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

Brief Title

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

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.

Brief Summary

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

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Motor Function Measure

Secondary Outcome

 responder analyses on MFM and HFMS, time to 4 point decrease on HFMS, CMAP/MUNE, PedsQL, FVC, CGI and safety

Condition

Spinal Muscular Atrophy Type II

Intervention

Olesoxime

Study Arms / Comparison Groups

 Olesoxime
Description:  100 patients in this arm. liquid suspension

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

165

Start Date

November 2010

Completion Date

October 2013

Primary Completion Date

October 2013

Eligibility 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.
      

Gender

All

Ages

3 Years - 25 Years

Accepts Healthy Volunteers

No

Contacts

Enrico Bertini, MD, , 

Location Countries

Belgium

Location Countries

Belgium

Administrative Informations


NCT ID

NCT01302600

Organization ID

WN29836

Secondary IDs

TRO19622 CL E Q 1275-1

Responsible Party

Sponsor

Study Sponsor

Hoffmann-La Roche

Collaborators

 Association Française contre les Myopathies (AFM), Paris

Study Sponsor

Enrico Bertini, MD, Principal Investigator, Bambino Gesu Hospital


Verification Date

November 2016