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 subjects with CALD
ID
Source
Brief title
Condition
- Neurological disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the proportion of patients who are alive and have none
of the 6 major functional disabilities at Month 24 (as per protocol).
Secondary outcome
The secondary endpoints include the proportion of patients without gadolinium
enhancement at Month 24, value and change in neurological function, MFD-free
survival over time, overall survival and Detectable vector copy number in
peripheral blood cells by Month 6 (as per protocol).
Background summary
Lenti-D Drug Product has been investigated in a Phase 2/3 open-label,
single-arm study to assess efficacy and safety of Lenti-D Drug Product after
myeloablative conditioning with busulfan and cyclophosphamide (Study ALD-102;
EudraCT number: 2011-001953-10). As of January 2023, 51 subjects have been
treated with Lenti-D Drug Product in Study ALD-102 and ALD-104. Study ALD-104
is conducted to enable access to Lenti-D Drug Product upon completion of
ALD-102 enrolment and advance understanding of the suitability of alternative
conditioning regimens with Lenti-D Drug Product treatment
Study objective
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 subjects with CALD
Study design
This will be an international, non-randomized, open-label, multi-site study in
malesubjects with CALD (<=17 years of age at enrollment). Approximately 35
subjects will be infused with Lenti-D Drug Product after myeloablative
conditioning with busulfan and fludarabine.
The study has 4 distinct phases after informed consent/assent:
• Screening
• CD34+ Cell Collection, Transduction, Disposition of Lenti-D Drug Product, and
Re-confirmation of Eligibility
• Conditioning and Washout, followed by Lenti-D Drug Product Infusion on Day 1
• Maintenance (Follow-up) (Day 2 through 24 ± 1 months [Month 24])
Intervention
Lenti-D drug product infusion.
Study burden and risks
The majority of the burden and risks are those associated to the procedures
that participants will undertake.
Risks associated to the investigational procedures are the following: pain and
discomfort associated to blood sample and to potential bone marrow biopsies.
Risks associated to MRI are the following: adverse effects associated to the
contrast agents (gadolinium) and adverse effects to sedation or potential
general anaesthesia.
Additionally, there are specific potential risks associated with the gene
therapy, including the risk of cancer (e.g. myelodysplastic syndrome). Those
risks will be closely monitored during this study
This study is conducted in order to monitor the disease status of participants
and look for any side effects. It is possible that if any side effects do
occur, the monitoring patients receive while on this study will ensure they
receive proper treatment earlier than they might have otherwise.
This study may help researchers understand more fully whether gene transfer to
treat CALD is safe and effective.
Grand Union Boulevard 455
Somerville, MA 02145
US
Grand Union Boulevard 455
Somerville, MA 02145
US
Listed location countries
Age
Inclusion criteria
1. 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 subjects, in accordance with the directive of the IRB/IEC
and with local requirements.,
2. Males aged 17 years and younger, at the time of parental/guardian consent
and, where appropriate, subject assent., 3. Active cerebral ALD as defined by:,
a. Elevated very long chain fatty acids (VLCFA) values, and
b. Active central nervous system (CNS) disease established by central
radiographic review of brain magnetic resonance imaging (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.,
4. Neurologic Function Score (NFS) <=1.
Exclusion criteria
1. Prior receipt of an allogeneic transplant or gene therapy.,
2. Use of statins, Lorenzo's Oil, or dietary regimens used to lower VLCFA
levels.,
3. 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.,
4. Any conditions that make it impossible to perform MRI studies (including
allergies to anesthetics or contrast agents).,
5. Hematological compromise as evidenced by:,
a. Peripheral blood absolute neutrophil count (ANC) count <1500 cells/mm3, and
either
b. Platelet count <100,000 cells/mm3, or
c. Hemoglobin <10 g/dL.
6. Hepatic compromise as evidenced by:,
a. Aspartate transaminase (AST) value >2.5 × upper limit of normal (ULN),
b. Alanine transaminase (ALT) value >2.5 × ULN,
c. Total bilirubin value >3.0 mg/dL, except if there is a diagnosis of
Gilbert's Syndrome and the subject is otherwise stable.,
7. Baseline estimated glomerular filtration rate <70 mL/min/1.73 m2.,
8. Cardiac compromise as evidenced by left ventricular ejection fraction <40%.,
9. Immediate family member with a known or suspected Familial Cancer Syndrome.,
10. Clinically significant uncontrolled, active bacterial, viral, fungal,
parasitic, or prion associated infection.,
11. 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 subjects 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 HBVhepatitis B core antibody {HBVc Ab]}] are
eligible. Subjects with past exposure to HBV [HBcAb [HBc antibodies {Ab}
positive and/or hepatitis B e-antigen antibody {HBeAb}-positive] are also
eligible for the study provided they have a negative test for HBV
deoxyribonucleic acid [DNA.]. Also note that subjects who are positive for
anti-hepatitis C Ab are eligible as long as they have a negative hepatitis C
viral load).
12. Any clinically significant cardiovascular, haematological or pulmonary
disease, or
other disease or condition that would be contraindicated for any of the
other study procedures.
13. Absence of adequate contraception for fertile subjects. Male subjects and
their female partners are required to use two different effective methods of
contraception from Screening through at least 6 months after eli-cel 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.
14. Any contraindications to the use of G-CSF or plerixafor during the
mobilization of hematopoietic stem cells (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.
15. known hypersensitivity to protamine sulphate
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-001145-14-NL |
| ClinicalTrials.gov | NCT03852498 |
| CCMO | NL68243.000.18 |