E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Spinal Muscular Atrophy - type II or III in non ambulant patients aged 3-25 years |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10032950 |
|
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 assess the efficacy and the safety of olesoxime in SMA type 2 or type 3 in non ambulant patients aged 3-25 years |
|
E.2.2 | Secondary objectives of the trial | |
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 relative score (percentage of the maximum sum of both dimensions)≥ 15% (D1 + D2) 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 then 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 parent/guardian 9.Laboratory results drawn within 31 days prior to start of study entry demonstrating no clinically significant abnormalities 10.Ability to take study treatment (tested at screening after informed consent) |
|
E.4 | Principal exclusion criteria |
1.Evidence of renal dysfunction,blood dysplasia,hepatic insufficiency,symptomatic pancreatitis,congenital heart defect,known hystory of metabolic acidosis,hypertension,significant central nervous system impairment,or neurodegenerative or neuromuscular disease other then 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 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 per example)is allowed 5.Spinal rod or fixation for scoliosis within the past 6 months or anticipated need of it 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 medication 8.Olesoxime is contraindicated in subjects who develop drug hypersensitivity to it or one of the formulaton 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 woman:failure to use one of the following safe methods of contraception-female condoms,diaphragm or coil,each used in combination with spermicides;intra-uterine device;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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is the Motor Function Measure (MFM)D1+D2 score |
|
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 |
|
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.8.3 |
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 | 4 |
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 | Information not present in EudraCT |
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
|
ultima visita dell`ultimo paziente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 |