DREAM01 for Sickle cell disease

Inclusion criteria

• {"criterion_text":"- Age 5 – 35 years"}
• {"criterion_text":"- Effective method of contraception : Heterosexual female participants of childbearing potential who have, or may have, male sexual partners during the course of the study should be using an insertable (implant or IUD), injectable, transdermal or combination oral contraceptive approved by the TGA combined with a barrier contraceptive. Abstinent female participants must agree to start a double method if they start a sexual relationship with a male. Female participants must not be planning in vitro fertilisation within the required contraception period. Women of non-childbearing potential who will not require contraception during the trial are defined as: surgically sterile (tubal ligation is not considered surgically sterile), post-menopausal (spontaneous amenorrhoea for ≥12 months, or spontaneous amenorrhoea for 6-12 months and follicle-stimulating hormone (FSH) ≥40 IU/mL; either should be together with the absence of oral contraceptive use for >12months). Male participants who have, or may have female sexual partners must agree to use a double method of contraception including condom plus diaphragm, or condom plus stable insertable (implant or IUD), injectable, transdermal or combination oral contraceptive by the female partner, from the time of informed consent. Abstinent male participants must agree to start a double method if they begin a sexual relationship with a female. Male participants with female partners that are surgically sterile or post-menopausal, or male participants who have undergone sterilisation and have had testing to confirm the success of the sterilisation, may also be included and will not be required to use above described methods of contraception. In addition, all male participants must agree to not donate sperm."}
• {"criterion_text":"- Acceptation of myelogram (bone marrow aspiration)"}
• {"criterion_text":"- Diagnosis of HbSS by Hb electrophoresis and genetic analysis to analyse the alpha locus"}
• {"criterion_text":"- Antécédents cliniques ou signes actuels de drépanocytose sévère avec au moins une des complications cliniques suivantes démontrant la sévérité de la maladie : o\tAu moins 3 crises vaso-occlusives nécessitant une hospitalisation, sous hydroxyurée ou transfusion, dans les 2 années précédant l’inclusion o\tUn syndrome thoracique aigu (STA) grave nécessitant une hospitalisation en unité de soins intensifs o\tAu moins 2 épisodes de STA, dont un survenu sous hydroxyurée o\tPriapisme aigu (au moins 2 épisodes de plus de 3 heures dans l’année précédente ou dans l’année précédant le début d’un programme transfusionnel régulier), OU priapisme récidivant (≥ 1 fois par semaine) sous traitement de la drépanocytose (hydroxyurée, transfusion ou phlébotomie) o\tVitesse de régurgitation tricuspide >2,8 m/s à l’échocardiographie sans hypertension pulmonaire confirmée par cathétérisme cardiaque droit (PAP moyenne >< 25 mmHg)"}
• {"criterion_text":"- Hydroxyurea (HU) treatment failure OR inadequate clinical response to HU."}
• {"criterion_text":"- Karnovsky/Lansky performance score ≥ 60%"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Procedure for obtaining consent (adults, dependent minors, to give their consent)"}
• {"criterion_text":"- Affiliation to social security"}

Exclusion criteria

• {"criterion_text":"- Existence of a matched sibling donor"}
• {"criterion_text":"- Diagnosis of significant psychiatric disorder of the subject that could seriously impede the ability to participate in the study"}
• {"criterion_text":"- Patients who failed previous HSCT"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Any clinically significant active infection"}
• {"criterion_text":"- Participation in another clinical study with an investigational drug within 30 days of screening"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Hematologic evaluation: Leukopenia (WBC <3,000µL) or neutropenia (ANC <1,000µL) or thrombocytopenia (platelet count <100,000µL) within 90 days prior to mobilization or harvest (not due to an erytrapheresis procedure or possible acute viral infection)"}
• {"criterion_text":"- PT/INR or PTT >1.5 times the upper limit of normal (ULN) or clinically significant bleeding disorder"}
• {"criterion_text":"- Two alpha deletions (risk of alpha-thalassemia after gene therapy)"}
• {"criterion_text":"- ALT or AST >3 times ULN"}
• {"criterion_text":"- Stroke with significant CNS sequelae i.e., Rankin >2"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Measured GFR <60ml/min/1.73 m²"}
• {"criterion_text":"- Cardiac evaluation: LVEF <40% by cardiac echocardiogram or by MUGA scan or clinically significant ECG abnormalities"}
• {"criterion_text":"- Hypersensitivity to the active substances of the administered drugs or to any of their excipients"}
• {"criterion_text":"- Patients who have already been treated with gene therapy"}
• {"criterion_text":"- 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%)"}
• {"criterion_text":"- Lung interstitial infiltrate AND Forced Vital Capacity less than 70% AND DLCO less than 60% at steady state"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Pregnancy or breastfeeding in a postpartum female"}
• {"criterion_text":"- Any current cancer or prior history of a malignant disease, with the exception of curatively treated non-melanoma skin cancer"}
• {"criterion_text":"- Immediate family member with an established or suspected Familial Cancer Syndrome"}

Primary endpoints

• {"endpoint_text":"- Efficacy and safety after intravenous infusion of DREAM01 gene therapy with or without prior administration of Imatinib treatment.","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- 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. The evaluation starts 60 days after the last RBC transfusion for post-transplant support or SCD disease management","definition_or_measurement_approach":"Reduction in annualized rate of vaso-occlusive events (VOE) from baseline by ≥90%; evaluation begins 60 days after last RBC transfusion and assessed up to 24 months post-infusion."}
• {"endpoint_text":"- Transfusion requirement and change in number of units of RBCs transfused for SCD-related indications over time","definition_or_measurement_approach":"Measured as transfusion requirement and change in number of RBC units transfused for SCD-related indications over time."}
• {"endpoint_text":"- Percentage of HbAS3 and HbS over time","definition_or_measurement_approach":"Serial measurement of hemoglobin fractions (HbAS3 and HbS) over time."}
• {"endpoint_text":"- Vector copy number over time","definition_or_measurement_approach":"Serial measurement of vector copy number in relevant samples over time."}
• {"endpoint_text":"- Biologic parameters that reflect hemolysis and anemia over time (Total hemoglobin, Reticulocytes, lactate dehydrogenase LDH, circulating erythroblasts, haptoglobin, free plasmatic heme, no conjugated bilirubin, erythropoietin EPO)","definition_or_measurement_approach":"Serial laboratory assessments of listed biomarkers (total hemoglobin, reticulocytes, LDH, circulating erythroblasts, haptoglobin, free plasma heme, unconjugated bilirubin, EPO) over time."}
• {"endpoint_text":"- Biologic, functional and radiologic parameters reflecting organ function that may be affected by the disease or conditioning (evaluation of cerebral, ophthalmic, cardiac, renal, liver, pulmonary, bone, muscular)","definition_or_measurement_approach":"Assessment using biological tests, functional tests and radiologic evaluations of cerebral, ophthalmic, cardiac, renal, hepatic, pulmonary, bone and muscular function."}
• {"endpoint_text":"- Evaluation of iron overload (ferritin, liver and cardiac MRI) and specific treatment (chelator, phlebotomy)","definition_or_measurement_approach":"Assessment of iron overload via ferritin and liver/cardiac MRI; documentation of specific treatments such as chelation or phlebotomy."}
• {"endpoint_text":"- Fertility evaluation: to be adapted according to sex: spermogram, hormone assays (estradiol, LH, FSH, testosterone, etc.), AMH, pelvic ultrasound for follicular count","definition_or_measurement_approach":"Fertility assessments including semen analysis, hormone assays (estradiol, LH, FSH, testosterone), AMH and pelvic ultrasound follicle count as appropriate by sex."}
• {"endpoint_text":"- Physical ability and capacity (6-minute walk-test, vertical jump test, physical ability questionnaire, cardiopulmonary exercise test)","definition_or_measurement_approach":"Functional tests including 6-minute walk test, vertical jump, physical ability questionnaires and cardiopulmonary exercise testing."}
• {"endpoint_text":"- Quality of life Evaluation: SF-36 (Short Form-36 Health Survey), FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue Scale), PROMIS (Patient-Reported Outcomes Measurement Information System) or PedsQL (Pediatric Quality of Life Inventory) Generic Core Scales","definition_or_measurement_approach":"Quality of life measured using SF-36, FACIT-Fatigue, PROMIS or PedsQL generic core scales as appropriate."}

France

Earliest CTIS Part Ii Submission Date

17-10-2025

Latest Decision Or Authorization Date

16-03-2026

Processing Time Days

150

Number Of Sites

12

Number Of Participants

13

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France