A safety and efficacy study of BG00012 in slowing the progression of disability in patients with Secondary Progressive Multiple Sclerosis.

• Register: EUCTR
• Last refreshed on: 14 December 2015
• Main ID: EUCTR2014-003021-18-DK
• Date of registration: 09/04/2015
• Prospective Registration: Yes
• Primary sponsor: Biogen Idec Research Limited
• Public title: A safety and efficacy study of BG00012 in slowing the progression of disability in patients with Secondary Progressive Multiple Sclerosis.
• Scientific title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of BG00012 in Delaying Disability Progression in Subjects With Secondary Progressive Multiple Sclerosis
• Date of first enrolment: 25/06/2015
• Target sample size: 1170
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-003021-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Argentina, Australia, Austria, Belgium, Bulgaria, Canada, Czech Republic, Denmark, Finland, France, Germany, Hungary, Italy, Netherlands, Norway, Poland, Russian Federation, Serbia, Slovakia, Spain, Sweden, Switzerland, United Kingdom, United States

Contacts

• Name: N/a
• Affiliation: Biogen Idec Research Limited

• Name: N/a
• Affiliation: Biogen Idec Research Limited

Key inclusion & exclusion criteria

Inclusion criteria:
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local subject privacy regulations.
- Age 18 to 58 years, inclusive, at the time of informed consent.
- Onset of SPMS at least 1 to 2 years prior to randomization. SPMS is defined as relapsing remitting disease followed by progression of disability independent of or not explained by relapses.
- Have EDSS score of 3.0 to 6.5, inclusive.
- Have an MS Severity Score of 4 or higher.
- Have documented confirmed evidence of disease progression independent of clinical relapses over the 1 year prior to randomization as defined in the Study Reference Guide.
- Subjects must be able to successfully complete the assessments associated with each component of the primary endpoint (EDSS, T25FW, 9HPT) at Screening, where successful completion of the T25FW and 9HPT is defined as follows:
•At Screening, T25FW completed in =30 seconds
•At Screening, 9HPT completed with each hand in =300 seconds.
- All women of childbearing potential (including female subjects who are post menopausal for less than 1 year) and all men must practice effective contraception throughout the study and be willing and able to continue contraception after their last dose of study treatment (women for 30 days; men for 90 days).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1170
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Have a diagnosis of RRMS or primary progressive MS as defined by the revised McDonald criteria
- Had a recent clinical relapse (within 3 months) prior to randomization
- Subjects for whom MRI is contraindicated (i.e., have pacemakers or other contraindicated implanted metal devices, are allergic to Gd, or have claustrophobia that cannot be medically managed) or for whom the MRI cannot be performed
- Uncontrolled intercurrent illness including, but not limited to- ongoing or active infection; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia; serious or acute liver, kidney, or bone marrow dysfunction; uncontrolled diabetes; serious or acute psychiatric illness that would limit compliance with study requirements
- History of malignancy (subjects with basal cell carcinoma that has been completely excised prior to study entry remain eligible)
- History of human immunodeficiency virus
- History of or positive test result at Screening for hepatitis C virus antibody or hepatitis B virus (defined as positive for hepatitis B surface antigen [HBsAg] or hepatitis B core antibody [HBcAb]). Subjects with immunity to hepatitis B from either active vaccination (defined as negative HBsAg, positive hepatitis B surface antibody [HBsAb] and negative HBcAb) or from previous natural infection (defined as negative HBsAg, positive HBsAb immunoglobulin G, and positive HBcAb) are eligible to participate in the study
- History of severe allergic or anaphylactic reactions or known drug hypersensitivity to fumaric acid or fumaric acid esters
- Any of the following abnormal blood tests at Screening that are confirmed on repeat testing 2 weeks later:
• ALT/serum glutamate-pyruvate transaminase (SGPT), or AST/serum glutamic-oxaloacetic transaminase (SGOT), or gamma-glutamyl-transferase (GGT) =2 times the ULN
• WBC <3500/mm3
• eosinophils >0.7 x 10³/µL or >0.7 GI/L
• absolute lymphocyte count ?LLN.
- Any of the following abnormal urine tests at Screening confirmed by a second urinalysis 2 weeks later:
• proteinuria (1+ or greater)
• hematuria, without known etiology
• glycosuria, without known etiology
- Any previous treatment with BG00012 or any fumaric acid ester containing product
- Prior treatment with any of the following:
• cladribine
• alemtuzumab
• total lymphoid irradiation
• any therapeutic monoclonal antibody, with the exception of natalizumab (Tysabri®), daclizumab, and rituximab
- Treatment with any of the following medications or procedures within the 6 months prior to randomization:
• mitoxantrone
• cyclophosphamide
• cyclosporine
• azathioprine
• teriflunomide
• methotrexate
• natalizumab
• daclizumab
• rituximab
• fingolimod
• mycophenolate mofetil
• T-cell or T-cell receptor vaccination
• laquinimod
• cytapheresis
- Treatment with any of the following within the 3 months prior to randomization:
• intravenous (IV) steroids or oral corticosteroids
• IV IG
• plasmapheresis
- Treatment with any of the following within the 4 weeks prior to randomization:
• subcutaneous or oral glatiramer acetate
• interferon-ß
- Treatment with fampridine within 30 days prior to randomization, unless a stable dose has been maintained for at least 30 days prior to randomization and will be continued for the course of this study.
- Treatment with another investigational drug or approved therapy for investigational use within the 6 months prior to randomization
- Female subjects who are p

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Secondary Progressive Multiple Sclerosis
MedDRA version: 17.1 Level: PT Classification code 10063400 Term: Secondary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: BG00012
Product Code: BG00012
Pharmaceutical Form: Gastro-resistant capsule, hard
INN or Proposed INN: Dimethyl Fumarate
CAS Number: 624-49-7
Current Sponsor code: BG00012
Other descriptive name: Dimethyl Fumarate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 120-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To assess the effect of BG00012 compared with placebo on patient-reported outcomes, brain atrophy, and cognitive function

Timepoint(s) of evaluation of this end point: Every 12 weeks

Main Objective: The primary objective of the study is to investigate whether treatment with BG00012 compared with placebo slows the accumulation of disability not related to relapses in subjects with SPMS.

Primary end point(s): The primary endpoint is time to disability progression independent of relapse, where progressors are defined as subjects who meet at least 1 of the following criteria confirmed at a second visit =6 months later and at Week 108 (or at the last available study visit for subjects who withdraw from the study early):
- EDSS: increase from Baseline of =1 point if Baseline EDSS =5.5, or =0.5 point if Baseline EDSS =6.0
- T25FW: =20% increase from Baseline in the time taken for the 25-foot walk
- 9HPT: =20% increase from Baseline in the time taken for the 9HPT (increase must be confirmed in the same hand)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Every 12 weeks, except for the change in the whole brain volume, which will be evaludated at Week 108

Secondary end point(s): - Change from Baseline to 2 years on the 12 Item Multiple Sclerosis Walking Scale (MSWS 12)
- Change from Baseline to Week 108 in ABILHAND Questionnaire score
- Percentage change from Baseline to Week 108 in whole brain volume
- Change from Baseline to Week 108 in cognitive function as measured by the SDMT

Secondary ID(s)

2014-003021-18-SE

109MS308

Source(s) of Monetary Support

Biogen Idec Research Limited