion of DREAM01

• Percentage of HbAS3

  Up to the 24 months following IV infusion of DREAM01

• Percentage of HbS

  Up to the 24 months following IV infusion of DREAM01

Study Arms (1)

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

Genetic: DREAM01 drug product; Drug: anti-inflammatory therapy

Interventions

DREAM01 drug product GENETIC

Each patient will receive a single IV infusion of DREAM01, autologous CD34+ stem cells transduced with βAS3m/miR7m lentiviral vector

DREPAMIR drug product

anti-inflammatory therapy DRUG

Patient will receive anti-inflammatory therapy if necessary

DREPAMIR drug product

Eligibility Criteria

• Age: 12 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Imagine Institute: collaborator
• URC-CIC Paris Descartes Necker Cochin: collaborator
• Association Française contre les Myopathies (AFM), Paris: collaborator

Study Sites (1)

Department of Biotherapy, Necker-Enfants Malades Hospital

Paris, Île-de-France Region, 75015, France

RECRUITING

Related Publications (3)

• 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.

  PMID: 35075288 BACKGROUND

• Brusson 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.

  PMID: 37090420 BACKGROUND

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

  PMID: 40169559 BACKGROUND

MeSH Terms

Conditions

Anemia, Sickle Cell; Vaso-Occlusive Crises

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Elisa MAGRIN, PhD

  Department of Biotherapy, Necker-Enfants Malades Hospital

  STUDY DIRECTOR

Central Study Contacts

Marina CAVAZZANA, MD, PhD

CONTACT

01 44 49 50 68; m.cavazzana@aphp.fr

Nelly BRIAND, PhD

CONTACT

01 44 38 18 62; nelly.briand@aphp.fr

Study Design

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

Study Record Dates

• First Submitted: January 2, 2026
• First Posted: February 25, 2026
• Study Start: February 25, 2026
• Primary Completion (Estimated): February 1, 2032
• Study Completion (Estimated): February 1, 2033
• Last Updated: March 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)