Phase 3 Efficacy and Safety Study of BG00012 in Pediatric Subjects With Relapsing-remitting Multiple Sclerosis (RRMS)
- Conditions
- Relapsing-Remitting Multiple Sclerosis
- Interventions
- Drug: Interferon β-1a
- Registration Number
- NCT02283853
- Lead Sponsor
- Biogen
- Brief Summary
The main objectives of Part 1 are as follows: To evaluate the safety, tolerability, and efficacy of BG00012 in pediatric subjects with RRMS, as compared with a disease-modifying treatment and to assess health outcomes and evolution of disability. The primary objective of Part 2 is to evaluate the long-term safety of BG00012 in subjects who completed Week 96 in Part 1 of Study 109MS306. The secondary objective of Part 2 is to describe the long-term MS outcomes of BG00012 in subjects who completed Week 96 in Part 1 of Study 109MS306.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 156
- Must have a body weight of ≥30 kg.
- Must have a diagnosis of RRMS (consensus definition for pediatric RRMS [Krupp 2007]).
- Must be ambulatory with a baseline EDSS score between 0 and 5.5, inclusive.
- Must have experienced at least 1 of the following 3 conditions: a) at least 1 relapse within the last 12 months prior to Day 1 with a prior brain MRI demonstrating lesions consistent with MS; b) at least 2 relapses within the last 24 months prior to Day 1, with a prior brain MRI demonstrating lesions consistent with MS; c) evidence of Gd-enhancing lesions of the brain on an MRI performed within the 6 weeks prior to Day 1.
- Must be neurologically stable, with no evidence of relapse within 50 days prior to Day 1 and no evidence of corticosteroid treatment within 30 days prior to Day 1.
- Subjects of childbearing potential who are sexually active must be willing to practice effective contraception during the study and be willing and able to continue contraception for at least 30 days after their final dose of study treatment.
Key
-
Primary progressive, secondary progressive, or progressive relapsing MS (as defined by [Lublin and Reingold 1996]). These conditions require the presence of continuous clinical disease worsening over a period of at least 3 months. Subjects with these conditions may also have superimposed relapses but are distinguished from relapsing-remitting subjects by the lack of clinically stable periods or clinical improvement.
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Disorders mimicking MS, such as other demyelinating disorders (e.g., acute disseminated encephalomyelitis), systemic autoimmune disorders (e.g., Sjögren disease, lupus erythematosus), metabolic disorders (e.g., dystrophies), and infectious disorders.
-
History of premalignant or malignant disease. Subjects with basal cell carcinoma that has been completely excised prior to screening will remain eligible.
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History of severe allergic or anaphylactic reactions, or known drug hypersensitivity to DMF, fumaric acid esters, or interferon beta-1a (IFN Beta-1a).
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History of abnormal laboratory results indicative of any significant endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, renal, and/or any other major disease that would preclude participation in a clinical study.
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History of clinically significant cardiovascular, pulmonary, GI, dermatologic, growth, developmental, psychiatric (including depression), neurologic (other than MS), and/or other major disease that would preclude participation in a clinical study.
-.History of human immunodeficiency virus.
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An MS relapse that has occurred within 50 days prior to Day 1 AND/OR the subject has not stabilized from a previous relapse prior to Day 1.
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Other unspecified reasons that, in the opinion of the Investigator or Biogen Idec, make the subject unsuitable for enrollment.
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For the PD/PK subset of subjects: subjects unable to swallow the BG00012 capsule whole.
Key Treatment history
- Any previous treatment with Fumaderm (fumaric acid esters) or BG00012.
- Prior treatment with any of the following: total lymphoid irradiation, cladribine, T-cell or T-cell receptor vaccination, any therapeutic monoclonal antibody, with the exception of rituximab or natalizumab.
- Prior treatment with any of the following medications within the 12 months prior to Day 1: mitoxantrone, cyclophosphamide, rituximab.
- Prior treatment with any of the following medications or procedures within 6 months prior to Day 1: fingolimod; teriflunomide; natalizumab; cyclosporine; azathioprine; methotrexate; mycophenolate mofetil; laquinimod; intravenous (IV) immunoglobulin; plasmapheresis or cytapheresis
- Treatment with any of the following medications within 30 days prior to Day 1: steroids (IV or oral corticosteroid treatment, including agents that may not act through the corticosteroid pathway [e.g.low dose naltrexone]), 4-aminopyridine or related products (except subjects on a stable dose of controlled-release fampridine for 3 months)
NOTE: Other protocol-defined inclusion/exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description IFN β-1a (Avonex) Interferon β-1a Participants will receive the recommended dose of 30 μg (weekly) BG00012 dimethyl fumarate Participants will receive the recommended dose of 240 mg orally, twice a day
- Primary Outcome Measures
Name Time Method Number of Participants That Experience Adverse Events (AEs) or Serious Adverse Events (SAEs) Up to 7 years Part 2 will be an optional open-label extension phase in subjects who complete Part 1 and who meet the Part 2 entry criteria.
Proportion of Participants Free of New/Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans At week 96 Part 1
Number of Participants Who Discontinue Study Treatment due to an AE Up to 7 years Part 2
- Secondary Outcome Measures
Name Time Method The Number of New/Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans At Week 24 and Week 96 Part 1
Quality of Life as measured by the PedsQL Up to Week 96 Part 1
Proportion of Participants Free of New/Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans At Week 24 and Week 48 Part 1
Proportion of Participants Free of New MRI Activity as measured by Brain MRI Scans At Weeks 24, 48 and 96 Part 1. New MRI Activitiy includes: Gd-enhancing MRI lesions on brain MRI scans; New T2 MRI lesions on brain MRI scans and newly enlarging MRI lesions on brain MRI scans
Time to First Relapse Up to Week 96 Part 1
Proportion of Participants Who Do Not Experience Relapse Up to Week 96 Part 1
Annualized Relapse Rate Up to 7 years Part 2
Number of Participants That Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) Up to Week 96 Part 1. Including prospective and follow-up of flushing, nausea, abdominal pain and diarrhea
Change from Baseline to Week 96 in the Expanded Disability Status Scale (EDSS) Score Up to Week 96 Part 1. The EDSS measures the disability status of people with multiple sclerosis on a scale that ranges from 0 to 10. The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refer to the loss of ambulatory ability. The range of main categories include (0) = normal neurologic exam; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death due to MS.
Vital Signs, Electrocardiograms (ECGs) and Changes in Clinical Laboratory Data, including Monitoring of Liver Function, Renal Function, Hematologic, and Coagulation Parameters Up to Week 96 Part 1
Fatigue as measured by the Pediatric Quality of Life Inventory (PedsQL) Multidimensional Fatigue Scale Scores Up to Week 96 Part 1. Multidimensional Fatigue Scale scores - designed as a generic symptom-specific instrument to measure fatigue in patients with acute and chronic health conditions as well as healthy school and community populations.
Change from Baseline in School Progression Query Up to 7 years Part 2. If permitted by the local regulatory authority, participants or caregivers will be posed the following question: "During the past year, did \[you/the subject\] progress from one \[class/grade-level\] to the next in school?"
Number of Participants with Incidences of Clinically Relevant Laboratory Assessment Abnormalities Up to 7 years Part 2
Change from Baseline in Bone Age Up to 7 years Part 2
Number of Participants with Incidences of Clinically Relevant ECG Abnormalities Up to 7 years Part 2
Change from Baseline in EDSS Score Up to 7 years Part 2. The EDSS measures the disability status of people with multiple sclerosis on a scale that ranges from 0 to 10. The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refer to the loss of ambulatory ability. The range of main categories include (0) = normal neurologic exam; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death due to MS.
Change from Baseline in Symbol Digit Modalities Test (SDMT) Score Up to 7 years Part 2. SDMT is used to assess processing speed. Participants are given 90 seconds in which to pair specific numbers with given geometric figures using a key. The score is number of correctly coded items from 0 (worst) to 110 (best). Higher scores indicate better performance.
Number of Participants with Incidences of Clinically Relevant Vital Signs Abnormalities Up to 7 years Part 2
Change from Baseline in Brief Visuospatial Memory Test - Revised (BVMT-R) Score Up to 7 years Part 2. BVMT-R is used to assess learning/memory. The stimulus page is presented for 10 seconds, and the participant is then asked to reproduce the designs as accurately as possible and in the same location on the page. Three learning trials are administered, followed by a delay trial approximately 20 to 40 minutes later. Immediately following the delay trial a recognition trial is administered to see whether the participant recognizes the figures that were on the display.
Change from Baseline in Weight Up to 7 years Part 2
Change from Baseline in Height Up to 7 years Part 2
Tanner Stage Up to 7 years Part 2. Information regarding Tanner staging will be collected at baseline for all male participants and for female participants who are premenarche and will be stopped once the participant's bone age reaches ≥16 years or once the participant is postmenarche.
Trial Locations
- Locations (62)
MHATNP 'Sv.Naum', EAD
🇧🇬Sofia, Bulgaria
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Hopital Roger Salengro - CHU Lille
🇫🇷Lille Cedex, Nord, France
Szpital Kliniczny im.Heliodora Swiecickiego Uniwersytetu Medycznego im.K. Marcinkowskiego w Poznaniu
🇵🇱Poznan, Poland
Universitair Kinderziekenhuis Koningin Fabiola
🇧🇪Brussels, Belgium
Hadassah University Hospital - Ein Kerem
🇮🇱Jerusalem, Israel
SPZOZ Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa
🇵🇱Bialystok, Poland
Instytut Centrum Zdrowia Matki Polki
🇵🇱Lodz, Poland
Schneider Children's Medical Center
🇮🇱Petach-Tikva, Israel
Azienda Socio Sanitaria Territoriale della Valle Olona (presidio di Gallarate)
🇮🇹Gallarate, Varese, Italy
Heim Pal Orszagos Gyermekgyogyaszati Intezet
🇭🇺Budapest, Hungary
Hospital Sant Joan de Deu
🇪🇸Esplugues de Llobregat, Barcelona, Spain
University Clinical Center Kragujevac
🇷🇸Kragujevac, Serbia
Hospital Universitario Reina Sofia
🇪🇸Cordoba, Córdoba, Spain
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
CHU Clermont Ferrand - Hôpital d'Estaing
🇫🇷Clermont Ferrand, Puy De Dome, France
Universitair Ziekenhuis Ghent
🇧🇪Gent, Belgium
Fakultni nemocnice u sv. Anny v Brne
🇨🇿Brno, Czechia
University of Calgary - Alberta Children's Hospital
🇨🇦Calgary, Alberta, Canada
CHU Dijon -BOCAGE CENTRAL
🇫🇷Dijon, Côte-d'Or, France
Fakultni nemocnice Ostrava
🇨🇿Ostrava, Czechia
Århus Universitetshospital
🇩🇰Aarhus N, Denmark
Odense Universitetshospital
🇩🇰Odense, Denmark
Rigshospitalet
🇩🇰Copenhagen, Denmark
Hopital Gui de Chauliac
🇫🇷Montpellier, Herault, France
Hôpital de la Timone
🇫🇷Marseille, Bouches-du-Rhône, France
CHU Rennes - Hopital Pontchaillou
🇫🇷Rennes cedex 09, Ille Et Vilaine, France
Katholisches Klinikum Bochum gGmbH
🇩🇪Bochum, Nordrhein Westfalen, Germany
Hopital Neurologique Pierre Wertheimer
🇫🇷Bron Cedex, Rhone, France
Universitaetsklinikum Augsburg
🇩🇪Augsburg, Bayern, Germany
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Hôpital Bicêtre
🇫🇷Le Kremlin Bicêtre, Val De Marne, France
CHU Amiens - Hopital Sud
🇫🇷Amiens, Somme, France
Klinikum der Universitaet Muenchen
🇩🇪Muenchen, Bayern, Germany
Ospedale San Raffaele
🇮🇹Milano, Italy
Azienda Ospedale-Università di Padova
🇮🇹Padova, Italy
Ospedale Pediatrico Bambino Gesù
🇮🇹Roma, Italy
Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza
🇮🇹Roma, Italy
Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari
🇮🇹Bari, Italy
IRCCS Ospedale Policlinico San Martino
🇮🇹Genova, Italy
Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
🇮🇹Palermo, Italy
Azienda Ospedaliera Universitaria 'Federico II'
🇮🇹Napoli, Italy
Ibn Sina Hospital
🇰🇼Shuwaikh, Kuwait
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Instytut 'Pomnik - Centrum Zdrowia Dziecka'
🇵🇱Warszawa, Poland
Karolinska
🇸🇪Stockholm, Sweden
Hacettepe University Medical Faculty
🇹🇷Ankara, Turkey
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Sahlgrenska Sjukhuset
🇸🇪Göteborg, Sweden
Evelina London Children's Hospital
🇬🇧London, Greater London, United Kingdom
Akdeniz University Faculty of Medicine
🇹🇷Antalya, Turkey
The National Hospital for Neurology & Neurosurgery
🇬🇧London, Greater London, United Kingdom
Great Ormond Street Hospital for Children
🇬🇧London, Greater London, United Kingdom
Birmingham Children's Hospital
🇬🇧Birmingham, West Midlands, United Kingdom
The Rector and Visitors of the University of Virginia
🇺🇸Charlottesville, Virginia, United States
Nemocnice Jihlava p.o.
🇨🇿Jihlava, Czechia
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Czechia
CHU Strasbourg - Hôpital Hautepierre
🇫🇷Strasbourg, Bas Rhin, France
Hôpital de Brabois Enfants
🇫🇷Vandoeuvre les Nancy Cedex, Meurthe Et Moselle, France
Clinic of Neurology and Psychiatry for Children and Youth
🇷🇸Belgrade, Serbia
Mother and Child Health Care Institute of Serbia ,,Dr Vukan Cupic''
🇷🇸Belgrade, Serbia
Hospital Universitario de Torrejon
🇪🇸Torrejón de Ardoz, Madrid, Spain