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

NCT ID: NCT01302600

Last Updated: 2016-11-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

165 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-11-30

Study Completion Date

2013-10-31

Brief Summary

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

Detailed Description

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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.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Olesoxime

100 patients in this arm. liquid suspension

Group Type EXPERIMENTAL

Olesoxime

Intervention Type DRUG

Liquid suspension formulation, 100 mg/ml at a dose of 10 mg/kg will be administered once a day with food at dinner

Placebo

50 patients enrolled in this arm. liquid suspension

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

0.1ml/kg once a day with food at dinner.

Interventions

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Olesoxime

Liquid suspension formulation, 100 mg/ml at a dose of 10 mg/kg will be administered once a day with food at dinner

Intervention Type DRUG

Placebo

0.1ml/kg once a day with food at dinner.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

3 Years

Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Association Française contre les Myopathies (AFM), Paris

OTHER

Sponsor Role collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Enrico Bertini, MD

Role: PRINCIPAL_INVESTIGATOR

Bambino Gesu Hospital

Locations

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University Hospitals

Ghent, , Belgium

Site Status

University Hospitals

Leuven, , Belgium

Site Status

Hôpital Femme-Mère-Enfant

Bron, , France

Site Status

Hôpital Raymond Poincaré

Garches, , France

Site Status

CHRU Hôpital R. Salengro

Lille, , France

Site Status

Hôpital La Timone

Marseille, , France

Site Status

CHU de Montpellier, Hôpital Gui de Chauliac

Montpellier, , France

Site Status

Groupe hospitalier Armand-Trousseau

Paris, , France

Site Status

University of Essen

Essen, , Germany

Site Status

Universitat Klinikum Freiburg

Freiburg im Breisgau, , Germany

Site Status

Friedrich-Baur-Institute

München, , Germany

Site Status

Istituto Giannina Gaslini

Genova, , Italy

Site Status

AOU Policlinico

Messina, , Italy

Site Status

Centro Dino Ferrari, Milano

Milan, , Italy

Site Status

NEuroMuscular Omnicentre (NEMO)

Milan, , Italy

Site Status

Bambino Gesu' Research Children's Hospital

Roma, , Italy

Site Status

Policlinico Universitario "Agostino Gemelli",

Roma, , Italy

Site Status

University Medical Center

Utrecht, , Netherlands

Site Status

Medical University of Warsaw

Warsaw, , Poland

Site Status

Birmingham Heartlands Hospital

Birmingham, , United Kingdom

Site Status

Dubowitz Neuromuscular Centre

London, , United Kingdom

Site Status

Institute of Human Genetics

Newcastle, , United Kingdom

Site Status

Countries

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Belgium France Germany Italy Netherlands Poland United Kingdom

References

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Bertini E, Dessaud E, Mercuri E, Muntoni F, Kirschner J, Reid C, Lusakowska A, Comi GP, Cuisset JM, Abitbol JL, Scherrer B, Ducray PS, Buchbjerg J, Vianna E, van der Pol WL, Vuillerot C, Blaettler T, Fontoura P; Olesoxime SMA Phase 2 Study Investigators. Safety and efficacy of olesoxime in patients with type 2 or non-ambulatory type 3 spinal muscular atrophy: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017 Jul;16(7):513-522. doi: 10.1016/S1474-4422(17)30085-6. Epub 2017 Apr 28.

Reference Type DERIVED
PMID: 28460889 (View on PubMed)

Other Identifiers

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TRO19622 CL E Q 1275-1

Identifier Type: OTHER

Identifier Source: secondary_id

WN29836

Identifier Type: -

Identifier Source: org_study_id