Cerebral Adrenoleukodystrophy (CALD) MedDRA version: 20.0 Level: PT Classification code 10051260 Term: Adrenoleukodystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Lenti-D Drug Product
Pharmaceutical Form: Dispersion for infusion
Other descriptive name: Autologous haematopoietic stem cells transduced with lentiviral vector Lenti-D encoding the huma
Sponsors
bluebird bio, Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Informed consent is obtained from a competent custodial parent or guardian with legal capacity to execute a local IRB/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 VLCFA values, and b. 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 on MRI of demyelinating lesions. 4. Neurologic Function Score (NFS) =1. Are the trial subjects under 18? yes Number of subjects for this age range: 20 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 ANC count 2.5 × 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 HIV, hepatitis B or C virus, or human T lymphotrophic virus 1 (HTLV-1). 12. Absence of adequate contraception for fertile subjects. 13. Any contraindications to the use of G-CSF or plerixafor during the mobilization of hematopoietic stem cells, 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy and safety of Lenti-D Drug Product after myeloablative conditioning with busulfan and fludarabine in subjects with CALD;Secondary Objective: N/A;Primary end point(s): The primary efficacy endpoint is: Proportion of subjects who are alive and have none of the 6 MFDs at Month 24 (i.e. Month 24 MFD-free survival). MFDs are: o loss of communication o cortical blindness o tube feeding o total incontinence o wheelchair dependence o complete loss of voluntary movement The primary safety endpoint is: The proportion of subjects with neutrophil engraftment after drug product infusion.;Timepoint(s) of evaluation of this end point: Month 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints are the following: • Proportion of subjects without gadolinium enhancement on MRI (i.e., GdE-) at Month 24. • Value and change in total NFS from Baseline to protocol scheduled visits. • MFD-free survival over time. • Overall survival. • Detectable vector copy number (VCN) in peripheral blood cells by Month 6. The secondary safety endpoints are the following: • The proportion of subjects who experience either acute (=Grade II) or chronic GVHD at Month 24. • Time to neutrophil engraftment after drug product infusion. • The proportion of subjects with platelet engraftment by Month 24. • Time to platelet engraftment post-drug product infusion. • The proportion of subjects with loss of neutrophil engraftment post-drug product infusion by Month 24. • The proportion of subjects who undergo a subsequent HSC infusion by Month 24. • The proportion of subjects who experience transplant-related mortality through 100 and 365 days post-drug product infusion. • The proportion of subjects who experience =Grade II acute GVHD by Month 24. • The proportion of subjects who experience chronic GVHD by Month 24. • Number of emergency room visits (post-neutrophil engraftment) by Month 24. • Number and duration of in-patient hospitalizations (post-neutrophil engraftment) by Month 24. • Number and duration of ICU stays (post-neutrophil engraftment) by Month 24. • The number of subjects in which vector-derived RCL is detected by Month 24. • The number of subjects with insertional mutagenesis leading to clonal dominance by Month 24. • The number of subjects with insertional mutagenesis leading to leukemia by Month 24.;Timepoint(s) of evaluation of this end point: Month 24 | — |
Countries
France, Germany, Italy, Netherlands, United Kingdom, United States
Contacts
Public ContactClinical Trials Operations
Voisin Consulting
Outcome results
None listed