Phase 3
N=32
A Study of the Efficacy and Safety of Hematopoietic Stem Cells Transduced With Lenti-D Lentiviral Vector for the Treatment of Cerebral Adrenoleukodystrophy (CALD)
Cerebral Adrenoleukodystrophy (CALD)
Bottom Line
View on ClinicalTrials.gov: NCT01896102 ↗Enrolled (actual)
32
Serious AEs
65.6%
Results posted
Apr 2022
Primary outcome: Primary: Percentage of Participants Who Were Alive and Have None of the 6 Major Functional Disabilities (MFDs) at Month 24 and Without Allo-HSCT or Rescue Cell Administration — 90.6 Percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Lenti-D Drug Product (eli-cel) (Genetic)
- Age
- Pediatric
- Sex
- Male
- Sponsor
- Genetix Biotherapeutics Inc.
- Primary completion
- Mar 2021
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 and Without Allo-HSCT or Rescue Cell Administration |
90.6 | — |
| PRIMARY Proportion of Participants Who Had Experienced Either Acute ([>or=] Grade II) or Chronic Graft Versus Host Disease (GVHD) by Month 24 |
0.0 | — |
| SECONDARY Percentage of Participants Who Demonstrated Resolution of Gadolinium Positivity on Magnetic Resonance Imaging (MRI) at Month 24 |
86.7 | — |
| SECONDARY Time to Sustained Resolution of Gadolinium Positivity on MRI |
77 | — |
| SECONDARY Number of Participants With Change in Total Neurologic Function Score (NFS) From Baseline up to Month 24 |
4 | — |
| SECONDARY Major Functional Disability (MFD)-Free Survival Rate |
90.6 | — |
| SECONDARY Overall Survival Rate |
96.7 | — |
| SECONDARY Proportion of Participants With Neutrophil Engraftment by 42 Days Post-drug Product Infusion |
100.0 | — |
| SECONDARY Time to Neutrophil Engraftment Post-drug Product Infusion |
13.0 | — |
| SECONDARY Proportion of Participants With Platelet Engraftment by Month 24 |
100 | — |
| SECONDARY Time to Platelet Engraftment Post-drug Product Infusion |
32 | — |
| SECONDARY Proportion of Participants With Engraftment Failure By Month 24 |
0.0 | — |
| SECONDARY Proportion of Participants Who Underwent a Subsequent Allo-Hematopoietic Stem Cell (HSC) Infusion by Month 24 |
6.5 | — |
| SECONDARY Percentage of Participants With Transplant-related Mortality Through 100 and 365 Days Post-drug Product Infusion |
0.0; 0.0 | — |
| SECONDARY Percentage of Participants With Adverse Events (AEs), Serious AEs, Grade >=3 AE, Related AEs, Related SAEs and Related Grade >=3 AEs |
100.0; 65.6; 9.4; 3.1; 93.8; 3.1 | — |
| SECONDARY Percentage of Participants With Potentially Clinical Significant Changes in Laboratory Parameters by Month 24 |
100.0; 0.0; 78.1; 43.8; 96.9; 0.0 | — |
| SECONDARY Number of Emergency Room Visits (Post-Neutrophil Engraftment) By Month 24 |
13 | — |
| SECONDARY Number of In-patient Hospitalizations (Post-Neutrophil Engraftment) By Month 24 |
14 | — |
| SECONDARY Duration of In-patient Hospitalizations (Post-Neutrophil Engraftment) up to Month 24 |
3.0 | — |
| SECONDARY Number of Intensive Care Units (ICU) Stays (Post-neutrophil Engraftment) By Month 24 |
1 | — |
| SECONDARY Duration of ICU Stays (Post-neutrophil Engraftment) By Month 24 |
12.0 | — |
| SECONDARY Number of Participants With Vector-Derived Replication Competent Lentivirus (RCL) Detected by Month 24 |
— | — |
| SECONDARY Number of Participants With Insertional Oncogenesis By Month 24 |
— | — |
Summary
This trial assessed the efficacy and safety of autologous cluster of differentiation 34 (CD34+) hematopoietic stem cells, transduced ex-vivo with Lenti-D lentiviral vector (also called elivaldogene autotemcel or eli-cel), for the treatment of cerebral adrenoleukodystrophy (CALD). A participant's blood stem cells were 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 were transplanted back into the participant following myeloablative conditioning. Participants in this study will be continuously followed in study LTF-304.
Eligibility Criteria
Inclusion Criteria
- 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 ( 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.
Data sourced from ClinicalTrials.gov (NCT01896102). 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.