Resumen

Este ensayo clínico evaluó la eficacia y seguridad de células madre hematopoyéticas autólogas CD34+ (grupo de diferenciación 34), transducidas ex vivo con el vector lentiviral Lenti-D (también denominado elivaldogene autotemcel o eli-cel), para el tratamiento de la adrenoleucodistrofia cerebral (CALD). Las células madre sanguíneas del participante fueron recolectadas y modificadas (transducidas) utilizando el vector lentiviral Lenti-D que codifica la proteína de la adrenoleucodistrofia humana. Después de la modificación (transducción) con el vector lentiviral Lenti-D, las células fueron trasplantadas de vuelta al participante tras un acondicionamiento mieloablativo. Los participantes de este estudio serán seguidos de forma continua en el estudio LTF-304.

Descripción detallada

Para el estudio ALD-102, la población de trasplante (TP), la población con prendimiento de neutrófilos (NEP) y la población con intención de tratar (ITT) fueron idénticas.

Elegibilidad

Edad máxima: 17 YearsSexo: MALE

Criterios de inclusión

Informed consent was obtained from a competent custodial parent or guardian with legal capacity to execute a local institutional review board (IRB)/Independent Ethics Committee (IEC) approved consent (informed assent will be sought from capable participants, in accordance with the directive of the IRB/IEC and with local requirements).
Males aged 17 years and younger, at the time of parental/guardian consent and, where appropriate, participant assent.
Active cerebral adrenoleukodystrophy (ALD) as defined by:
Elevated very long chain fatty acids (VLCFA) values, and
Active CNS disease established by central radiographic review of brain magnetic resonance imaging (MRI) demonstrating:
Loes score between 0.5 and 9 (inclusive) on the 34-point scale, and
Gadolinium enhancement on MRI of demyelinating lesions.
NFS less than or equal to (\<or=) 1.

Criterios de exclusión

Receipt of an allogeneic transplant or gene therapy.
Availability of a willing 10/10 HLA-matched sibling donor (excluding female heterozygotes).
Use of statins, Lorenzo's Oil, or dietary regimens used to lower very long chain fatty acids (VLCFA) levels. Note: participants must discontinue use of these medications at time of consent.
Receipt of an investigational study drug or procedure within 3 months before Screening that might confound study outcomes. Use of investigational study drugs is prohibited throughout the course of the study.
Any conditions that make it impossible to perform MRI studies (including allergies to anesthetics or contrast agents).
Hematological compromise as evidenced by:
Peripheral blood absolute neutrophil count (ANC) count \< 1500 cells/ cubic milli meter (mm3),
Platelet count \< 100,000 cells/mm3, or
Hemoglobin \< 10 gram per deciliter (g/dL).
Uncorrected bleeding disorder.
Hepatic compromise as evidenced by:
Aspartate transaminase (AST) value \> 2.5×upper limit of normal (ULN)
Alanine transaminase (ALT) value \> 2.5×ULN
Total bilirubin value \> 3.0 milligram per deciliter (mg/dL), except if there is a diagnosis of Gilbert's Syndrome and the participant is otherwise stable
Renal compromise as evidenced by abnormal renal function (actual or calculated creatinine clearance \< 50 milliliter per minute \[mL/min\])
Cardiac compromise as evidenced by left ventricular ejection fraction \<40 percent (%)
Immediate family member with a known or suspected Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary non-polyposis colorectal cancer syndrome, and familial adenomatous polyposis).
Clinically significant active bacterial, viral, fungal, parasitic, or prion-associated infection
Positive for human immunodeficiency virus type 1 or 2 (HIV-1, HIV-2); hepatitis B; hepatitis C; human T lymphotrophic virus 1 (HTLV-1). (Note that participants who have been vaccinated against hepatitis B \[hepatitis B surface antibody-positive\] who are negative for other markers of prior hepatitis B infection \[eg, negative for hepatitis B core antibody (Ab)\] are eligible. Participants with past exposure to hepatitis B virus (HBV \[HBcAb positive and/or HBeAb positive\]) are also eligible for the study provided they have a negative test for HBV DNA. Also note that participants who are positive for anti-hepatitis C antibody are eligible as long as they have a negative hepatitis C viral load.
Any clinically significant cardiovascular or pulmonary disease, or other disease or condition that would be contraindicated for any of the other study procedures.
Absence of adequate contraception for fertile participants. Male participants and their female partners are required to use two different effective methods of contraception from Screening through at least 6 months after drug product infusion. If subjects are truly sexually abstinent (where true sexual abstinence is defined as being in line with the preferred and usual lifestyle of the subject), no second method is required.
Any contraindications to the use of granulocyte colony stimulating (G-CSF) during the mobilization of HSCs, and any contraindications to the use of busulfan or cyclophosphamide, including known hypersensitivity to the active substances or to any of the excipients in their formulations.

Estudio de fase 2/3 sobre la eficacia y seguridad de células madre hematopoyéticas transducidas con el vector lentiviral Lenti-D para el tratamiento de la adrenoleucodistrofia cerebral (CALD)

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Lenti-D Drug Product (eli-cel)

Ubicaciones

Medeos SRL

Patrocinadores