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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Biogen Idec Research Limited

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

24 Jul 2014 → 8 Jul 2025

Decision date (initial)

2024-10-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-505632-35-00

EudraCT number

2013-002318-11

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

The main objectives of Part 1 are as follows:
• To evaluate the safety, tolerability, and efficacy on the disease course of BG00012 (dimethyl fumarate) in subjects with RRMS, as compared with a disease modifying treatment.
• 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.

Secondary objectives 1

1. The secondary objective of Part 2: To describe the long-term MS outcomes of BG00012 in subjects who completed Week 96 in Part 1 of Study 109MS306.

Conditions and MedDRA coding

Relapsing-Remitting Multiple Sclerosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Must have a body weight of ≥30 kg.
2. Must have a diagnosis of RRMS (consensus definition for pediatric RRMS [Krupp 2013]).
3. Must be ambulatory with a baseline EDSS score between 0 and 5.5, inclusive.
4. Must have experienced at least 1 relapse within the last 12 months prior to Day 1 or at least 2 relapses within the last 24 months prior to Day 1, with a prior brain MRI demonstrating lesions consistent with MS, or evidence of Gd enhancing lesions of the brain on an MRI performed within the 6 weeks prior to Day 1.
5. 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.
6. 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.
7. Part 2: Subjects who have completed Week96 in Part 1

Exclusion criteria 16

1. 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.
2. 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.
3. History of premalignant or malignant disease. Subjects with basal cell carcinoma that has been completely excised prior to screening will remain eligible.
4. History of severe allergic or anaphylactic reactions, or known drug hypersensitivity to DMF, fumaric acid esters or interferon β-1a (IFN β1a).
5. 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.
6. 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.
7. History of human immunodeficiency virus.
8. 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.
9. Other unspecified reasons that, in the opinion of the Investigator or Biogen Idec, make the subject unsuitable for enrollment.
10. Key Treatment history - Any previous treatment with Fumaderm (fumaricacid esters) or BG00012
11. Prior treatment with any of the following: total lymphoid irradiation, cladribine, Tcell or Tcell receptor vaccination, any therapeutic monoclonal antibody, with the exception of rituximab or natalizumab.
12. Prior treatment with any of the following medications within the 12 months prior to Day 1: mitoxantrone, cyclophosphamide, rituximab.
13. 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
14. 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]), 4aminopyridine or related products (except subjects on a stable dose of controlled release fampridine for 3 months)
15. Part 2: Any significant changes in medical history occurring after enrollment in Part 1
16. Subjects who could not tolerate BG00012 in Part 1

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The primary endpoint of Part 1 of the study is the proportion of participants free of new/newly enlarging T2 hyperintense lesions on brain MRI scans at Week 96.
2. The primary endpoint of the Part 2 is the incidence of adverse events, serious adverse events and discontinuations of BG00012 due to an adverse event

Secondary endpoints 11

1. Part 1: Number of new/newly enlarging T2 hyperintense lesions on brain MRI scans at Weeks 24 and 96
2. Proportion of participants free of new/newly enlarging T2 hyperintense lesions on brain MRI scans at Weeks 24 and 48
3. Proportion of participants free of new MRI activity (new MRI activity includes: Gd enhancing MRI lesion on brain MRI scans; new T2 MRI lesions on brain MRI scans and newly enlarging LRI lesions on brain MRI scans) at Weeks 24, 48, and 96
4. Time to first relapse up to week 96
5. Proportion of participants who do not experience relapse up to Week 96
6. Annualized relapse rate at Weeks 48 and 96
7. Number of participants that experience Adverse Events (AEs) and serious adverse events (SAEs) Including prospective and followup of flushing, nausea, abdominal pain and diarrhea up to Week 96
8. Fatigue as measured by the Pediatric Quality of Life Inventory (PedsQL) Multidimensional Fatigue Scale scores up to Week 96
9. Change from baseline to Week 96 in the Expanded Disability Status Scale (EDSS) score up to Week 96.
10. 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.
11. Part 2: include annualized relapse rate; EDSS; cognition as measured by BVMT-R, SDMT, and school progression query; vital signs; ECGs; clinical laboratory data; changes from baseline in height, weight, and bone age; and Tanner stage.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Biogen Idec Research Limited

Sponsor organisation

Biogen Idec Research Limited

Address

Innovation House, 70 Norden Road 70 Norden Road

City

Maidenhead

Postcode

SL6 4AY

Country

United Kingdom

Scientific contact point

Organisation

Biogen Idec Research Limited

Contact name

Clinical Trials Information Desk

Public contact point

Organisation

Biogen Idec Research Limited

Contact name

Clinical Trials Information Desk

Third parties 7

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 33 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications