Phase II, multicenter, randomized, adaptive, double-blind, placebo controlled study to assess safety and efficacy of olesoxime (TRO19622) in 3-25 year old Spinal Muscular Atrophy (SMA) patients.

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2010-020386-24-FR
• Date of registration: 01/06/2010
• Prospective Registration: Yes
• Primary sponsor: TROPHOS SA
• Public title: Phase II, multicenter, randomized, adaptive, double-blind, placebo controlled study to assess safety and efficacy of olesoxime (TRO19622) in 3-25 year old Spinal Muscular Atrophy (SMA) patients.
• Scientific title: Phase II, multicenter, randomized, adaptive, double-blind, placebo controlled study to assess safety and efficacy of olesoxime (TRO19622) in 3-25 year old Spinal Muscular Atrophy (SMA) patients.
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020386-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: adaptive design If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, France, Germany, Italy, Netherlands, United Kingdom

Key inclusion & exclusion criteria

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)
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 beta -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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Spinal Muscular Atrophy (type 2 or type 3 non ambulant patients aged 3-25 years)
MedDRA version: 12.1 Level: LLT Classification code 10041582 Term: Spinal muscular atrophy

Intervention(s)

Product Name: OLESOXIME
Product Code: TRO19622
Pharmaceutical Form: Oral suspension
INN or Proposed INN: olesoxime
CAS Number: 2203-87-0
Current Sponsor code: TRO19622
Other descriptive name: 4-cholesten-3-one, oxime
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Oral suspension
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary endpoint is the Motor Function Measure (MFM) D1+D2 score

Main Objective: 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

Secondary Objective: 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

Secondary ID(s)

TRO19622CLEQ1275-1