Clinical trial NCT02628743: A Study to Evaluate Long Term Safety, Tolerability, and Effectiveness of Olesoxime in Patients With Spinal Muscular Atrophy (SMA)
Official title: Multicenter, Open-Label, Single-Arm Study to Evaluate Long-Term Safety, Tolerability, and Effectiveness of 10 mg/kg BID Olesoxime in Patients With Spinal Muscular Atrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Muscular Atrophy, Spinal
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-12-11
Enrollment: 131
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this open-label, single arm study is to further evaluate long-term tolerability, safety and efficacy outcomes of olesoxime in participants with Spinal Muscular Atrophy (SMA) who previously participated in one of the following two clinical studies: TRO19622 CL E Q 1115-1 (open-label Phase Ib, multicenter, single- and multiple- dose study) or TRO19622 CL E Q 1275-1 (NCT01302600, Phase II/III, adaptive, parallel-group, double blind, randomized, placebo-controlled, multicenter, multinational study).


Eligibility criteria: Inclusion Criteria:

* Participation in the previous studies (TRO19622 CL E Q 1115-1 or TRO19622 CL E Q 1275-1)
* For women of childbearing potential: agreement to use an acceptable birth control method during the treatment period and for at least 28 days after the last dose of olesoxime

Exclusion Criteria:

* Female participants who are pregnant or lactating, or intending to become pregnant during the study
* Participants who, in the opinion of the investigator, are not suitable to participate in this open-label study
* Participants who have developed study drug hypersensitivity to olesoxime or one of the formulation excipients, including sesame oil
* Concomitant or previous participation in any investigational drug or device study within 90 days prior to screening
* Concomitant or previous participation in a survival motor neuron 2 (SMN2) targeting antisense oligonucleotide study within 6 months prior to screening
* History of human immunodeficiency virus infection, history of Hepatitis B infection within the past year, history of Hepatitis C infection which has not been adequately treated
* History of illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment
* Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study
* History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion

Primary outcomes:
measure: Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: Baseline up to approximately 3 years
Secondary outcomes:
measure: Change From Baseline in Motor Function Measure (MFM) Dimension 1 (D1) + Dimension 2 (D2) Score
timeFrame: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
measure: Change From Baseline in MFM Total Score (D1+ D2 + Dimension 3 [D3]) Score
timeFrame: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
measure: Plasma Concentrations of Olesoxime
timeFrame: Pre-dose (Hour 0) at Weeks 1, 13, 26, 39, 52, 78, 104 and 130
measure: Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score
timeFrame: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
measure: Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score
timeFrame: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
measure: Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score
timeFrame: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
measure: Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score
timeFrame: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
measure: Change From Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire Index Score - Total Score
timeFrame: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
measure: Change From Baseline in Caregiver Proxy EQ-5D-5L Questionnaire Index Score - Total Score
timeFrame: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
measure: Change From Baseline in EQ-5D-5L Visual Analogue Scale (EQ-5D-5L VAS) Score
timeFrame: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
measure: Change From Baseline in Caregiver Proxy EQ-5D-5L VAS Score
timeFrame: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
measure: Number of Subjects Employed Assessed Using the Work Productivity and Activity Impairment Questionnaire: Caregiver (WPAI:CG) Questionnaire
timeFrame: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
measure: Change From Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire
timeFrame: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
measure: Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score
timeFrame: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
measure: Change From Baseline in Degree Patient Caregiving Affected Productivity and Activities Using WPAI:CG Questionnaire
timeFrame: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
measure: Change From Baseline in Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS): Caregiver
timeFrame: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
measure: Change From Baseline in SF-36 Domain Scores: Caregiver
timeFrame: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
measure: Change From Baseline in Revised Utility Index Score (SF-6D_R2): Caregiver
timeFrame: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
measure: SMA Independence Scale (SMAIS) Score: Patient
timeFrame: Week 104 and Week 130
measure: SMA Independence Scale (SMAIS) Score: Caregiver
timeFrame: Week 104 and Week 130
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Bron
country: France
facility: Hopital Femme Mere Enfant; Medecine Physique et Readaptation Pediatrique - L'ESCALE
city: Garches
country: France
facility: Hôpital Raymond Poincare; Serv. Neurologie et Réanimation pédiatriques - Centre réf. neuromusculaire
city: Lille
country: France
facility: Hopital Jeanne De Flandre; CIC pediatrique
city: Marseille
country: France
facility: Hopital la Timone Enfants; Service de Pediatrie et Neurologie Pediatrique
city: Montpellier
country: France
facility: CHRU de Montpellier, Hopital Gui de Chauliac; Service de Neuropediatrie
city: Paris Cedex 12
country: France
facility: Hopital Armand Trousseau; centre reference Maladies Neuro-musculaires Est parisien Neuropediatrie
city: Toulouse
country: France
facility: Hopital des Enfants; Unite de Neurologie Pediatrique
city: Essen
country: Germany
facility: Universitätsklinikum Essen; Neuropädiatrie
city: Freiburg
country: Germany
facility: Uniklinikum Freiburg Zentrum für Kinder- und Jugendmedizin; Neuropädiatrie und Muskelerkrankungen
city: München
country: Germany
facility: Dr. Von Haunersches Kinderspital
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesù; Dip. Neuroscienze e Salute Mentale
state: Lazio
city: Roma
country: Italy
facility: Policlinico Agostino Gemelli; Dipartimento di Neuropsichiatria Infantile
state: Lazio
city: Genova
country: Italy
facility: IRCCS Istituto G. Gaslini; UOC Neurologia Pediatrica e Malattie Muscolari
state: Liguria
city: Milano
country: Italy
facility: I.R.C.C.S. Cà Granda - Ospedale Maggiore Policlinico; Dip. di Salute Mentale
state: Lombardia
city: Milano
country: Italy
facility: ASST GRANDE OSPEDALE METROPOLITANO NIGUARDA;NEMO (NEuroMuscular Omnicentre);Centro clinico - Fonda
state: Lombardia
city: Messina
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico G.Martino; Dip. Neurologia e Malattie neuromuscolari
state: Sicilia
city: Utrecht
country: Netherlands
facility: UMC Utrecht; Polkliniek Neuromusculaire ziekten
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie; Klinika Neurologii
city: Birmingham
country: United Kingdom
facility: Heart of England NHS Trust
city: London
country: United Kingdom
facility: National Hospital for Neurology and Neurosurgery,; MRC Centre for Neuromuscular Diseases
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle University & The Newcastle upon Tyne Hospitals NHS Foundation Trust
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: