E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Childhood Cerebral Adrenoleukodystrophy (CCALD) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051260 |
E.1.2 | Term | Adrenoleukodystrophy |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• Evaluate the efficacy of Lenti-D Drug Product in subjects with CCALD. • Evaluate the safety of Lenti-D Drug Product in subjects with CCALD.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 .
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | 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). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
24 months (± 2 months) post-transplant |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints are: •Change from Baseline in Loes score •Change from Baseline in NFS. •Proportion of subjects who demonstrate resolution of gadolinium positivity on MRI (i.e. who are gadolinium negative). •Proportion of subjects who maintain an NFS less than or equal to 4 and do not increase their score by 3 points or more. •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. MFD-free survival Overall survival |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
24 months (± 2 months) post-transplant
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |