Safety and Efficacy of Olesoxime (TRO19622) in 3-25 Years SMA Patients.

Spinal Muscular Atrophy Type II Clinical Trial

Official 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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01302600
• Other study ID #: WN29836
• Secondary ID: TRO19622 CL E Q
• Status: Completed
• Phase: Phase 2
• First received: February 18, 2011
• Last updated: November 21, 2016
• Start date: November 2010
• Est. completion date: October 2013

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Institutional Ethical CommitteeFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Italy: Ethics CommitteeItaly: Ministry of HealthPoland: Ethics CommitteePoland: Ministry of HealthUnited Kingdom: Research Ethics CommitteeUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyGermany: Ethics CommissionGermany: Federal Institute for Drugs and Medical DevicesBelgium: Ethics CommitteeBelgium: Federal Agency for Medicinal Products and Health ProductsNetherlands: Medical Ethics Review Committee (METC)Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

Assess the efficacy and the safety of olesoxime in SMA type 2 or type 3 non ambulant patients aged 3-25 years

Description:

This study is a multicenter, double-blind, randomized, adaptive, parallel groups, placebo controlled 3-stage study in patients with SMA type 2 or non ambulant type 3.

Stage 1 DMC 3-month safety assessment: An independent Data Monitoring Committee (DMC)will assess the safety of olesoxime every 3 months.

Stage 2 Efficacy/futility analyses at one year: A first interim efficacy analysis will be performed after all patients have been treated for one year (52 weeks) in order to assess the need to continue the study to reach the planned objective. In the event of positive and significant results in favor of olesoxime, the study will be considered as successful and all patients will be switched to olesoxime to allow the assessment of the sustainability of the treatment effect and safety. If the results are significantly in favor of placebo, the study will be discontinued for failure (futility).

Stage 3 Efficacy and safety analysis at two years: The expected study duration is of 2 years (104 weeks) to show efficacy. If the study is not discontinued for futility or medication regimen is changed due to success, the study will therefore continue until planned completion i.e. 104 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 165
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 25 Years

Eligibility

Inclusion Criteria:

• Weakness and hypotonia consistent with a clinical diagnosis of spinal muscular atrophy (SMA) type II or III

• Laboratory documentation of homozygous absence of SMNI exon 7 and/or deletion and mutation on other allele

• MFM relative score (percentage of the maximum sum of both dimensions) >= 15% (D1 + D2 score)

• HFMS score at baseline >= 3

• Non ambulant patients defined as patients with HFMS score =< 38

• Must be 3 years of age or older, but younger than 26 years of age, at time of enrolment

• Age of onset of symptoms =< 3 years of age

• Signed informed consent of patient and/or parents/guardian

• Laboratory results drawn within 31 days prior to start of study entry demonstrating no clinically significant abnormalities

• Ability to take the study treatment (tested at screening after informed consent)

Exclusion Criteria:

• Evidence of renal dysfunction, blood dysplasia, hepatic insufficiency, symptomatic pancreatitis, congenital heart defect, known history of metabolic acidosis, hypertension,significant central nervous system impairment, or neurodegenerative or neuromuscular disease other than SMA

• Any clinically significant ECG abnormality

• 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

• 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.

• Spinal rod or fixation for scoliosis within the past 6 months or anticipated need of rod or fixation within 6 months of enrolment.

• Inability to meet study visit requirements or cooperate reliably with functional testing

• Coexisting medical conditions that contraindicate travel, testing or study medications

• Olesoxime is contraindicated in subjects/patients who develop drug hypersensitivity to it or one of the formulation excipients including hypersensitivity to sesame oil.

• Patients with hemostasis disorders

• Patients with known biliary tract obstruction

• Current or planned pregnancy or nursing period

• For Women: Failure to use one of the following safe methods of contraception:

1. Female condoms, diaphragm or coil, each used in combination with spermicides

2. Intra-uterine device

3. Hormonal contraception in combination with a mechanical method of contraception

• Participation in any other investigational drug or therapy study within the previous 3 months.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Spinal Muscular Atrophy Type II
• Spinal Muscular Atrophy Type III Non Ambulant

Intervention

Drug:
• Olesoxime
Liquid suspension formulation, 100 mg/ml at a dose of 10 mg/kg will be administered once a day with food at dinner
• Placebo
0.1ml/kg once a day with food at dinner.

Locations

Country	Name	City	State
Belgium	University Hospitals	Ghent
Belgium	University Hospitals	Leuven
France	Hôpital Femme-Mère-Enfant	Bron
France	Hôpital Raymond Poincaré	Garches
France	CHRU Hôpital R. Salengro	Lille
France	Hôpital La Timone	Marseille
France	CHU de Montpellier, Hôpital Gui de Chauliac	Montpellier
France	Groupe hospitalier Armand-Trousseau	Paris
Germany	University of Essen	Essen
Germany	Universitat Klinikum Freiburg	Freiburg
Germany	Friedrich-Baur-Institute	Munchen
Italy	Istituto Giannina Gaslini	Genova
Italy	AOU Policlinico	Messina
Italy	Centro Dino Ferrari, Milano	Milano
Italy	NEuroMuscular Omnicentre (NEMO)	Milano
Italy	Bambino Gesu' Research Children's Hospital	Roma
Italy	Policlinico Universitario "Agostino Gemelli",	Roma
Netherlands	University Medical Center	Utrecht
Poland	Medical University of Warsaw	Warsaw
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	Dubowitz Neuromuscular Centre	London
United Kingdom	Institute of Human Genetics	Newcastle

Sponsors (2)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Association Française contre les Myopathies (AFM), Paris

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Motor Function Measure	Motor function Measure (MFM) D1+D2 score	every 6 months	No
Secondary	responder analyses on MFM and HFMS, time to 4 point decrease on HFMS, CMAP/MUNE, PedsQL, FVC, CGI and safety		every 3 months	Yes