Relapsing forms of multiple sclerosis MedDRA version: 19.0 Level: PT Classification code 10063400 Term: Secondary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders MedDRA version: 19.0 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: BIIB033
Product Code: BIIB033
Pharmaceutical Form: Solution for infusion
Current Sponsor code: BIIB033
Other descriptive name: Human anti-LINGO-1 monoclonal antibody
Concentration unit:
Sponsors
Biogen Idec Research Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Ability to understand the purpose and risks of the study and provide signed and dated Informed Consent Form (ICF) and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations. 2. Aged 18 to 58 years old, inclusive, at the time of informed consent. 3. Diagnosis of RRMS per the 2005 McDonald's criteria or onset of SPMS per the Lublin and Reingold criteria. 4. For RRMS, subjects must have disease activity as defined by 2 or more distinct occurrences of any of the following 3 events within 12 months of enrollment: Clinical relapse Gd+ lesion on MRI (brain or spinal cord MRI) New T2 lesion on MRI (brain or spinal cord MRI) 5. For SPMS, subjects must have disease activity as defined by 1 or more distinct occurrences of any of the following 2 events within 12 months of enrollment: Clinical relapse Gd+ lesion on MRI (brain or spinal cord MRI) 6. Baseline EDSS score of 2 to 6. 7. All male and female subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for at least 6 months after their last dose of study treatment (BIIB033 plus Avonex or placebo plus Avonex). 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 396 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. History of abnormal laboratory results that in the opinion of the Investigator, are indicative of an significant cardiac, endocrine, hematologic, immunologic, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric, renal, neurologic (other than MS) and/or other major disease that would preclude administration of BIIB033 and/or Avonex. 2. Any of the following abnormal blood tests at screening: hemoglobin = 9.0 g/dL platelets =100 X 109/L lymphocytes =1.0 X 109/L neutrophils =1.5 X 109/L alanine aminotransferase/serum glutamate pyruvate transaminase (ALT/SGPT), aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), or gamma-glutamyl-transferase = 2 times the upper limit of normal (ULN) serum creatinine =ULN 3. Treatment with Botox for limb spasticity within 6 months before Day 1/Baseline. 4. Plans to undergo elective major procedures/surgeries at any time during the study. 5. Simultaneous participation in another study protocol. 6. Treatment with any investigational MS drugs within 3 weeks or 5 t1/2 (whichever is longer) prior to Day 1/Baseline. 7. Treatment with high dose oral or IV steroids =30 days before Day 1/Baseline. 8. History of suicidal ideation or an episode of clinically severe depression (as determined by the Investigator) within 3 months of enrollment. Note: subjects receiving ongoing antidepressant therapy will not be excluded from the study unless the medication has been increased within the 6 months prior to enrollment. 9. RRMS subjects with any history of inadequate response to any approved (in country of residence) interferon ß preparation (e.g., Avonex, Rebif, interferon ß-1b, or any generic interferon ß). (Inadequate response definition: 2 or more distinct occurrences of clinical relapse and/or Gd+ lesion on MRI and/or new or non-enhancing lesion on MRI within any 12-month period while compliant with interferon ß.) 10. History of human immunodeficiency virus or other immunodeficient conditions. 11. History of positive test result for hepatitis C virus Ab or Hepatitis B virus (defined as positive for hepatitis B surface antigen or hepatitis B core Ab). 12. History of drug or alcohol abuse (as defined by the Investigator) within 2 years prior to randomization. 13. History of seizure disorder or unexplained blackouts OR history of a seizure within 6 months prior to Baseline. 14. Female subjects who have a positive pregnancy test, are pregnant, or currently breast feeding. 15. T25FW >30 seconds (any of the 2 tests at Screening). 16. History of malignancy; however subjects with a history or excised or treated basal cell carcinoma or fewer than 3 squamous cell carcinomas are eligible to participate in this study. 17. Renal impairment with a creatinine clearance <80 mL/minute at Screening (creatinine clearance estimated by Cockcroft-Gault equation). 18. In the opinion of the Investigator, a history of clinically significant persistent neutralizing Ab against interferon ß. 19. Known intolerance, contraindication to, or history of noncompliance with Avonex. 20. Treatment with fingolimod or investigational sphingosine 1- phosphate receptor 1 (S1P1) agonists within 3 months prior to Day 1/Baseline. 21. Treatment with natalizumab within 3 months prior to Day 1/Baseline. 22. Initiation of treatment or dose adjustment of commercially available 4-aminopyridine (4-AP) or related products within the last 28 days. Note: subjects
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate the efficacy of BIIB033 in subjects with active relapsing MS when used concurrently with Avonex.;Secondary Objective: Secondary objectives of this study in this study population are to assess the safety, tolerability, and population PK of BIIB033 when used concurrently with Avonex.;Primary end point(s): Primary Efficacy Endpoint: Percentage of subjects experiencing confirmed improvement of neurophysical and/or cognitive function over 72 weeks (approximately 18 months) of treatment as measured by a composite endpoint comprising the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), and (3-Second) Paced Auditory Serial Addition Test (PASAT). Improvement on neuro-physical and/or cognitive function is defined as at least 1 of the following: A =1.0 point decrease in EDSS from a baseline score of =6.0 (decrease sustained for 3 months or greater). A =15% improvement from baseline in T25FW (improvement sustained for 3 months or greater). A =15% improvement from baseline in 9HPT (improvement sustained for 3 months or greater). A =15% improvement from baseline in PASAT (improvement sustained for 3 months or greater).;Timepoint(s) of evaluation of this end point: Quarterly over 72 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints: Percentage of subjects experiencing confirmed worsening of neurophysical and/or cognitive function and/or disability over 72 weeks (approximately 18 months) of treatment as measured by a composite endpoint of the EDSS, T25FW, 9HPT, and PASAT. Progression of disability or worsening of neuro-physical and/or cognitive function is defined as at least 1 of the following: A =1.0 point increase in EDSS from a baseline score of =5.5 or a =0.5 point increase from a baseline score equal to 6.0 (increase sustained for 3 months orgreater). A =15% worsening from baseline in T25FW (worsening sustained for 3 months or greater). A =15% worsening from baseline in 9HPT (worsening sustained for 3 months or greater). A =15% worsening from baseline in PASAT (worsening sustained for 3 months or greater).Safety Endpoints The following safety parameters will be used to address the safety and tolerability portion of the secondary objectives: Adverse events (AEs) Serious adverse events (SAEs) Clinical laboratory test results Physical examination findings Electrocardiogram (ECG) Vital signs results Weight Serum antibodies (Ab) to BIIB033 Disease activity by brain MRI metrics MS signs and symptoms Columbia Suicide Severity Rating Scale (C-SSRS) score Pharmacokinetic Endpoint The PK portion of the secondary objectives will be addressed by the following: BIIB033 population PK assessment;Timepoint(s) of evaluation of this end point: Efficacy Assessments: Quarterly over 72 weeks Safety Assessments and PK/PD Sampling: at specified timepoints during the treatment period (day 1 to week 72) and follow up period (through EOS ~week 84) | — |
Countries
Canada, Czech Republic, France, Hungary, Italy, Netherlands, Poland, Russian Federation, Serbia, Spain, United Kingdom, United States
Contacts
Public Contact215MS201 Clinical Trial Team
Biogen Idec Research Limited
Outcome results
None listed