E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
A neuromuscular, genetic disorder clinically characterized by progressive muscular weakness and atrophy |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051203 |
E.1.2 | Term | Spinal muscular atrophy congenital |
E.1.2 | System Organ Class | 100000004850 |
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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 |
• To evaluate the safety of olesoxime in patients with Spinal Muscular Atrophy (SMA) |
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E.2.2 | Secondary objectives of the trial |
• To evaluate effectiveness of olesoxime compared to the natural history of disease in patients with SMA
• To evaluate the disease associated medical complications and procedures in olesoxime treated patients compared to the natural history of disease
• To evaluate the disease course between last visit of the studies TRO19622CLEQ1275-1 and TRO19622CLEQ1115-1, and baseline assessment in this study
• To investigate the pharmacokinetics (PK) of olesoxime in the target population
• To explore changes in level of independence and health-related quality of life following treatment with olesoxime
• To assess health-related quality of life and conduct economic modeling using the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Participation in the previous studies (TRO19622CLEQ11150-1 or TRO19622CLEQ1275-1)
• Able to comply with the study protocol, in the investigator’s judgment, including ability to take study treatment and perform study visits
• For women of childbearing potential: agreement to use an acceptable birth control method during the treatment period and for at least 28 days after the last dose of olesoxime. |
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E.4 | Principal exclusion criteria |
• Patients who, in the opinion of the investigator, are not suitable to participate in this open label study
• Patients who have developed study drug hypersensitivity to olesoxime or one of the formulation excipients, including sesame oil
• Concomitant or previous participation in any other investigational drug or device study within 90 days prior to screening
• Concomitant or previous participation in a survival motor neuron protein gene (SMN2) targeting antisense oligonucleotide study within 6 months prior to screening
• Pregnant or lactating, or intending to become pregnant during the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Incidence of adverse events
2. Safety laboratory tests, Vital signs and ECG |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to 4 years
2. Up to 4 years |
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E.5.2 | Secondary end point(s) |
1. Change from baseline in Motor Function Measure (MFM) D1+D2 score and total score
2. Predose (trough) plasma olesoxime concentration at each visit
3. The Pediatric Quality of Life Inventory (PedsQL) core scales and neuromuscular sub-scales
4. The EuroQol 5-Dimension Questionnaire, 5-level version (EQ-5D-5L) score
5. SMA Independence Scale (SMAIS) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Baseline (Week 1), Week 26, Week 52, Week 78, Week 104, Week 130, thereafter every 6 months until end of study
2. Baseline (Week 1), Week 13, Week 26, Week 39, Week 52, Week 78, Week 104, Week 130, thereafter every 6 months until end of study
3. Baseline (Week 1), Week 26, Week 52, Week 78, Week 104, Week 130, thereafter every 6 months until end of study
4. Baseline (Week 1), Week 26, Week 52, Week 78, Week 104, Week 130, thereafter every 6 months until end of study
5. Baseline (week 1), week 26, week 52, week 78, week 104, week 130, thereafter every 6 months until end of study. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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) | 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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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The study will continue until olesoxime is commercially available in the patient’s country, or as per local regulation, or per the Sponsor’s decision to terminate the olesoxime program for SMA, but will not exceed 4 years after the last patient was enrolled in the study.
NB In the UK, the study will last for a fixed period of 3 years.
The end of this study is defined as the date when the last patient, last visit (LPLV) of the treatment period occurs |
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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 | |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |