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

NCT07752043 | Not Yet Recruiting

• 2 other identifiers: APHP260040ID-RCB Number
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Sickle Cell Disease (SCD); Vaso-occlusive Events

Keywords

Sickle cell disease; Vaso-occlusive events

Outcome Measures

Primary Outcomes (3)

• Disease-related mortality

  Up to the 24 months follow-up

• All-cause mortality

  Up to the 24 months follow-up

• Occurrence of vaso-occlusive events

  between 3 and 15 months following IV infusion of DREAM01 of the corresponding matched DREPAMIR patient

Secondary Outcomes (69)

• Percentage of HbS

  Up to the 24 months follow-up

• Percentage of HbF

  Up to the 24 months follow-up

• Rate of Hemolysis

  Up to the 24 months follow-up

• Rate of Anemia

  Up to the 24 months follow-up

• Transfusion requirement

  Up to the 24 months follow-up

Study Arms (1)

Standard of care

OTHER

Standard of care

Drug: standard of care

Interventions

standard of care DRUG

Supportive management of VOC, long-term RBC transfusions, and foetal haemoglobin (HbF) induction with hydroxyurea (HU) Myocardic MRI (evaluation of function and fibrosis) + hematocrit measurement QoL questionnaires Imaging (brain MRI, transcranial and cervical ultrasound) Cardiac US, ECG Cardiac and Liver MRI (Fe assessment) Physical ability assessments Neuropsychological assessments Fertility

Standard of care

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
• 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.

Sponsors & Collaborators

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

Study Sites (1)

Necker-Enfants Malades Hospital, Apheresis Unit

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

Location

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

Interventions

Standard of Care

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

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Marina CAVAZZANA, MD, PhD

  Department of Biotherapy, Necker-Enfants Malades Hospital

  STUDY DIRECTOR

Central Study Contacts

Joseph LAURE, MD, PhD

CONTACT

01 44 49 55 91; laure.joseph@aphp.fr

Nelly BRIAND, PHD

CONTACT

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2026
• First Posted: August 7, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2030
• Last Updated: August 7, 2026

Record last verified: 2026-07

Locations

FR (1)