The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

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




Registration number
NCT01896102
Ethics application status
Date submitted
22/03/2013
Date registered
11/07/2013
Date last updated
4/07/2019

Titles & IDs
Public 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)
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
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
Other interventions - Lenti-D Drug Product

Experimental: Lenti-D Drug Product -


Other interventions: Lenti-D Drug Product
Lenti-D Drug Product (autologous CD34+ cell-enriched population that contains cells transduced with Lenti-D lentiviral vector encoding human adrenoleukodystrophy protein, suspended in a cryopreservative solution) is administered intravenously. Lenti-D Drug Product is administered by IV infusion following myeloablative conditioning with busulfan and cyclophosphamide.

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

Outcomes
Primary outcome [1] 0 0
Proportion of subjects who are alive and have none of the 6 major functional disabilities (MFDs) at Month 24 (i.e. Month 24 MFD-free survival). - MFDs are:
loss of communication
cortical blindness
tube feeding
total incontinence
wheelchair dependence
complete loss of voluntary movement
Timepoint [1] 0 0
24 months (±1 months) post-transplant
Primary outcome [2] 0 0
The proportion of subjects who experience either acute (=Grade II) or chronic graft versus host disease (GVHD) by Month 24.
Timepoint [2] 0 0
24 months (±1 months) post-transplant
Secondary outcome [1] 0 0
Proportion of subjects who demonstrate resolution of gadolinium positivity on MRI (i.e., GdE-).
Timepoint [1] 0 0
24 months (±1 months) post-transplant
Secondary outcome [2] 0 0
Time to sustained resolution of gadolinium positivity on MRI (i.e., GdE-). - Sustained is defined as gadolinium resolution without a subsequent evaluation indicating gadolinium positivity.
Timepoint [2] 0 0
24 months (±1 months) post-transplant
Secondary outcome [3] 0 0
Change in total Neurologic Function Score (NFS) from Baseline to Month 24.
Timepoint [3] 0 0
24 months (±1 months) post-transplant
Secondary outcome [4] 0 0
MFD-free survival over time
Timepoint [4] 0 0
24 months (±1 months) post-transplant
Secondary outcome [5] 0 0
Overall survival
Timepoint [5] 0 0
24 months (±1 months) post-transplant

Eligibility
Key inclusion criteria
1. Informed consent is obtained from a competent custodial parent or guardian with legal
capacity to execute a local 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:

1. Elevated VLCFA values, and

2. Active 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 on MRI of demyelinating lesions.

4. Neurologic Function Score (NFS) = 1.
Minimum age
No limit
Maximum age
17 Years
Gender
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 VLCFA levels. Note:
subjects 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 ANC count < 1500 cells/mm3,

- Platelet count < 100,000 cells/mm3, or

- Hemoglobin < 10 g/dL.

- Uncorrected bleeding disorder.

7. Hepatic compromise as evidenced by:

- Aspartate transaminase (AST) value > 2.5×ULN

- Alanine transaminase (ALT) value > 2.5×ULN

- Total bilirubin value > 3.0 mg/dL, except if there is a diagnosis of Gilbert's
Syndrome and the subject is otherwise stable

8. Renal compromise as evidenced by abnormal renal function (actual or calculated
creatinine clearance < 50 mL/min)

9. Cardiac compromise as evidenced by left ventricular ejection fraction <40%

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 subjects 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. Subjects with past exposure to 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 subjects 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 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 drug product infusion.

15. Any contraindications to the use of 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
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/Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
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
This trial will assess the efficacy and safety of autologous CD34+ hematopoietic stem cells,
transduced ex-vivo with Lenti-D lentiviral vector, for the treatment of cerebral
adrenoleukodystrophy (CALD). A subject'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 subject following myeloablative conditioning.
Trial website
https://clinicaltrials.gov/show/NCT01896102
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Elizabeth McNeil, 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

Summary results
Other publications