Phase 3 Efficacy and Safety Study of BG00012 in Pediatric Participants With Relapsing-Remitting Multiple Sclerosis (RRMS) (CONNECT)

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

The main objectives of Part 1 are as follows: To evaluate the safety, tolerability, and efficacy of BG00012 in pediatric participants 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 participants 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 participants who completed Week 96 in Part 1 of Study 109MS306.

Study Overview

• Status: Completed
• Conditions: Relapsing-Remitting Multiple Sclerosis
• Intervention / Treatment: Drug: dimethyl fumarate; Drug: Interferon β-1a

• Study Type: Interventional
• Enrollment (Actual): 156
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1020
    • Universitair Kinderziekenhuis Koningin Fabiola
  • Ghent, Belgium, 9000
    • Universitair Ziekenhuis Ghent
• Bulgaria
  • Sofia, Bulgaria, 1113
    • MHATNP 'Sv.Naum', EAD
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • University of Calgary - Alberta Children's Hospital
• Czechia
  • Brno, Czechia, 656 91
    • Fakultni nemocnice u sv. Anny v Brne
  • Hradec Králové, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove
  • Jihlava, Czechia, 58633
    • Nemocnice Jihlava p.o.
  • Ostrava, Czechia, 708 52
    • Fakultni nemocnice Ostrava
• Denmark
  • Aarhus N, Denmark, 8200
    • Århus Universitetshospital
  • Copenhagen, Denmark, 2100
    • Rigshospitalet
  • Odense, Denmark, 5000
    • Odense Universitetshospital
• France
  • Bas Rhin
    • Strasbourg, Bas Rhin, France, 67098
      • CHU Strasbourg - Hopital Hautepierre
  • Bouches-du-Rhône
    • Marseille, Bouches-du-Rhône, France, 13385
      • Hopital de la Timone
  • Côte-d'Or
    • Dijon, Côte-d'Or, France, 21079
      • CHU Dijon -BOCAGE CENTRAL
  • Herault
    • Montpellier, Herault, France, 34295
      • Hopital Gui de Chauliac
  • Ille Et Vilaine
    • Rennes, Ille Et Vilaine, France, 35033
      • CHU Rennes - Hôpital Pontchaillou
  • Meurthe Et Moselle
    • Vandœuvre-lès-Nancy, Meurthe Et Moselle, France, 54500
      • Hôpital de Brabois Enfants
  • Nord
    • Lille, Nord, France, 59037
      • Hopital Roger Salengro - CHU Lille
  • Puy De Dome
    • Clermont-Ferrand, Puy De Dome, France, 63003
      • CHU Clermont Ferrand - Hôpital d'Estaing
  • Rhone
    • Bron, Rhone, France, 69677
      • Hopital Neurologique Pierre Wertheimer
  • Somme
    • Amiens, Somme, France, 80054
      • CHU Amiens - Hopital Sud
  • Val De Marne
    • Le Kremlin-Bicêtre, Val De Marne, France, 94275
      • Hôpital Bicêtre
• Germany
  • Bavaria
    • Augsburg, Bavaria, Germany, 86156
      • Universitaetsklinikum Augsburg
    • Munich, Bavaria, Germany, 80337
      • Klinikum der Universitaet Muenchen
  • North Rhine-Westphalia
    • Bochum, North Rhine-Westphalia, Germany, 44791
      • Katholisches Klinikum Bochum gGmbH
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem
  • Budapest, Hungary, 1089
    • Heim Pal Orszagos Gyermekgyogyaszati Intezet
• Israel
  • Jerusalem, Israel, 91120
    • Hadassah University Hospital - Ein Kerem
  • Petah Tikva, Israel, 4920235
    • Schneider Children's Medical Center
  • Ramat Gan, Israel, 5265601
    • Chaim Sheba Medical Center
• Italy
  • Bari, Italy, 70124
    • Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari
  • Genova, Italy, 16132
    • IRCCS Ospedale Policlinico San Martino
  • Milan, Italy, 20132
    • Ospedale San Raffaele
  • Naples, Italy, 80131
    • Azienda Ospedaliera Universitaria 'Federico II'
  • Padova, Italy, 35128
    • Azienda Ospedale-Università di Padova
  • Palermo, Italy, 90127
    • Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
  • Roma, Italy, 00189
    • Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza
  • Roma, Italy, 00165
    • Ospedale Pediatrico Bambino Gesù
  • Varese
    • Gallarate, Varese, Italy, 21013
      • Azienda Socio Sanitaria Territoriale della Valle Olona (presidio di Gallarate)
• Kuwait
  • Ash Shuwaykh, Kuwait, 12345
    • Ibn Sina Hospital
• Poland
  • Bialystok, Poland, 15-274
    • SPZOZ Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa
  • Gdansk, Poland, 80-211
    • Uniwersyteckie Centrum Kliniczne
  • Lodz, Poland, 93-338
    • Instytut Centrum Zdrowia Matki Polki
  • Poznan, Poland, 60-355
    • Szpital Kliniczny im.Heliodora Swiecickiego Uniwersytetu Medycznego im.K. Marcinkowskiego w Poznaniu
  • Warsaw, Poland, 04-730
    • Instytut 'Pomnik - Centrum Zdrowia Dziecka'
• Serbia
  • Belgrade, Serbia, 11000
    • Clinic of Neurology and Psychiatry for Children and Youth
  • Belgrade, Serbia, 11000
    • Mother and Child Health Care Institute of Serbia ,,Dr Vukan Cupic''
  • Kragujevac, Serbia, 34000
    • University Clinical Center Kragujevac
• Spain
  • Seville, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Barcelona
    • Esplugues de Llobregat, Barcelona, Spain, 8950
      • Hospital Sant Joan de Déu
  • Córdoba
    • Córdoba, Córdoba, Spain, 14011
      • Hospital Universitario Reina Sofia
  • Madrid
    • Torrejón de Ardoz, Madrid, Spain, 28850
      • Hospital Universitario de Torrejon
• Sweden
  • Gothenburg, Sweden, 41345
    • Sahlgrenska Sjukhuset
  • Stockholm, Sweden, SE-113 61
    • Karolinska
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06100
    • Hacettepe University Medical Faculty
  • Antalya, Turkey (Türkiye), 07070
    • Akdeniz University Faculty of Medicine
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, WC1N 3BG
      • The National Hospital for Neurology & Neurosurgery
    • London, Greater London, United Kingdom, WC1N 3JH
      • Great Ormond Street Hospital for Children
    • London, Greater London, United Kingdom, SE1 7EH
      • Evelina London Children's Hospital
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B4 6NH
      • Birmingham Children's Hospital
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 2115
      • Boston Children's Hospital
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • The Rector and Visitors of the University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Males and females aged from 10 to less than 18 years old at the time of informed consent or assent.
• Must have a body weight of ≥30 kg.
• Must have a diagnosis of RRMS (consensus definition for pediatric RRMS [Krupp 2013]).
• 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.
• Participants 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. Participants with these conditions may also have superimposed relapses but are distinguished from relapsing-remitting participants 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. Participants 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 participant 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 participant unsuitable for enrollment.

NOTE: Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BG00012; Participants will receive the recommended dose of 240 mg orally, twice a day	Drug: dimethyl fumarate; administered orally; Other Names: BG00012; Tecfidera
Active Comparator: IFN β-1a (Avonex); Participants will receive the recommended dose of 30 μg (weekly)	Drug: Interferon β-1a; administered by intramuscular injection; Other Names: Avonex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Proportion of Participants Free of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans	Participants who were free of new or newly enlarging T2 hyperintense lesions were assessed on Brain MRI scans.	At Week 96
Part 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	An adverse event (AE) was any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE was any untoward medical occurrence that at any dose resulted in death, in the view of the Investigator, placed the participant at immediate risk of death, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a birth defect. TEAEs were defined as AEs occurring or worsening after beginning study treatment (after the first dose).	From Week 96 up to last follow-up visit (up to Week 340)
Part 2: Number of Participants Who Discontinued Study Treatment Due to an AE	An AE was any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.	From Week 96 up to last follow-up visit (up to Week 340)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of New or Newly Enlarged T2 Hyperintense Lesions on Brain MRI Scans	The number of new or newly enlarging T2 hyperintense lesions that developed in each participant was assessed on Brain MRI scans.	At Weeks 24 and Week 96
Part 1: Proportion of Participants Free of New or Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans	Participants who were free of new or newly enlarging T2 hyperintense lesions were assessed on Brain MRI scans.	At Weeks 24 and 48
Part 1: Proportion of Participants Free of New MRI Activity as Measured by Brain MRI Scans	Participants free of Gd-enhancing MRI lesions and new or newly enlarging T2 MRI lesions were assessed on Brain MRI Scans.	At Weeks 24, 48, and 96
Part 1: Time to First Relapse	Relapses are defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the examining neurologist. The time to first relapse was defined as the time from the first dose in Part 1 up to the first relapse. Time to First Relapse was estimated by Kaplan-Meier method.	Up to Week 96
Part 1: Proportion of Relapse-Free Participants	Relapses are defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the examining neurologist. The proportion of relapse-free participants was estimated using the Kaplan-Meier method.	Up to Week 96
Part 1: Annualized Relapse Rate (ARR)	ARR is calculated as the total number of relapses that occurred during the study divided by the total number of participant-years. ARR was analyzed using negative binomial regression model.	At Weeks 48 and 96
Part 1: Number of Participants With TEAEs and TESAEs	An AE was any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE was any untoward medical occurrence that at any dose resulted in death, in the view of the Investigator, placed the participant at immediate risk of death, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a birth defect. TEAEs were defined as AEs occurring or worsening after beginning study treatment (after the first dose).	From Day 1 up to Week 96
Part 1: Change From Baseline in Vital Signs (Temperature)	Negative change from baseline indicated reduction in temperature.	Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84 and 96
Part 1: Change From Baseline in Vital Signs (Pulse Rate)	Negative change from baseline indicated reduction in pulse rate.	Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84 and 96
Part 1: Change From Baseline in Vital Signs (Blood Pressure)	Negative change from baseline indicated reduction in blood pressure.	Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84 and 96
Part 1: Change From Baseline in Vital Signs (Respiratory Rate)	Negative change from baseline indicated reduction in respiratory rate.	Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84 and 96
Part 1: Number of Participants With Shifts From Baseline in Electrocardiograms (ECG) Abnormalities	Clinical significance of abnormalities in ECG was determined based on the investigator's discretion. Shift to abnormal indicated values that were normal or unknown at baseline and shifted to abnormal values post-baseline.	Up to Week 96
Part 1: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters)	Hematology parameters included leukocytes, erythrocytes, hemoglobin, hematocrit, platelets, eosinophils, lymphocytes, monocytes and neutrophils. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available. Here, shift to low indicated values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicated values that were normal, low or unknown at baseline and shifted to high postbaseline values. The categories with at least one participant with shift from baseline in these parameters are reported.	Baseline up to Week 96
Part 1: Change From Baseline in Coagulation Parameters [Activated Partial Thromboplastin Time (aPTT)]	A negative change from baseline indicated a reduction in aPTT.	Baseline, Weeks 24, 48 and 96
Part 1: Change From Baseline in Coagulation Parameters [Prothrombin Time (PT)]	A negative change from baseline indicated a reduction in PT.	Baseline, Weeks 24, 48 and 96
Part 1: Change From Baseline in Coagulation Parameters [International Normalized Ratio (INR)]	A negative change from baseline indicated a reduction in clotting time.	Baseline, Weeks 24, 48 and 96
Part 1: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters)	Parameters included sodium, potassium, chloride, bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, urea nitrogen, creatinine, bicarbonate, calcium, magnesium, phosphate, urate and glucose. These parameters were flagged as low, normal or high relative to parameter's normal range or as unknown if no result was available, by Investigator. Here, shift to low indicated values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicated values that were normal, low or unknown at baseline and shifted to high values postbaseline. Categories with at least one participant with shift from baseline in these parameters are reported.	Baseline up to Week 96
Part 1: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Urinalysis Parameters)	Urinalysis included assessments of glucose, ketones, occult blood, protein, specific gravity. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicated values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicated values that were normal, low or unknown at baseline and shifted to high postbaseline. The categories with at least one participant with shift from baseline in these parameters are reported.	Baseline up to Week 96
Part 1: Fatigue Score Measured by the Pediatric Quality of Life Inventory (PedsQL) Multidimensional Fatigue Scale	The PedsQL multidimensional fatigue questionnaire was answered by the participant (self-assessment) and parent. The fatigue scale contains 18 questions in 3 fatigue dimensions: general fatigue, sleep/rest fatigue and cognitive fatigue. Each item was scored on 5-point Likert scale (0=never to 4=almost always). Each individual score was then reversed (subtracted from 4) and linearly transformed as follows: 0=100, 1=75, 2=50, 3=25, 4=0. For each dimension, total score was calculated as the sum of all the items/number of items answered. A higher total score indicated fewer problems.	Up to Week 96
Part 1: Quality of Life (QOL) as Measured by the PedsQL	The PedsQL QOL questionnaire was answered by the participant (self-assessment) and parent. The QoL scale contains 23 questions in 4 dimensions: Physical Functioning, Emotional Fatigue, Social Fatigue and School Fatigue. Each item was scored on 5-point Likert scale (0=never to 4=almost always). Each individual score was then reversed (subtracted from 4) and linearly transformed as follows: 0=100, 1=75, 2=50, 3=25, 4=0. For each dimension, total score was calculated as the sum of all the items/number of items answered. A higher total score indicated better quality of life.	Up to Week 96
Part 1: Change From Baseline in the Expanded Disability Status Scale (EDSS) Score	The EDSS measures the disability status of participants 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 with higher scores indicating more disability. A negative change from baseline indicated an improvement in the disability.	Baseline, Week 96
Part 2: Annualized Relapse Rate (ARR)	ARR is calculated as the total number of relapses that occurred during the study divided by the total number of participant-years. ARR was analyzed using negative binomial regression model.	From Baseline (Week 96) up to Week 336
Part 2: Change From Baseline in the Expanded Disability Status Scale (EDSS) Score	The EDSS measures the disability status of participants 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. A negative change from baseline indicated an improvement in the disability.	Baseline (Week 96), Week 336
Part 2: Change From Baseline in Brief Visuospatial Memory Test - Revised (BVMT-R) Score	BVMT-R is used to assess learning/memory. In this test, six abstract designs are presented for 10 sec. The display is removed from view, and participants render the stimuli via pencil on paper, manual responses. Each design receives from 0 to 2 points, representing accuracy and location. There are three Learning Trials, and the score is reported as the total number of points earned over the trials. Thus, scores range from 0 to 12 per trial; total score range is 0 to 36 for all three trials. Scores were converted to standardized scores using normative data, ranging from 2-86. The lower the score, the more severe the cognitive impairment while higher scores reflect better visuospatial memory.	Baseline (Week 96), Weeks 144,192, 240, 288 and 336
Part 2: Change From Baseline in Symbol Digit Modalities Test (SDMT) Score	SDMT is used to assess processing speed. It consists of 9 abstract symbols. Each symbol is paired with a single digit. The participant is provided with a key, showing each symbol digit pair. In addition, the participants are shown several rows of the 9 symbols, which are arranged pseudo-randomly, without the digit. Participants are asked to voice the digit associated with each symbol as rapidly as possible for 90 seconds. The SDMT score ranges from 0 to 110, where higher scores indicate improvement in cognitive functioning and lower scores indicate worsening.	Baseline (Week 96), Weeks 144,192, 240, 288 and 336
Part 2: Number of Participants With or Without School Progression	Participants or caregivers were posed the following question: "During the past year, did [you/the participant] progress from one [class/grade-level] to the next in school?" Responses were recorded as Yes (participant advanced to the next grade) or No (participant did not advance).	At Weeks 144, 192, 240, 288 and 336
Part 2: Change From Baseline in Vital Signs (Temperature)	Negative change from baseline indicated reduction in temperature.	Baseline (Week 96), Weeks 120,144, 168, 192, 216, 240, 264, 288, 312, 336, and 340
Part 2: Change From Baseline in Vital Signs (Pulse Rate)	Negative change from baseline indicated reduction in pulse rate.	Baseline (Week 96), Weeks 120,144, 168, 192, 216, 240, 264, 288, 312, 336, and 340
Part 2: Change From Baseline in Vital Signs (Blood Pressure)	Negative change from baseline indicated reduction in blood pressure.	Baseline (Week 96), Weeks 120,144, 168, 192, 216, 240, 264, 288, 312, 336, and 340
Part 2: Change From Baseline in Vital Signs (Respiratory Rate)	Negative change from baseline indicated reduction in respiratory rate.	Baseline (Week 96), Weeks 120,144, 168, 192, 216, 240, 264, 288, 312, 336, and 340
Part 2: Number of Participants With Shifts From Baseline in ECG Abnormalities	Clinical significance of abnormalities in ECG was determined based on the investigator's discretion. Shift to abnormal indicated values that were normal or unknown at baseline and shifted to abnormal values post-baseline.	From Baseline (Week 96) to Week 336
Part 2: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters)	Hematology parameters included leukocytes, erythrocytes, hemoglobin, hematocrit, platelets, eosinophils, lymphocytes, monocytes and neutrophils. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available. Here, shift to low indicated values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicated values that were normal, low or unknown at baseline and shifted to high postbaseline values. The categories with at least one participant with shift from baseline in these parameters are reported.	Baseline (Week 96) up to Week 340
Part 2: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters)	Parameters included potassium, bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, urea nitrogen, creatinine, bicarbonate, calcium, magnesium, phosphate, urate and glucose. These parameters were flagged as low, normal or high relative to parameter's normal range or as unknown if no result was available, by Investigator. Here, shift to low indicated values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicated values that were normal, low or unknown at baseline and shifted to high values postbaseline. Categories with at least one participant with shift from baseline in these parameters are reported.	Baseline (Week 96) up to Week 340
Part 2: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Urinalysis Parameters)	Urinalysis included assessments of erythrocytes, leukocytes and specific gravity. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicated values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicated values that were normal, low or unknown at baseline and shifted to high postbaseline. The categories with at least one participant with shift from baseline in these parameters are reported.	Baseline up to Week 340
Part 2: Change From Baseline in Height		Baseline (Week 96), Weeks 120,144, 168, 192, 216, 240, 264, 288, 312, 336, and 340
Part 2: Change From Baseline in Weight		Baseline (Week 96), Weeks 120,144, 168, 192, 216, 240, 264, 288, 312, 336, and 340
Part 2: Change From Baseline in Bone Age	Bone age was tested until the participant reached a bone age of 16 years.	Baseline (Week 96), Weeks 144, 192 and 240
Part 2: Number of Male Participants by Tanner Stage Assessment	Tanner pubertal staging in males was assessed for testes and scrotum development and pubic hair growth, progressing from stage 1 (prepubertal) to stage 5 (adult). Assessments ended when bone age reached ≥16 years. Testes and scrotum stages were: 1-prepubertal; 2-enlargement of testes, scrotum reddens, texture change; 3-Enlargement of penis, further growth of testes; 4-Increased size of penis with growth in breadth and development of glans; testes and scrotum larger, scrotum skin darker; 5-adult genitalia. Pubic hair stages were: 1-prepubertal; 2-Sparse growth of long, slightly pigmented hair, straight or curled; 3-Darker, coarser and more curled hair, spreading sparsely over junction of pubes; 4-Hair adult in type, but covering smaller area than in adult; no spread to medial surface of thighs; 5-Adult in type and quantity, with horizontal distribution.	At Weeks 96, 144, 192, 240, 288 and 336
Part 2: Number of Female Participants by Tanner Stage Assessment	Tanner pubertal staging in females was assessed for breast development and pubic hair growth, progressing from stage 1 (prepubertal) to stage 5 (adult). Assessments ended when bone age reached ≥16 years or the participant was post-menarche. Breast development stages: 1-prepubertal; 2-breast bud stage with elevation of breast and papilla; enlargement of areola, 3-further enlargement of breast and areola; no separation of their contour; 4-areola and papilla form secondary mound above level of breast; 5-mature stage: projection of papilla only, related to recession of areola. Pubic hair stages: 1-prepubertal (can see velus hair similar to abdominal wall); 2-sparse growth of long, slightly pigmented hair, straight or curled, mainly on labia; 3-Darker, coarser and more curled hair, spreading sparsely over junction of pubes; 4-hair adult in type, but covering smaller area than in adult; no spread to medial surface of thighs; 5-adult in type and quantity, with horizontal distribution.	At Weeks 96, 144, 192, 240, 288 and 336

Collaborators and Investigators

• Sponsor: Biogen
• Investigators: Study Director: Medical Director, Biogen

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2014
• Primary Completion (Actual): July 8, 2025
• Study Completion (Actual): July 8, 2025

Study Registration Dates

• First Submitted: November 3, 2014
• First Submitted That Met QC Criteria: November 4, 2014
• First Posted (Estimated): November 5, 2014

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 16, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Pediatrics
• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Biological Factors; Acids, Acyclic; Carboxylic Acids; Intercellular Signaling Peptides and Proteins; Cytokines; Interferon Type I; Interferons; Fumarates; Dicarboxylic Acids; Interferon-beta; Interferon beta-1a; Dimethyl Fumarate
• Other Study ID Numbers: 109MS306; 2013-002318-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/.

Drug and device information, study documents

• product manufactured in and exported from the U.S.: No