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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01896102




Registration number
NCT01896102
Ethics application status
Date submitted
22/03/2013
Date registered
11/07/2013

Titles & IDs
Public title
A Study of the Efficacy and Safety of Hematopoietic Stem Cells Transduced With Lenti-D Lentiviral Vector for the Treatment of Cerebral Adrenoleukodystrophy (CALD)
Scientific title
A Phase 2/3 Study of the Efficacy and Safety of Hematopoietic Stem Cells Transduced With Lenti-D Lentiviral Vector for the Treatment of Cerebral Adrenoleukodystrophy (CALD)
Secondary ID [1] 0 0
2011-001953-10
Secondary ID [2] 0 0
ALD-102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cerebral Adrenoleukodystrophy (CALD) 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Other neurological disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Lenti-D Drug Product (eli-cel)

Experimental: Lenti-D Drug Product - Participants received a single intravenous (IV) infusion of Lenti-D Drug Product at a dose of greater than or equal to (\>=) 5.0 × 10\^6 CD34+ cells/kilogram (kg) (autologous CD34+ cell-enriched population that contained cells transduced with lentiviral vector encoding ABCD1 cDNA for human adrenoleukodystrophy protein, suspended in a cryopreservative solution) on Day 0.


Treatment: Other: Lenti-D Drug Product (eli-cel)
Participants received a single IV infusion of Lenti-D Drug Product.

Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
At Month 24
Primary outcome [2] 0 0
Proportion of Participants Who Had Experienced Either Acute ([>or=] Grade II) or Chronic Graft Versus Host Disease (GVHD) by Month 24
Timepoint [2] 0 0
By Month 24
Secondary outcome [1] 0 0
Percentage of Participants Who Demonstrated Resolution of Gadolinium Positivity on Magnetic Resonance Imaging (MRI) at Month 24
Timepoint [1] 0 0
At Month 24
Secondary outcome [2] 0 0
Time to Sustained Resolution of Gadolinium Positivity on MRI
Timepoint [2] 0 0
Up to Month 24
Secondary outcome [3] 0 0
Number of Participants With Change in Total Neurologic Function Score (NFS) From Baseline up to Month 24
Timepoint [3] 0 0
Baseline up to Month 24
Secondary outcome [4] 0 0
Major Functional Disability (MFD)-Free Survival Rate
Timepoint [4] 0 0
At 24 months after Lenti-D drug infusion
Secondary outcome [5] 0 0
Overall Survival Rate
Timepoint [5] 0 0
At 24 months after Lenti-D drug infusion
Secondary outcome [6] 0 0
Proportion of Participants With Neutrophil Engraftment by 42 Days Post-drug Product Infusion
Timepoint [6] 0 0
By 42 days post-drug infusion
Secondary outcome [7] 0 0
Time to Neutrophil Engraftment Post-drug Product Infusion
Timepoint [7] 0 0
By 42 days post-drug infusion
Secondary outcome [8] 0 0
Proportion of Participants With Platelet Engraftment by Month 24
Timepoint [8] 0 0
By Month 24
Secondary outcome [9] 0 0
Time to Platelet Engraftment Post-drug Product Infusion
Timepoint [9] 0 0
By Month 24
Secondary outcome [10] 0 0
Proportion of Participants With Engraftment Failure By Month 24
Timepoint [10] 0 0
By Month 24
Secondary outcome [11] 0 0
Proportion of Participants Who Underwent a Subsequent Allo-Hematopoietic Stem Cell (HSC) Infusion by Month 24
Timepoint [11] 0 0
By Month 24
Secondary outcome [12] 0 0
Percentage of Participants With Transplant-related Mortality Through 100 and 365 Days Post-drug Product Infusion
Timepoint [12] 0 0
From time of drug product infusion through 100 and 365 days post-drug product infusion
Secondary outcome [13] 0 0
Percentage of Participants With Adverse Events (AEs), Serious AEs, Grade >=3 AE, Related AEs, Related SAEs and Related Grade >=3 AEs
Timepoint [13] 0 0
From date of informed consent up to Month 24
Secondary outcome [14] 0 0
Percentage of Participants With Potentially Clinical Significant Changes in Laboratory Parameters by Month 24
Timepoint [14] 0 0
From time of drug product infusion up to Month 24
Secondary outcome [15] 0 0
Number of Emergency Room Visits (Post-Neutrophil Engraftment) By Month 24
Timepoint [15] 0 0
From Post-Neutrophil Engraftment up to Month 24
Secondary outcome [16] 0 0
Number of In-patient Hospitalizations (Post-Neutrophil Engraftment) By Month 24
Timepoint [16] 0 0
From post-neutrophil engraftment up to Month 24
Secondary outcome [17] 0 0
Duration of In-patient Hospitalizations (Post-Neutrophil Engraftment) up to Month 24
Timepoint [17] 0 0
From post-neutrophil engraftment up to Month 24
Secondary outcome [18] 0 0
Number of Intensive Care Units (ICU) Stays (Post-neutrophil Engraftment) By Month 24
Timepoint [18] 0 0
From post-neutrophil engraftment up to Month 24
Secondary outcome [19] 0 0
Duration of ICU Stays (Post-neutrophil Engraftment) By Month 24
Timepoint [19] 0 0
From post-neutrophil engraftment up to Month 24
Secondary outcome [20] 0 0
Number of Participants With Vector-Derived Replication Competent Lentivirus (RCL) Detected by Month 24
Timepoint [20] 0 0
By Month 24
Secondary outcome [21] 0 0
Number of Participants With Insertional Oncogenesis By Month 24
Timepoint [21] 0 0
By Month 24

Eligibility
Key inclusion criteria
1. 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).
2. Males aged 17 years and younger, at the time of parental/guardian consent and, where appropriate, participant assent.
3. Active cerebral adrenoleukodystrophy (ALD) as defined by:

1. Elevated very long chain fatty acids (VLCFA) values, and
2. Active CNS disease established by central radiographic review of brain magnetic resonance imaging (MRI) demonstrating:
3. Loes score between 0.5 and 9 (inclusive) on the 34-point scale, and
4. Gadolinium enhancement on MRI of demyelinating lesions.
4. NFS less than or equal to (<or=) 1.
Minimum age
No limit
Maximum age
17 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Receipt of an allogeneic transplant or gene therapy.
2. Availability of a willing 10/10 HLA-matched sibling donor (excluding female heterozygotes).
3. 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.
4. 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.
5. Any conditions that make it impossible to perform MRI studies (including allergies to anesthetics or contrast agents).
6. 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.
7. 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
8. Renal compromise as evidenced by abnormal renal function (actual or calculated creatinine clearance < 50 milliliter per minute [mL/min])
9. Cardiac compromise as evidenced by left ventricular ejection fraction <40 percent (%)
10. 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).
11. Clinically significant active bacterial, viral, fungal, parasitic, or prion-associated infection
12. 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.
13. Any clinically significant cardiovascular or pulmonary disease, or other disease or condition that would be contraindicated for any of the other study procedures.
14. 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.
15. 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Women and Children's Hospital - North Adelaide
Recruitment postcode(s) [1] 0 0
5006 - North Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
Minnesota
Country [4] 0 0
Argentina
State/province [4] 0 0
Buenos Aires
Country [5] 0 0
France
State/province [5] 0 0
Le Kremlin-Bicêtre Cedex
Country [6] 0 0
Germany
State/province [6] 0 0
Leipzig
Country [7] 0 0
United Kingdom
State/province [7] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
bluebird bio
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jakob Sieker, MD.
Address 0 0
bluebird bio, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Bluebird bio is committed to transparency and appropriately de-identified patient-level datasets and supporting documents may be shared following attainment of applicable marketing approvals associated with this study and consistent with criteria established by bluebird bio and/or industry best practices to maintain the privacy of study participants. Note that given the rarity of the disease and the identifiable nature of the participants in this study, it is anticipated that the sharing of data from this study may be limited. For enquiries, please contact us at [email protected].
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.