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

This study has been completed.
Sponsor:
Collaborator:
Association Française contre les Myopathies (AFM), Paris
Information provided by (Responsible Party):
Trophos
ClinicalTrials.gov Identifier:
NCT01302600
First received: February 18, 2011
Last updated: October 18, 2013
Last verified: October 2013
  Purpose

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


Condition Intervention Phase
Spinal Muscular Atrophy Type II
Spinal Muscular Atrophy Type III Non Ambulant
Drug: Olesoxime
Drug: Placebo
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Trophos:

Primary Outcome Measures:
  • Motor Function Measure [ Time Frame: every 6 months ] [ Designated as safety issue: No ]
    Motor function Measure (MFM) D1+D2 score


Secondary Outcome Measures:
  • responder analyses on MFM and HFMS, time to 4 point decrease on HFMS, CMAP/MUNE, PedsQL, FVC, CGI and safety [ Time Frame: every 3 months ] [ Designated as safety issue: Yes ]

Enrollment: 165
Study Start Date: November 2010
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Olesoxime
100 patients in this arm. liquid suspension
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 Comparator: Placebo
50 patients enrolled in this arm. liquid suspension
Drug: Placebo
0.1ml/kg once a day with food at dinner.

Detailed 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.

  Eligibility

Ages Eligible for Study:   3 Years to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01302600

Locations
Belgium
University Hospitals
Ghent, Belgium, 9000
University Hospitals
Leuven, Belgium, 3000
France
Hôpital Femme-Mère-Enfant
Bron, France, 69677
Hôpital Raymond Poincaré
Garches, France, 92380
CHRU Hôpital R. Salengro
Lille, France, 59037
Hôpital La Timone
Marseille, France, 13385
CHU de Montpellier, Hôpital Gui de Chauliac
Montpellier, France, 34295
Groupe hospitalier Armand-Trousseau
Paris, France, 75012
Germany
University of Essen
Essen, Germany, 45122
Universitat Klinikum Freiburg
Freiburg, Germany, 79106
Friedrich-Baur-Institute
Munchen, Germany, 80336
Italy
Istituto Giannina Gaslini
Genova, Italy, 16147
AOU Policlinico
Messina, Italy, 98 125
Centro Dino Ferrari, Milano
Milano, Italy, 20122
NEuroMuscular Omnicentre (NEMO)
Milano, Italy, 20162
Bambino Gesu' Research Children's Hospital
Roma, Italy, 165
Policlinico Universitario "Agostino Gemelli",
Roma, Italy, 168
Netherlands
University Medical Center
Utrecht, Netherlands, 3508 GA
Poland
Medical University of Warsaw
Warsaw, Poland, 02-097
United Kingdom
Birmingham Heartlands Hospital
Birmingham, United Kingdom, B92 0AN
Dubowitz Neuromuscular Centre
London, United Kingdom, WC1N 1EH
Institute of Human Genetics
Newcastle, United Kingdom, NE1 3BZ
Sponsors and Collaborators
Trophos
Association Française contre les Myopathies (AFM), Paris
Investigators
Principal Investigator: Enrico Bertini, MD Bambino Gesu Hospital
  More Information

No publications provided

Responsible Party: Trophos
ClinicalTrials.gov Identifier: NCT01302600     History of Changes
Other Study ID Numbers: TRO19622 CL E Q 1275-1
Study First Received: February 18, 2011
Last Updated: October 18, 2013
Health Authority: France: Institutional Ethical Committee
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: Ethics Committee
Italy: Ministry of Health
Poland: Ethics Committee
Poland: Ministry of Health
United Kingdom: Research Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Belgium: Ethics Committee
Belgium: Federal Agency for Medicinal Products and Health Products
Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:
Muscular Atrophy
Muscular Atrophy, Spinal
Spinal Muscular Atrophies of Childhood
Atrophy
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Pathological Conditions, Anatomical
Signs and Symptoms
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases
Heredodegenerative Disorders, Nervous System
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on August 28, 2014