Clinical trial NCT02283853: Phase 3 Efficacy and Safety Study of BG00012 in Pediatric Subjects With Relapsing-remitting Multiple Sclerosis (RRMS)
Official title: Open-Label, Randomized, Multicenter, Multiple-Dose,Active-Controlled, Parallel-Group, Efficacy and Safety Study of BG00012 in Children From 10 to Less Than 18 Years of Age With Relapsing-Remitting Multiple Sclerosis, With Optional Open-Label Extension
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Relapsing-Remitting Multiple Sclerosis
Keywords: Pediatrics
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2014-11-05
Enrollment: 156
Sex: ALL
Minimum age (years): 10
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key Inclusion Criteria:

* 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 Exclusion Criteria:

* 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.
* 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.
* History of severe allergic or anaphylactic reactions, or known drug hypersensitivity to DMF, fumaric acid esters, or interferon beta-1a (IFN Beta-1a).
* 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.
* 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.
* 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.
* Other unspecified reasons that, in the opinion of the Investigator or Biogen Idec, make the subject unsuitable for enrollment.
* 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

Primary outcomes:
measure: Proportion of Participants Free of New/Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans
timeFrame: At week 96
measure: Number of Participants That Experience Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: Up to 7 years
measure: Number of Participants Who Discontinue Study Treatment due to an AE
timeFrame: Up to 7 years
Secondary outcomes:
measure: The Number of New/Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans
timeFrame: At Week 24 and Week 96
measure: Proportion of Participants Free of New/Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans
timeFrame: At Week 24 and Week 48
measure: Proportion of Participants Free of New MRI Activity as measured by Brain MRI Scans
timeFrame: At Weeks 24, 48 and 96
measure: Time to First Relapse
timeFrame: Up to Week 96
measure: Proportion of Participants Who Do Not Experience Relapse
timeFrame: Up to Week 96
measure: Annualized Relapse Rate
timeFrame: At Weeks 48 and 96
measure: Number of Participants That Experience Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Week 96
measure: Fatigue as measured by the Pediatric Quality of Life Inventory (PedsQL) Multidimensional Fatigue Scale Scores
timeFrame: Up to Week 96
measure: Quality of Life as measured by the PedsQL
timeFrame: Up to Week 96
measure: Change from Baseline to Week 96 in the Expanded Disability Status Scale (EDSS) Score
timeFrame: Up to Week 96
measure: Vital Signs, Electrocardiograms (ECGs) and Changes in Clinical Laboratory Data, including Monitoring of Liver Function, Renal Function, Hematologic, and Coagulation Parameters
timeFrame: Up to Week 96
measure: Annualized Relapse Rate
timeFrame: Up to 7 years
measure: Change from Baseline in EDSS Score
timeFrame: Up to 7 years
measure: Change from Baseline in Symbol Digit Modalities Test (SDMT) Score
timeFrame: Up to 7 years
measure: Change from Baseline in Brief Visuospatial Memory Test - Revised (BVMT-R) Score
timeFrame: Up to 7 years
measure: Change from Baseline in School Progression Query
timeFrame: Up to 7 years
measure: Number of Participants with Incidences of Clinically Relevant Vital Signs Abnormalities
timeFrame: Up to 7 years
measure: Number of Participants with Incidences of Clinically Relevant ECG Abnormalities
timeFrame: Up to 7 years
measure: Number of Participants with Incidences of Clinically Relevant Laboratory Assessment Abnormalities
timeFrame: Up to 7 years
measure: Change from Baseline in Height
timeFrame: Up to 7 years
measure: Change from Baseline in Weight
timeFrame: Up to 7 years
measure: Change from Baseline in Bone Age
timeFrame: Up to 7 years
measure: Tanner Stage
timeFrame: Up to 7 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Charlottesville
country: United States
facility: The Rector and Visitors of the University of Virginia
state: Virginia
city: Brussels
country: Belgium
facility: Universitair Kinderziekenhuis Koningin Fabiola
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Ghent
city: Sofia
country: Bulgaria
facility: MHATNP 'Sv.Naum', EAD
city: Calgary
country: Canada
facility: University of Calgary - Alberta Children's Hospital
state: Alberta
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Jihlava
country: Czechia
facility: Nemocnice Jihlava p.o.
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Aarhus N
country: Denmark
facility: Århus Universitetshospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Odense
country: Denmark
facility: Odense Universitetshospital
city: Strasbourg
country: France
facility: CHU Strasbourg - Hôpital Hautepierre
state: Bas Rhin
city: Marseille
country: France
facility: Hôpital de la Timone
state: Bouches-du-Rhône
city: Dijon
country: France
facility: CHU Dijon -BOCAGE CENTRAL
state: Côte-d'Or
city: Montpellier
country: France
facility: Hopital Gui de Chauliac
state: Herault
city: Rennes cedex 09
country: France
facility: CHU Rennes - Hopital Pontchaillou
state: Ille Et Vilaine
city: Vandoeuvre les Nancy Cedex
country: France
facility: Hôpital de Brabois Enfants
state: Meurthe Et Moselle
city: Lille Cedex
country: France
facility: Hopital Roger Salengro - CHU Lille
state: Nord
city: Clermont Ferrand
country: France
facility: CHU Clermont Ferrand - Hôpital d'Estaing
state: Puy De Dome
city: Bron Cedex
country: France
facility: Hopital Neurologique Pierre Wertheimer
state: Rhone
city: Amiens
country: France
facility: CHU Amiens - Hopital Sud
state: Somme
city: Le Kremlin Bicêtre
country: France
facility: Hôpital Bicêtre
state: Val De Marne
city: Augsburg
country: Germany
facility: Universitaetsklinikum Augsburg
state: Bayern
city: Muenchen
country: Germany
facility: Klinikum der Universitaet Muenchen
state: Bayern
city: Bochum
country: Germany
facility: Katholisches Klinikum Bochum gGmbH
state: Nordrhein Westfalen
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Heim Pal Orszagos Gyermekgyogyaszati Intezet
city: Jerusalem
country: Israel
facility: Hadassah University Hospital - Ein Kerem
city: Petach-Tikva
country: Israel
facility: Schneider Children's Medical Center
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Gallarate
country: Italy
facility: Azienda Socio Sanitaria Territoriale della Valle Olona (presidio di Gallarate)
state: Varese
city: Bari
country: Italy
facility: Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico San Martino
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria 'Federico II'
city: Padova
country: Italy
facility: Azienda Ospedale-Università di Padova
city: Palermo
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesù
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza
city: Shuwaikh
country: Kuwait
facility: Ibn Sina Hospital
city: Bialystok
country: Poland
facility: SPZOZ Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Lodz
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki
city: Poznan
country: Poland
facility: Szpital Kliniczny im.Heliodora Swiecickiego Uniwersytetu Medycznego im.K. Marcinkowskiego w Poznaniu
city: Warszawa
country: Poland
facility: Instytut 'Pomnik - Centrum Zdrowia Dziecka'
city: Belgrade
country: Serbia
facility: Clinic of Neurology and Psychiatry for Children and Youth
city: Belgrade
country: Serbia
facility: Mother and Child Health Care Institute of Serbia ,,Dr Vukan Cupic''
city: Kragujevac
country: Serbia
facility: University Clinical Center Kragujevac
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Deu
state: Barcelona
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
state: Córdoba
city: Torrejón de Ardoz
country: Spain
facility: Hospital Universitario de Torrejon
state: Madrid
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Göteborg
country: Sweden
facility: Sahlgrenska Sjukhuset
city: Stockholm
country: Sweden
facility: Karolinska
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: Antalya
country: Turkey
facility: Akdeniz University Faculty of Medicine
city: London
country: United Kingdom
facility: Evelina London Children's Hospital
state: Greater London
city: London
country: United Kingdom
facility: The National Hospital for Neurology & Neurosurgery
state: Greater London
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
state: Greater London
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
state: West Midlands
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Vermersch P, Scaramozza M, Levin S, Alroughani R, Deiva K, Pozzilli C, Lyons J, Mokliatchouk O, Pultz J, N'Dure F, Liu S, Badwan R, Branco F, Hood-Humphrey V, Franchimont N, Hanna J, Maghzi AH. Effect of Dimethyl Fumarate vs Interferon beta-1a in Patients With Pediatric-Onset Multiple Sclerosis: The CONNECT Randomized Clinical Trial. JAMA Netw Open. 2022 Sep 1;5(9):e2230439. doi: 10.1001/jamanetworkopen.2022.30439.