E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Spinal Muscular Atrophy (type 2 or type 3 non ambulant patients aged 3-25 years).
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E.1.1.1 | Medical condition in easily understood language |
Spinal Muscular Atrophy is a genetic disease that affects the motor neurons of the voluntary muscles that are used for activities such as crawling, walking, head and neck control, and swallowing. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10041582 |
E.1.2 | Term | Spinal muscular atrophy |
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 |
The main objectif is to assess the efficacy of olesoxime in SMA type 2 or type 3 non ambulant patients aged 3-25 years .
The primary outcome measure is the Motor Function Measure (MFM) D1and D2 score |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives measures will be responder analyses on MFM and HFMS , time to 4 point decrease on HFMS,CMAP/MUNE,PedsQL,FVC,CGI and safety |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Weakness and hypotonia consistent with a clinical diagnosis of spinal muscular atrophy(SMA) type II or III
2. Laboratory documentation of homozygous absence of SMNI exon 7 and/or deletion
and mutation on other allele
3. MFM score ≥15% (D1 + D2 score)
4. HFMS score at baseline ≥ 3
5. Non ambulant patients defined as patients with HFMS score ≤ 38
6. Must be 3 years of age or older, but younger than 26 years of age, at time of enrolment
7. Age of onset of symptoms ≤ 3 years of age
8. Signed informed consent of patient and/or parents/guardian
9. Laboratory results drawn within 31 days prior to start of study entry demonstrating no clinically significant abnormalities
10. Ability to take the study treatment (tested at screening after informed consent) |
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E.4 | Principal exclusion criteria |
Subjects who meet one or more of the following criteria are not allowed to be included in the study:
1. Evidence of renal dysfunction, blood dysplasia, hepatic insufficiency, symptomatic
pancreatitis, cardiac arrhythmia, congenital heart defect, known history of metabolic
acidosis, hypertension, significant central nervous system impairment, or neurodegenerative or neuromuscular disease other than SMA
2. Any clinically significant ECG abnormality
3. Any acute co-morbid condition interfering with the well-being of the subject within 7 days of enrolment including bacterial infection, viral infectious processes, food poisoning, temperature > 37.0 °C, the need for acute treatment or observation due to any other reason, as judged by the investigator; patient can be included after resolution of the acute event
4. Use of medications intended for the treatment of SMA including riluzole, valproic
acid, hydroxyurea, sodium phenylbutyrate, butyrate derivatives, creatine, carnitine,
growth hormone, anabolic steroids, probenecid, oral or parenteral use of corticosteroids at entry, agents anticipated to increase or decrease muscle strength or agents with known or presumed histone deacetylase (HDAC) inhibition, within 30 days prior to study entry. Subjects who use a nebulizer or require an inhaler to steroids will be allowed in the study; however oral use of steroids is prohibited.
The oral use of salbutamol is permitted with the following restrictions: patients should have been on salbutamol for at least 6 months before inclusion in the trial, with good tolerance. The dose of salbutamol should remain constant for the duration of the trial. The use of inhaled β-agonists (for the treatment of asthma crisis for example) is allowed.
5. Spinal rod or fixation for scoliosis within the past 6 months or anticipated need of rod or fixation within 6 months of enrolment.
6. Inability to meet study visit requirements or cooperate reliably with functional testing
7. Coexisting medical conditions that contraindicate travel, testing or study medications
8. Olesoxime is contraindicated in subjects/patients who develop drug hypersensitivity to it or one of the formulation excipients including hypersensitivity to sesame oil.
9. Patients with hemostasis disorders
10. Patients with known biliary tract obstruction
11. Current or planned pregnancy or nursing period
12. For Women: Failure to use one of the following safe methods of contraception:
a) Female condoms, diaphragm or coil, each used in combination with spermicides
b) Intra-uterine device
c) Hormonal contraception in combination with a mechanical method of contraception
13. Participation in any other investigational drug or therapy study within the previous 3 months. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the Motor Function Measure (MFM) D1+D2 score |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
MFM is evaluated at Day 0, 6 months, 12 months, 1 year, 18 months and 2 years |
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E.5.2 | Secondary end point(s) |
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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 | 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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
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 | 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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End of the trial: last visit for last patient.
A first interim efficacy analysis will be performed after 1 year treatment of all patients to assess the need to continue the study. If the results are positive and significant in favour of olesoxime, all patients will be switched to olesoxime to allow the assessment of efficacy and safety of the treatment. If the results are significantly in favour of placebo, the study will be discontinued for failure (futility).
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 30 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 30 |
E.8.9.2 | In all countries concerned by the trial days | 0 |