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

• Sponsor: Biogen (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02283853
• Collaborator: (none)
• Enrollment: 156
• Locations: 62
• Arms: 2
• Anticipated Duration (Months): 132.4
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Relapsing-Remitting Multiple Sclerosis	Drug: dimethyl fumarate; Drug: Interferon β-1a	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 156 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Aug 28, 2014
• Anticipated Primary Completion Date: Sep 8, 2025
• Anticipated Study Completion Date: Sep 8, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Proportion of Participants Free of New/Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans [At week 96]

   Part 1

2. 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.

3. Number of Participants Who Discontinue Study Treatment due to an AE [Up to 7 years]

   Part 2

Secondary Outcome Measures

1. The Number of New/Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans [At Week 24 and Week 96]

   Part 1

2. Proportion of Participants Free of New/Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans [At Week 24 and Week 48]

   Part 1

3. 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

4. Time to First Relapse [Up to Week 96]

   Part 1

5. Proportion of Participants Who Do Not Experience Relapse [Up to Week 96]

   Part 1

6. Annualized Relapse Rate [At Weeks 48 and 96]

   Part 1

7. 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

8. 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.

9. Quality of Life as measured by the PedsQL [Up to Week 96]

   Part 1

10. 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.

11. 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

12. Annualized Relapse Rate [Up to 7 years]

    Part 2

13. 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.

14. 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.

15. 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.

16. 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?"

17. Number of Participants with Incidences of Clinically Relevant Vital Signs Abnormalities [Up to 7 years]

    Part 2

18. Number of Participants with Incidences of Clinically Relevant ECG Abnormalities [Up to 7 years]

    Part 2

19. Number of Participants with Incidences of Clinically Relevant Laboratory Assessment Abnormalities [Up to 7 years]

    Part 2

20. Change from Baseline in Height [Up to 7 years]

    Part 2

21. Change from Baseline in Weight [Up to 7 years]

    Part 2

22. Change from Baseline in Bone Age [Up to 7 years]

    Part 2

23. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Boston	Massachusetts	United States	02115
2	Research Site	Charlottesville	Virginia	United States	22903
3	Research Site	Brussels		Belgium	1020
4	Research Site	Gent		Belgium	9000
5	Research Site	Sofia		Bulgaria	1113
6	Research Site	Calgary		Canada	T3B 6A8
7	Research Site	Brno		Czechia	656 91
8	Research Site	Hradec Kralove		Czechia	500 05
9	Research Site	Jihlava		Czechia	58633
10	Research Site	Ostrava - Poruba		Czechia	708 52
11	Research Site	København		Denmark	2100
12	Research Site	Odense		Denmark	5000
13	Research Site	Århus C		Denmark	8000
14	Research Site	Strasbourg	Bas Rhin	France	67098
15	Research Site	Dijon Cedex	Cote dÝOr	France	21033
16	Research Site	Rennes cedex 09	Ille Et Vilaine	France	35033
17	Research Site	Bron Cedex	Rhone	France	69677
18	Research Site	Amiens Cedex 1	Somme	France	80054
19	Research Site	Vandoeuvre les Nancy	Vandoeuvre Les Nancy Cedex	France	54511
20	Research Site	Clermont Ferrand		France	63003
21	Research Site	Le Kremlin Bicêtre		France	94275
22	Research Site	Lille Cedex		France	59037
23	Research Site	Marseille		France	13385
24	Research Site	Montpellier		France	34295
25	Research Site	Augsburg	Bayern	Germany	86156
26	Researh Site	Bochum		Germany	44791
27	Research Site	Muenchen		Germany	80337
28	Research Site	Budapest		Hungary	1083
29	Research Site	Budapest		Hungary	1089
30	Research Site	Jerusalem		Israel	91120
31	Research Site	Petach-Tikva		Israel	4920235
32	Resaerch Site	Ramat-Gan		Israel	52621
33	Research Site	Gallarate	Varese	Italy	21013
34	Research Site	Bari		Italy	70124
35	Research Site	Genova		Italy	16132
36	Research Site	Milano		Italy	20132
37	Research Site	Napoli		Italy	80131
38	Research Site	Padova		Italy	35128
39	Research Site	Palermo		Italy	90127
40	Research Site	Rome		Italy	00165
41	Research Site	Rome		Italy	00189
42	Research Site	Kuwait	Shuwaikh	Kuwait	73767
43	Research Site	Bialystok		Poland	15-274
44	Research Site	Gdansk		Poland	80-952
45	Research Site	Lodz		Poland	93-338
46	Research Site	Poznan		Poland	60-355
47	Research Site	Warsaw		Poland	04-730/20
48	Research Site	Belgrade		Serbia	11000
49	Research Site	Belgrade		Serbia	11070
50	Resaerch Site	Kragujevac		Serbia	34000
51	Research Site	Barcelona		Spain	8036
52	Resaeach Site	Cordoba		Spain	14011
53	Research Site	Madrid		Spain	28850
54	Resaerch Site	Sevilla		Spain	41009
55	Research Site	Göteborg		Sweden	41345
56	Research Site	Stockholm		Sweden	17176
57	Research Site	Ankara		Turkey	06100
58	Research Site	Antalya		Turkey	07070
59	Research Site	London	Greater London	United Kingdom	SE1 7EH
60	Research Site	London	Greater London	United Kingdom	WC1N 3JH
61	Research Site	Birmingham	West Midlands	United Kingdom	B4 6NH
62	Research Site	London		United Kingdom	WC1N 3BG

Sponsors and Collaborators

• Biogen

Investigators

• Study Director: Medical Director, Biogen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Biogen
• ClinicalTrials.gov Identifier: NCT02283853
• Other Study ID Numbers: 109MS306; 2013-002318-11
• First Posted: Nov 5, 2014
• Last Update Posted: Jan 13, 2022
• Last Verified: Jan 1, 2022

• Keywords provided by Biogen: Pediatrics
• Additional relevant MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis; Interferons; Interferon-beta; Interferon beta-1a; Dimethyl Fumarate

Study Results

No Results Posted as of Jan 13, 2022