E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cerebral Adrenoleukodystrophy (CALD) |
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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 | 20.0 |
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 |
-Monitor for longterm safety of the Lenti-D Drug Product administered in clinical Study ALD-102 -Monitor for longterm efficacy of Lenti-D Drug Product |
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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. Provision of written informed consent for this study by the subject or subject’s parent(s)/ legal guardian(s) and written informed assent by subject, if applicable 2. Have received Lenti-D Drug Product in Study ALD-102 3. Able to comply with study requirements |
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E.4 | Principal exclusion criteria |
1. Met the VCN discontinuation criterion from Study ALD-102, as follows: the subject has undetectable VCN (<0.0003 copies per cell) in peripheral blood cells for 2 consecutive measurements at least 1 month apart and at least 12 months after drug product infusion.
This exclusion criterion does not apply to subjects who received allo-HSCT after Lenti-D Drug Product infusion in Study ALD-102 |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Safety Endpoints include: - Overall survival - Proportion of subjects who experience new, persistent or worsening chronic GVHD - Proportion of subjects who undergo subsequent stem cell transplantation - All drug product-related AEs through 15 years post-drug product infusion - All SAEs through 15 years post-drug-product infusion (regardless of relatedness to drug product), including any new malignancy or new diagnosis of a neurologic, rheumatologic, or hematologic disorder that, in the Investigator’s opinion, is clinically significant and requires medical intervention; SAEs related to drug product would be collected through 15 years post-drug-product infusion - Incidence of vector-derived RCL, assessed from archived samples as clinically indicated. - Characterization of events of insertional mutagenesis leading to clonal dominance or leukemia - Laboratory tests as specified
2. Efficacy Endpoints include: -MFD-free survival
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Visits are scheduled every 6 months for years 2 to 5 post-drug-product infusion and then annually through 15 years post-drug-product infusion |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints include the following: - Change from Baseline (defined in parent study) in Loes score - Change from Baseline (defined in parent study) in NFS - Proportion of subjects who remain gadolinium enhancement (GdE)-negative on MRI of those who were GdE-negative at entry of LTF-304, and proportion of subjects who become and remain GdE-negative on MRI of those who were GdE-positive at entry of LTF-304 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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) | No |
E.7.1.1 | First administration to humans | No |
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) | No |
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 | No |
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 |
Algeria |
Argentina |
Australia |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 15 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 15 |