Phase 3
N=35
A Clinical Study to Assess the Efficacy and Safety of Gene Therapy for the Treatment of Cerebral Adrenoleukodystrophy (CALD)
Cerebral Adrenoleukodystrophy (CALD)
Bottom Line
View on ClinicalTrials.gov: NCT03852498 ↗Enrolled (actual)
35
Serious AEs
62.9%
Results posted
May 2024
Primary outcome: Primary: Percentage of Participants Who Were Alive and Have None of the 6 Major Functional Disabilities (MFDs) at Month 24 — 85.7 Percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Lenti-D (Genetic)
- Age
- Pediatric
- Sex
- Male
- Sponsor
- Genetix Biotherapeutics Inc.
- Primary completion
- Jul 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Who Were Alive and Have None of the 6 Major Functional Disabilities (MFDs) at Month 24 |
85.7 | — |
| PRIMARY Percentage of Participants Who Achieved Neutrophil Engraftment After Drug Product Infusion |
100.0 | — |
| SECONDARY Percentage of Participants Without Gadolinium Enhancement (i.e. GdE-) on Magnetic Resonance Imaging (MRI) at Month 24 |
94.3 | — |
| SECONDARY Number of Participants With Change in Neurologic Function Score (NFS) From Baseline to Month 24 |
4; 2 | — |
| SECONDARY Number of Participants Who Achieved Stable NFS at Month 24 |
33 | — |
| SECONDARY Major Functional Disability (MFD)-Free Survival Rate |
88.6 | — |
| SECONDARY Overall Survival Rate |
100.0 | — |
| SECONDARY Median Detectable Vector Copy Number (VCN) in Peripheral Blood Cells by Month 6 |
1.05 | — |
| SECONDARY Time to Neutrophil Engraftment (NE) After Drug Product Infusion |
14.0 | — |
| SECONDARY Percentage of Participants With Platelet Engraftment by Month 24 |
100.0 | — |
| SECONDARY Time to Platelet Engraftment Post-drug Product Infusion |
29.0 | — |
| SECONDARY Percentage of Participants With Loss of Neutrophil Engraftment Post-drug Product Infusion by Month 24 |
— | — |
| SECONDARY Percentage of Participants Who Underwent a Subsequent Allo- Hematopoietic Stem Cell Transplantation (HSCT) Infusion by Month 24 |
8.6 | — |
| SECONDARY Percentage of Participants Who Experienced Either Acute (>= Grade 2) or Chronic Graft Versus Host Disease (GVHD) at Month 24 |
2.9 | — |
| SECONDARY Percentage of Participants Who Experienced >= Grade 2 Acute Graft Versus Host Disease (GVHD) by Month 24 |
2.9 | — |
| SECONDARY Percentage of Participants Who Experienced Chronic GVHD by Month 24 |
— | — |
| SECONDARY Percentage of Participants Who Experienced Transplant-related Mortality Through 100 and 365 Days Post-drug Product Infusion |
0; 0 | — |
| SECONDARY Percentage of Participants With Clinical >= Grade 3 Adverse Events (AEs), All Investigational Medicinal Product-related AEs, All Serious Adverse Events (SAEs), and >= Grade 3 Infections |
100.0; 20.0; 62.9; 28.6 | — |
| SECONDARY Number of Participants With >= Grade 3 Prolonged Cytopenia on or After Rel Day 60 And Rel Day 100 |
14; 7 | — |
| SECONDARY Percentage of Participants With Potentially Clinically Significant Changes in Laboratory Parameters by Month 24 |
100.0; 2.9; 97.1; 71.4; 100.0; 77.1 | — |
| SECONDARY Number of Emergency Room Visits (Post-Neutrophil Engraftment) by Month 24 |
9 | — |
| SECONDARY Median Number of Emergency Room Visits (Post-Neutrophil Engraftment) by Month 24 |
1.0 | — |
| SECONDARY Number of In-patient Hospitalizations (Post-Neutrophil Engraftment) by Month 24 |
17 | — |
| SECONDARY Median Number of In-patient Hospitalizations (Post-Neutrophil Engraftment) by Month 24 |
1.0 | — |
| SECONDARY Duration of In-patient Hospitalizations (Post-Neutrophil Engraftment) up to Month 24 |
4.0 | — |
| SECONDARY Number of Intensive Care Units (ICU) Stays (Post-neutrophil Engraftment) by Month 24 |
— | — |
| SECONDARY Duration of ICU Stays (Post-neutrophil Engraftment) by Month 24 |
— | — |
| SECONDARY Number of Participants Who Tested Positive and Negative for Vector-Derived Replication Competent Lentivirus (RCL) Detected by Month 24 |
0; 35 | — |
| SECONDARY Number of Participants With Insertional Oncogenesis by Month 24 |
1 | — |
Summary
The purpose of this study is to evaluate the efficacy and safety of Lenti-D Drug Product (also known as elivaldogene autotemcel or Skysona, hereafter referred to as eli-cel) after myeloablative conditioning with busulfan and fludarabine in participants with CALD. A participant's blood stem cells will be collected and modified (transduced) using the Lenti-D lentiviral vector encoding human adrenoleukodystrophy protein. After modification (transduction) with the Lenti-D lentiviral vector, the cells will be transplanted back into the participant following myeloablative conditioning. Enrollment and treatment in Study ALD-104 have been completed and further enrollment in this study is not expected, although participants follow-up remains ongoing in the long-term follow-up Study LTF-304 (NCT02698579).
Eligibility Criteria
Inclusion Criteria
- Informed consent is 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 CALD as defined by:
- Elevated very long chain fatty acids (VLCFA) values, and
- Active central nervous system (CNS) disease established by central radiographic review of brain MRI demonstrating: i) Loes score between 0.5 and 9 (inclusive) on the 34-point scale, and ii) Gadolinium enhancement (GdE) on MRI of demyelinating lesions.
- NFS ) 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
- Baseline estimated glomerular filtration rate <70 milliliter per minute (mL/min)/1.73 square meter (m^2).
- Cardiac compromise as evidenced by left ventricular ejection fraction <40 percent (%).
- Immediate family member with a known or suspected Familial Cancer Syndrome.
- Clinically significant uncontrolled, active bacterial, viral, fungal, parasitic, or prion associated infection.
- Positive for human immunodeficiency virus type 1 or 2 (HIV-1, HIV-2); hepatitis B virus (HBV); hepatitis C virus (HCV); human T lymphotrophic virus 1 (HTLV-1). (Note that participants who have been vaccinated against HBV [positive for HBV surface antibodies] who are negative for other markers of prior HBV infection [e.g., negative for HBV core Ab] are eligible. Participants with past exposure to HBV [hepatitis B core antibody [HBcAb] -positive and/or hepatitis B e-antigen antibody [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 Ab are eligible as long as they have a negative hepatitis C viral load).
- Any clinically significant cardiovascular, hematological, 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.
- Any contraindications to the use of Granulocyte colony-stimulating factor (G-CSF) or plerixafor during the mobilization of HSCs, and any contraindications to the use of busulfan or fludarabine, including known hypersensitivity to the active substances or to any of the excipients in their formulations.
- Known hypersensitivity to protamine sulfate.
Data sourced from ClinicalTrials.gov (NCT03852498). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.