Standard of Care Comparative Arm of Phase 1/2 Gene Therapy Trial DREPAMIR" in Severe Sickle Cell Disease Patients

Starting soon · Not applicable

Conditions studied: Sickle Cell Disease (SCD), Vaso-occlusive Events

In brief

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).

Key facts

Study ID

NCT07752043

Run by

Assistance Publique - Hôpitaux de Paris

People needed

30

Starts

2026-09-01

Expected to finish

2030-03-01

Last updated by the study team

2026-08-07

Who can join

Age: 12 and older, up to 35. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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
• 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
• 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)
• 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.

Where it is running

• Necker-Enfants Malades Hospital, Apheresis Unit — Paris, Île-de-France Region, France

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.