Phase 3 Efficacy and Safety Study of BG00012 in Pediatric Subjects With Relapsing-remitting Multiple Sclerosis (RRMS)

Relapsing-Remitting Multiple Sclerosis Clinical Trial

— CONNECT  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02283853
• Other study ID #: 109MS306
• Secondary ID: 2013-002318-11
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 28, 2014
• Est. completion date: September 8, 2025

Study information

• Verified date: June 2024
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 156
• Est. completion date: September 8, 2025
• Est. primary completion date: September 8, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Relapsing-Remitting Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• dimethyl fumarate
administered orally
• Interferon ß-1a
administered by intramuscular injection

Locations

Country	Name	City	State
Belgium	Research Site	Brussels
Belgium	Research Site	Gent
Bulgaria	Research Site	Sofia
Canada	Research Site	Calgary
Czechia	Research Site	Brno
Czechia	Research Site	Hradec Kralove
Czechia	Research Site	Jihlava
Czechia	Research Site	Ostrava - Poruba
Denmark	Research Site	Århus C
Denmark	Research Site	København
Denmark	Research Site	Odense
France	Research Site	Amiens Cedex 1	Somme
France	Research Site	Bron Cedex	Rhone
France	Research Site	Clermont Ferrand
France	Research Site	Dijon Cedex	Cote dÝOr
France	Research Site	Le Kremlin Bicêtre
France	Research Site	Lille Cedex
France	Research Site	Marseille
France	Research Site	Montpellier
France	Research Site	Rennes cedex 09	Ille Et Vilaine
France	Research Site	Strasbourg	Bas Rhin
France	Research Site	Vandoeuvre les Nancy	Vandoeuvre Les Nancy Cedex
Germany	Research Site	Augsburg	Bayern
Germany	Researh Site	Bochum
Germany	Research Site	Muenchen
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Israel	Research Site	Jerusalem
Israel	Research Site	Petach-Tikva
Israel	Resaerch Site	Ramat-Gan
Italy	Research Site	Bari
Italy	Research Site	Gallarate	Varese
Italy	Research Site	Genova
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Padova
Italy	Research Site	Palermo
Italy	Research Site	Rome
Italy	Research Site	Rome
Kuwait	Research Site	Kuwait	Shuwaikh
Poland	Research Site	Bialystok
Poland	Research Site	Gdansk
Poland	Research Site	Lodz
Poland	Research Site	Poznan
Poland	Research Site	Warsaw
Serbia	Research Site	Belgrade
Serbia	Research Site	Belgrade
Serbia	Resaerch Site	Kragujevac
Spain	Research Site	Barcelona
Spain	Resaeach Site	Cordoba
Spain	Research Site	Madrid
Spain	Resaerch Site	Sevilla
Sweden	Research Site	Göteborg
Sweden	Research Site	Stockholm
Turkey	Research Site	Ankara
Turkey	Research Site	Antalya
United Kingdom	Research Site	Birmingham	West Midlands
United Kingdom	Research Site	London
United Kingdom	Research Site	London	Greater London
United Kingdom	Research Site	London	Greater London
United States	Research Site	Boston	Massachusetts
United States	Research Site	Charlottesville	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Belgium,  Bulgaria,  Canada,  Czechia,  Denmark,  France,  Germany,  Hungary,  Israel,  Italy,  Kuwait,  Poland,  Serbia,  Spain,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Participants Free of New/Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans	Part 1	At week 96
Primary	Number of Participants That Experience Adverse Events (AEs) or Serious Adverse Events (SAEs)	Part 2 will be an optional open-label extension phase in subjects who complete Part 1 and who meet the Part 2 entry criteria.	Up to 7 years
Primary	Number of Participants Who Discontinue Study Treatment due to an AE	Part 2	Up to 7 years
Secondary	The Number of New/Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans	Part 1	At Week 24 and Week 96
Secondary	Proportion of Participants Free of New/Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans	Part 1	At Week 24 and Week 48
Secondary	Proportion of Participants Free of New MRI Activity as measured by Brain MRI Scans	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	At Weeks 24, 48 and 96
Secondary	Time to First Relapse	Part 1	Up to Week 96
Secondary	Proportion of Participants Who Do Not Experience Relapse	Part 1	Up to Week 96
Secondary	Annualized Relapse Rate	Part 1	At Weeks 48 and 96
Secondary	Number of Participants That Experience Adverse Events (AEs) and Serious Adverse Events (SAEs)	Part 1. Including prospective and follow-up of flushing, nausea, abdominal pain and diarrhea	Up to Week 96
Secondary	Fatigue as measured by the Pediatric Quality of Life Inventory (PedsQL) Multidimensional Fatigue Scale Scores	Part 1. Multidimensional Fatigue Scale scores - designed as a generic symptom-speci?c instrument to measure fatigue in patients with acute and chronic health conditions as well as healthy school and community populations.	Up to Week 96
Secondary	Quality of Life as measured by the PedsQL	Part 1	Up to Week 96
Secondary	Change from Baseline to Week 96 in the Expanded Disability Status Scale (EDSS) Score	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.	Up to Week 96
Secondary	Vital Signs, Electrocardiograms (ECGs) and Changes in Clinical Laboratory Data, including Monitoring of Liver Function, Renal Function, Hematologic, and Coagulation Parameters	Part 1	Up to Week 96
Secondary	Annualized Relapse Rate	Part 2	Up to 7 years
Secondary	Change from Baseline in EDSS Score	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.	Up to 7 years
Secondary	Change from Baseline in Symbol Digit Modalities Test (SDMT) Score	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.	Up to 7 years
Secondary	Change from Baseline in Brief Visuospatial Memory Test - Revised (BVMT-R) Score	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.	Up to 7 years
Secondary	Change from Baseline in School Progression Query	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?"	Up to 7 years
Secondary	Number of Participants with Incidences of Clinically Relevant Vital Signs Abnormalities	Part 2	Up to 7 years
Secondary	Number of Participants with Incidences of Clinically Relevant ECG Abnormalities	Part 2	Up to 7 years
Secondary	Number of Participants with Incidences of Clinically Relevant Laboratory Assessment Abnormalities	Part 2	Up to 7 years
Secondary	Change from Baseline in Height	Part 2	Up to 7 years
Secondary	Change from Baseline in Weight	Part 2	Up to 7 years
Secondary	Change from Baseline in Bone Age	Part 2	Up to 7 years
Secondary	Tanner Stage	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.	Up to 7 years