A study to assess the safety and efficacy of BIIB033 in patients with relapsing forms of multiple sclerosis when used concurrently with Avonex®

• Register: EUCTR
• Last refreshed on: 4 July 2016
• Main ID: EUCTR2011-006262-40-CZ
• Date of registration: 05/04/2013
• Prospective Registration: Yes
• Primary sponsor: Biogen Idec Research Limited
• Public title: A study to assess the safety and efficacy of BIIB033 in patients with relapsing forms of multiple sclerosis when used concurrently with Avonex®
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Subjects with Relapsing Forms of Multiple Sclerosis When Used Concurrently with Avonex®
• Date of first enrolment: 18/06/2013
• Target sample size: 396
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-006262-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 5
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Czech Republic, France, Hungary, Italy, Netherlands, Poland, Russian Federation, Serbia, Spain, United Kingdom, United States

Contacts

• Name: 215MS201 Clinical Trial Team
• Affiliation: Biogen Idec Research Limited

• Name: 215MS201 Clinical Trial Team
• Affiliation: Biogen Idec Research Limited

Key inclusion & exclusion 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:
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

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

Health Condition(s) or Problem(s) studied

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

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

Intervention(s)

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: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Avonex
Product Name: AVONEX
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Interferon beta-1a
CAS Number: 145258-61-3
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 30-

Primary Outcome(s)

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.

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).

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.

Timepoint(s) of evaluation of this end point: Quarterly over 72 weeks

Secondary Outcome(s)

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)

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

Secondary ID(s)

215MS201

Source(s) of Monetary Support

Biogen Idec Research Limited