Clinical study to assess the efficacy and safety of gene therapy for the treatment of childhood cerebral adrenoleukodystrophy

Phase 1

• Conditions: Childhood Cerebral Adrenoleukodystrophy (CCALD); MedDRA version: 18.0Level: PTClassification code 10051260Term: AdrenoleukodystrophySystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2011-001953-10-FR
• Lead Sponsor: bluebird bio, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-06-24
• Last Update Posted: 10 May 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 15

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.Boys 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 plasma VLCFA levels, and
b.Active 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.NFS = 1 .

Are the trial subjects under 18? yes
Number of subjects for this age range: 15
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

1.Receipt of an allogeneic transplant or gene therapy.
2.Availability of a willing 10/10 HLA-matched sibling donor (excluding female heterozygote).
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 counfound 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:
a.Peripheral blood absolute neutrophil count (ANC) < 1500 cells/mm3,
b.Platelet count < 100,000 cells/mm3, or
c.Hemoglobin < 10 g/dL.
d.Uncorrected bleeding disorder.
7.Hepatic compromise as evidenced by:
a.Aspartate transaminase (AST) value > 2.5× the upper limit of normal (ULN) or
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
8.Renal compromise as evidenced by:
a.Abnormal renal function (creatinine clearance < 50 mL/min)
9.Cardiac compromise as evidenced by:
a.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 syndrome, and familial adenomatous polyposis).
11.Clinically significant active bacterial, viral, fungal, or parasitic or prion assiociated infections.
12.Positive for presence of human immunodeficiency virus type 1 or 2 (HIV 1, HIV 2), hepatitis B, hepatitis C, or 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] are eligible. 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 by quantitative polymerase chain reaction [qPCR].)
13.Any clinically significant cardiovascular or pulmonary, or other disease or condition that would be contraindicated for any of the other study procedures.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: • Evaluate the efficacy of Lenti-D Drug Product in subjects with CCALD.<br>• Evaluate the safety of Lenti-D Drug Product in subjects with CCALD.<br>;Secondary Objective: Not Applicable;Primary end point(s): Assessment of the proportion of subjects who have no Major Functional Disabilities (MFDs) as determined by key measures in the Neurological Function Score (NFS). ;Timepoint(s) of evaluation of this end point: 24 months (± 2 months) post-transplant

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: 24 months (± 2 months) post-transplant<br>;Secondary end point(s): Secondary efficacy endpoints are:<br>•Change from Baseline in Loes score<br>•Change from Baseline in NFS. <br>•Proportion of subjects who demonstrate resolution of gadolinium positivity on MRI (i.e. who are gadolinium negative).<br>•Proportion of subjects who maintain an NFS less than or equal to 4 and do not increase their score by 3 points or more.<br>•Proportion of subjects who maintain a Loes score less than or equal to 9 or do not increase their score by 6 points or more.<br>MFD-free survival<br>Overall survival