Gene therapy using a person's own modified cells for sickle cell disease

Trial details

Who runs it

Assistance Publique - Hôpitaux de Paris

Trial code

NCT07432867

Record updated

4 March 2026

Original description

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 full original descriptionShow less

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.

Inclusion: 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.

Exclusion: Two alpha deletions (risk of alpha-thalassemia after gene therapy); Patients who have already been treated with gene therapy; Evaluations within 6 months prior to screening visit:; Any current cancer or prior history of a malignant disease, with the exception of curatively treated non-melanoma skin cancer; Patients who failed previous HSCT; Participation in another clinical study with an investigational drug within 30 days of screening; Hypersensitivity to the active substances of the administered drugs (plerixafor, busulfan, anti-inflammatory therapy) or to any of their excipients; 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%); 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; 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; Any clinically significant active infection; 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; 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; ALT or AST >3 times ULN; Measured GFR <60ml/min/1.73 m²; Cardiac evaluation: LVEF <40% by cardiac echocardiogram or by MUGA scan or clinically significant ECG abnormalities; 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; 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; Lung interstitial infiltrate AND Forced Vital Capacity less than 70% AND DLCO less than 60% at steady state; Pregnancy or breastfeeding in a postpartum female.

ClinicalTrials.gov NCT07432867