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A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis (ASCEND in SPMS)

Primary Purpose

Secondary Progressive Multiple Sclerosis

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
natalizumab
Placebo
Sponsored by
Biogen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Secondary Progressive Multiple Sclerosis focused on measuring Natalizumab, secondary, multiple sclerosis, MS, SPMS, Tysabri

Eligibility Criteria

18 Years - 58 Years (Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria (Part 1):

  • 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.
  • SPMS defined as relapsing-remitting disease followed by progression of disability independent of or not explained by multiple sclerosis (MS) relapses for at least 2 years.
  • EDSS score of 3.0 to 6.5, inclusive.
  • Multiple Sclerosis Severity Score of 4 or higher.
  • Documented confirmed evidence of disease progression independent of clinical relapses over the 1 year prior to enrollment as defined in the Study Reference Guide.

Key Exclusion Criteria (Part 1):

  • Relapsing remitting multiple sclerosis (RRMS) or primary progressive MS as defined by the revised McDonald Committee criteria.
  • Clinical relapse (within 3 months) prior to randomization.
  • T25FW test of >30 seconds during the screening period.
  • Any value below the lower limit of normal for blood levels of leukocytes, lymphocytes, or neutrophils.
  • Considered by the Investigator to be immunocompromised based on medical history, physical examination, laboratory testing, or any other testing required by local guidelines, or due to prior immunosuppressive or immunomodulating treatment.
  • Subjects for whom MRI is contraindicated (i.e., have pacemakers or other contraindicated implanted metal devices, are allergic to gadolinium, or have claustrophobia that cannot be medically managed).
  • History of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic (other than MS), dermatologic, psychiatric, and renal, or other major disease that would preclude participation in a clinical study.
  • History of malignant disease, including solid tumors and hematologic malignancies (with the exception of basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured).
  • Known history of or positive test result for human immunodeficiency virus.
  • Positive test result for hepatitis C virus (test for hepatitis C virus antibody or hepatitis B virus (test for hepatitis B surface antigen and/or hepatitis B core antibody).
  • History of transplantation or any anti-rejection therapy.
  • Presence of any infectious disease (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days prior to screening.
  • History of progressive multifocal leukoencephalopathy or other opportunistic infections.

Treatment History (Part 1)

  • Any prior treatment with cell-depleting therapies, including total lymphoid irradiation, cladribine, rituximab, alemtuzumab, or bone marrow ablation.
  • Any prior treatment with natalizumab.
  • Treatment with mitoxantrone, cyclophosphamide, cyclosporine, azathioprine, methotrexate, mycophenolate mofetil, T cell or T cell receptor vaccination, fingolimod, daclizumab, or cytapheresis within 6 months prior to randomization.
  • Treatment with intravenous or oral corticosteroids, intravenous immunoglobulin, or plasmapheresis for treatment of MS within the 3 months prior to randomization.
  • Treatment with glatiramer acetate or any interferon beta preparations within 4 weeks prior to randomization.
  • Treatment with 4-aminopyridine 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.

Key Inclusion Criteria (Part 2):

  • Subjects must have participated in and completed Part 1 per protocol, and have documented assessment attempts for EDSS, T25FW, and 9HPT prior to first open-label dosing.

Key Exclusion Criteria (Part 2):

  • Subjects with any significant change in clinical status, including laboratory tests that, in the opinion of the Investigator, would make them unsuitable to participate in this extension study. The Investigator must re-review the subject's medical fitness for participation and consider any diseases that would preclude treatment.
  • Subjects who discontinued study treatment in Part 1 OR had fewer than 20 infusions in Part 1 OR missed 2 or more consecutive infusions in Part 1.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

natalizumab

Placebo

Arm Description

In Part 1 participants were randomized to receive 300 mg of natalizumab intravenously (IV) every 4 weeks for 96 weeks. In Part 2 participants transitioned to receive open-label natalizumab 300 mg IV every 4 weeks for at least 96 weeks.

In Part 1 participants were randomized to receive placebo IV every 4 weeks for 96 weeks. In Part 2 participants transitioned to receive open-label natalizumab 300 mg IV every 4 weeks for at least 96 weeks.

Outcomes

Primary Outcome Measures

Part 1: Percentage of Participants With Confirmed Progression of Disability in One or More of the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), or 9-Hole Peg Test (9HPT)
Confirmed disability progression, defined as ≥1 of the following criteria (confirmed at a second visit ≥6 months later and at Week 96): Confirmed progression in EDSS (EDSS score increased from baseline [BL] by ≥1 point if BL EDSS ≤5.5 or by ≥0.5 points if BL EDSS ≥6); Confirmed progression in T25FW (T25FW increased by ≥20% of the BL walk); Confirmed progression in 9HPT (9HPT increased by ≥20% of the time taken at BL on either hand and confirmed on the same hand). The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. The T25FW is a quantitative mobility and leg function performance test where the participant is timed while walking for 25 feet. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs. The 95% confidence interval (CI) of the percentage is based on normal approximation.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE: any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigator, placed the participant at immediate risk of death (a life-threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect. An SAE may have also been any other medically important event in the opinion of the Investigator.

Secondary Outcome Measures

Part 1: Percentage of Participants With a T25FW Response
T25FW response is defined as any improvement from the best pre-dose T25FW in at least 75% of the scheduled on-treatment visits through Week 96. The T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet. The participant is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The time is calculated from the initiation of the instruction to start and ends when the participant has reached the 25-foot mark. The task is immediately administered again by having the patient walk back the same distance. The score for the T25FW is the average of the 2 completed trials. The 95% CI of the percentage is based on normal approximation.
Part 1: Change From Baseline in the 12-Item MS Walking Scale (MSWS-12)
MSWS-12 is a participant self-assessment of the walking limitations due to MS during the past 2 weeks. It contains 12 items that measure the impact of MS on walking. Items are summed to generate a total score and transformed to a scale with a range of 0 to 100, where higher scores indicate greater impact on walking. A negative number on change from BL value indicates an improvement in MSWS-12.
Part 1: Change From Baseline in Manual Ability Score Based on the ABILHAND Questionnaire
The ABILHAND Questionnaire measures the participant's perceived difficulty in performing everyday manual activities in the last 3 months. The participant completes a 56-item questionnaire by estimating their own difficulty or ease in performing each of 56 activities. Items are summed to generate a total score and transformed to a scale with a range of 0 to 100, where high scores indicate greater impact on manual ability. A positive number on change from baseline value indicates an improvement in ABILHAND.
Part 1: Change From Baseline in the Multiple Sclerosis Impact Scale-29 Physical (MSIS-29 Physical) Score
The 29-item MSIS-29 is a participant-reported outcome measure to assess the impact of MS on day-to-day life during the past 2 weeks from a participant's perspective; it measures 20 physical items and 9 psychological items. The physical score is generated by summing individual items and then transforming to a scale with a range of 0 to 100, where high scores indicate worse health. A negative number on change from baseline value indicates an improvement in MSIS-29.
Part 1: Percentage Change From Week 24 in Whole Brain Volume at Week 96
Whole brain volume as measured by MRI.
Part 1: Percentage of Participants Defined as Confirmed Progressors on EDSS Functional System Scores
The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. Participants with confirmed progression of disability in EDSS physical functional system scores will be defined as those who met one of the following criteria: an increase of ≥ 1 point from baseline system score of ≥ 1 or an increase of ≥ 2 points from baseline system score of 0 in at least 2 physical functional systems, or an increase of ≥ 2 points from baseline system score of ≥ 1 or an increase of ≥ 3 points from baseline system score of 0 in any 1 physical functional system. A confirmed progressor was defined as a participant who met the criteria for disability progression at any given visit and at the 6-Month Confirmation Visit. The 95% CIs are based on normal approximation.
Part 2: Percentage of Participants With Disability Worsening at 156 Weeks
Percentage of participants with disability worsening at each scheduled efficacy visit in Part 2, defined as one or more of the following: • ≥ 20% worsening from Part 1 baseline in T25FW; • ≥ 20% worsening from Part 1 baseline in 9HPT; • Worsening from Part 1 baseline in EDSS (≥ 1 point increase if Part 1 baseline EDSS ≤ 5.5 or ≥ 0.5 point increase if Part 1 baseline EDSS > 5.5). The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. The T25FW is a quantitative mobility and leg function performance test where the participant is timed while walking for 25 feet. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs. 95% CIs of percentages are based on normal approximation.
Part 2: Absolute Change From Baseline (Part 1) in T25FW
The T25FW is a quantitative mobility and leg function performance test based on a timed 25-foot walk. The participant is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The time is calculated from the initiation of the instruction to start and ends when the participant has reached the 25-foot mark. The task is immediately repeated; the score for the T25FW is the average of the two completed trials. Lower scores on time taken to reach 25 foot mark reflect a better outcome. Values are presented for the overall group, as well as the Confirmed Progressor (CP, defined in the primary outcome measure description above) and Non-Progressor (NP) subgroups.
Part 2: Percentage Change From Baseline (Part 1) in T25FW
The T25FW is a quantitative mobility and leg function performance test based on a timed 25-foot walk. The participant is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The time is calculated from the initiation of the instruction to start and ends when the participant has reached the 25-foot mark. The task is immediately repeated; the score for the T25FW is the average of the two completed trials. Values are presented for the overall group, as well as the CP (defined in the primary outcome measure description above) and NP subgroups.
Part 2: Absolute Change From Baseline (Part 1) in 9HPT (Dominant Hand)
The 9HPT is a brief, standardized, quantitative test of upper extremity function. The participant picks up 9 pegs puts them in a block containing nine empty holes, and, once they are in the holes, removes them again as quickly as possible one at a time. The total time to complete the task is recorded. Two consecutive trials with the dominant hand are immediately followed by two consecutive trials with the non-dominant hand. The two trials for each hand are averaged. Values are presented for the overall group, as well as the CP (defined in the primary outcome measure description above) and NP subgroups.
Part 2: Percentage Change From Baseline (Part 1) in 9HPT (Dominant Hand)
The 9HPT is a brief, standardized, quantitative test of upper extremity function. The participant picks up 9 pegs puts them in a block containing nine empty holes, and, once they are in the holes, removes them again as quickly as possible one at a time. The total time to complete the task is recorded. Two consecutive trials with the dominant hand are immediately followed by two consecutive trials with the non-dominant hand. The two trials for each hand are averaged. Values are presented for the overall group, as well as the CP (defined in the primary outcome measure description above) and NP subgroups.
Part 2: Absolute Change From Baseline (Part 1) in 9HPT (Non-Dominant Hand)
The 9HPT is a brief, standardized, quantitative test of upper extremity function. The participant picks up 9 pegs puts them in a block containing nine empty holes, and, once they are in the holes, removes them again as quickly as possible one at a time. The total time to complete the task is recorded. Two consecutive trials with the dominant hand are immediately followed by two consecutive trials with the non-dominant hand. The two trials for each hand are averaged. Values are presented for the overall group, as well as the CP (defined in the primary outcome measure description above) and NP subgroups.
Part 2: Percentage Change From Baseline (Part 1) in 9HPT (Non-Dominant Hand)
The 9HPT is a brief, standardized, quantitative test of upper extremity function. The participant picks up 9 pegs puts them in a block containing nine empty holes, and, once they are in the holes, removes them again as quickly as possible one at a time. The total time to complete the task is recorded. Two consecutive trials with the dominant hand are immediately followed by two consecutive trials with the non-dominant hand. The two trials for each hand are averaged. Values are presented for the overall group, as well as the CP (defined in the primary outcome measure description above) and NP subgroups.
Part 2: Absolute Change From Baseline (Part 1) in EDSS
The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. Values are presented for the overall group, as well as the CP (defined in the primary outcome measure description above) and NP subgroups.
Part 2: Percentage Change From Baseline (Part 1) in EDSS
The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. Values are presented for the overall group, as well as the CP (defined in the primary outcome measure description above) and NP subgroups.
Part 2: Absolute Change From Baseline (Part 1) in the 6-Minute Walk Test (6MWT)
The 6MWT measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes.
Part 2: Percentage Change From Baseline (Part 1) in the 6MWT
The 6MWT measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes.
Part 2: Absolute Change From Baseline (Part 1) in the MSIS-29 Physical Score
The 29-item MSIS-29 is a patient-reported outcome measure to assess the impact of MS on day-to-day life during the past 2 weeks from a patient's perspective; it measures 20 physical items and 9 psychological items. The physical score is generated by summing individual items and then transforming to a scale with a range of 0 to 100, where high scores indicate worse health. A negative number on change from baseline value indicates an improvement in MSIS-29.
Part 2: Percentage Change From Baseline (Part 1) in the MSIS-29 Physical Score
The 29-item MSIS-29 is a patient-reported outcome measure to assess the impact of MS on day-to-day life during the past 2 weeks from a patient's perspective; it measures 20 physical items and 9 psychological items. The physical score is generated by summing individual items and then transforming to a scale with a range of 0 to 100, where high scores indicate worse health. A negative number on change from baseline value indicates an improvement in MSIS-29.
Part 2: Absolute Change From Baseline (Part 1) in the Symbol Digit Modalities Test (SDMT)
SDMT is a screening test for cognitive impairment. Participants are given 90 seconds in which to pair specific numbers with given geometric figures using a key. Scores range from 0 to 110 (best).
Part 2: Percentage Change From Baseline (Part 1) in the SDMT
SDMT is a screening test for cognitive impairment. Participants are given 90 seconds in which to pair specific numbers with given geometric figures using a key. Scores range from 0 to 110 (best).
Part 2: Absolute Change From Baseline (Part 2) in the Work Productivity and Activity Impairment - Multiple Sclerosis (WPAI-MS) Questionnaire
The WPAI questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: 1. Absenteeism (percentage of work time missed) 2. Presenteesism (percentage of impairment at work/reduced on-the-job effectiveness) 3. Work productivity loss (percentage of overall work impairment [absenteeism plus presenteeism]) 4. Activity Impairment (percentage of overall activity impairment). WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.
Part 2: Percentage Change From Baseline (Part 2) in the WPAI-MS Questionnaire
The WPAI questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: 1. Absenteeism (percentage of work time missed) 2. Presenteesism (percentage of impairment at work/reduced on-the-job effectiveness) 3. Work productivity loss (WPL; percentage of overall work impairment [absenteeism plus presenteeism]) 4. Activity Impairment (AI; percentage of overall activity impairment). WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.
Part 2: Percentage Change From Week 24 (Part 1) in Whole Brain Volume
Whole brain volume as measured by MRI.
Part 2: Percentage Change From Baseline (Part 1) in Whole Gray Matter Brain Volume
Whole grey matter brain volume as measured by MRI.
Part 2: Summary of New/Enlarging T2 Lesion Counts
New or enlarging T2 lesions as measured by MRI.
Part 2: Percentage Change From Baseline (Part 1) in Number of New/Enlarging T2 Lesions
New or enlarging T2 lesions as measured by MRI.

Full Information

First Posted
July 21, 2011
Last Updated
August 10, 2017
Sponsor
Biogen
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1. Study Identification

Unique Protocol Identification Number
NCT01416181
Brief Title
A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis
Acronym
ASCEND in SPMS
Official Title
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy of Natalizumab on Reducing Disability Progression in Subjects With Secondary Progressive Multiple Sclerosis, With Optional Open-Label Extension
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Terminated
Why Stopped
The ASCEND Study did not achieve statistical significance on the primary or secondary endpoints.
Study Start Date
September 13, 2011 (Actual)
Primary Completion Date
July 28, 2015 (Actual)
Study Completion Date
April 13, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a Phase 3b, multicenter, international study conducted in 2 parts. Upon completion of the placebo-controlled period (Part 1), participants will have the option of enrolling in a 2-year open-label extension (Part 2). Part 1: The primary objective of the study is to investigate whether treatment with natalizumab slows the accumulation of disability not related to relapses in participants with secondary progressive multiple sclerosis (SPMS). The secondary objectives of Part 1 of this study are to determine the proportion of participants with consistent improvement in Timed 25-Foot Walk (T25FW), the change in participant-reported ambulatory status as measured by the 12-item MS Walking Scale (MSWS-12), the change in manual ability based on the ABILHAND Questionnaire, the impact of natalizumab on participant-reported quality of life using the Multiple Sclerosis Impact Scale-29 Physical (MSIS-29 Physical), the change in whole brain volume between the end of study and Week 24 using magnetic resonance imaging (MRI) and the proportion of participants experiencing progression of disability as measured by individual physical Expanded Disability Status Scale (EDSS) system scores. Part 2: The primary objective of Part 2 of the study is to evaluate the safety profile of natalizumab in participants with SPMS. The secondary objectives of Part 2 of the study are to investigate long-term disability (based on clinical or participant-reported assessments) in participants with SPMS receiving natalizumab treatment for approximately 4 years and to assess change in brain volume and T2 lesion volume.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Secondary Progressive Multiple Sclerosis
Keywords
Natalizumab, secondary, multiple sclerosis, MS, SPMS, Tysabri

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
889 (Actual)

8. Arms, Groups, and Interventions

Arm Title
natalizumab
Arm Type
Experimental
Arm Description
In Part 1 participants were randomized to receive 300 mg of natalizumab intravenously (IV) every 4 weeks for 96 weeks. In Part 2 participants transitioned to receive open-label natalizumab 300 mg IV every 4 weeks for at least 96 weeks.
Arm Title
Placebo
Arm Type
Experimental
Arm Description
In Part 1 participants were randomized to receive placebo IV every 4 weeks for 96 weeks. In Part 2 participants transitioned to receive open-label natalizumab 300 mg IV every 4 weeks for at least 96 weeks.
Intervention Type
Drug
Intervention Name(s)
natalizumab
Other Intervention Name(s)
Tysabri, BG00002
Intervention Description
Administered as specified in the treatment arm
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matched placebo in part 1
Primary Outcome Measure Information:
Title
Part 1: Percentage of Participants With Confirmed Progression of Disability in One or More of the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), or 9-Hole Peg Test (9HPT)
Description
Confirmed disability progression, defined as ≥1 of the following criteria (confirmed at a second visit ≥6 months later and at Week 96): Confirmed progression in EDSS (EDSS score increased from baseline [BL] by ≥1 point if BL EDSS ≤5.5 or by ≥0.5 points if BL EDSS ≥6); Confirmed progression in T25FW (T25FW increased by ≥20% of the BL walk); Confirmed progression in 9HPT (9HPT increased by ≥20% of the time taken at BL on either hand and confirmed on the same hand). The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. The T25FW is a quantitative mobility and leg function performance test where the participant is timed while walking for 25 feet. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs. The 95% confidence interval (CI) of the percentage is based on normal approximation.
Time Frame
Up to 96 weeks (2 years)
Title
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
AE: any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigator, placed the participant at immediate risk of death (a life-threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect. An SAE may have also been any other medically important event in the opinion of the Investigator.
Time Frame
218 weeks
Secondary Outcome Measure Information:
Title
Part 1: Percentage of Participants With a T25FW Response
Description
T25FW response is defined as any improvement from the best pre-dose T25FW in at least 75% of the scheduled on-treatment visits through Week 96. The T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet. The participant is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The time is calculated from the initiation of the instruction to start and ends when the participant has reached the 25-foot mark. The task is immediately administered again by having the patient walk back the same distance. The score for the T25FW is the average of the 2 completed trials. The 95% CI of the percentage is based on normal approximation.
Time Frame
Up to 96 weeks
Title
Part 1: Change From Baseline in the 12-Item MS Walking Scale (MSWS-12)
Description
MSWS-12 is a participant self-assessment of the walking limitations due to MS during the past 2 weeks. It contains 12 items that measure the impact of MS on walking. Items are summed to generate a total score and transformed to a scale with a range of 0 to 100, where higher scores indicate greater impact on walking. A negative number on change from BL value indicates an improvement in MSWS-12.
Time Frame
Baseline and Week 96
Title
Part 1: Change From Baseline in Manual Ability Score Based on the ABILHAND Questionnaire
Description
The ABILHAND Questionnaire measures the participant's perceived difficulty in performing everyday manual activities in the last 3 months. The participant completes a 56-item questionnaire by estimating their own difficulty or ease in performing each of 56 activities. Items are summed to generate a total score and transformed to a scale with a range of 0 to 100, where high scores indicate greater impact on manual ability. A positive number on change from baseline value indicates an improvement in ABILHAND.
Time Frame
Baseline and Week 96
Title
Part 1: Change From Baseline in the Multiple Sclerosis Impact Scale-29 Physical (MSIS-29 Physical) Score
Description
The 29-item MSIS-29 is a participant-reported outcome measure to assess the impact of MS on day-to-day life during the past 2 weeks from a participant's perspective; it measures 20 physical items and 9 psychological items. The physical score is generated by summing individual items and then transforming to a scale with a range of 0 to 100, where high scores indicate worse health. A negative number on change from baseline value indicates an improvement in MSIS-29.
Time Frame
Baseline and Week 96
Title
Part 1: Percentage Change From Week 24 in Whole Brain Volume at Week 96
Description
Whole brain volume as measured by MRI.
Time Frame
Week 24 and Week 96
Title
Part 1: Percentage of Participants Defined as Confirmed Progressors on EDSS Functional System Scores
Description
The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. Participants with confirmed progression of disability in EDSS physical functional system scores will be defined as those who met one of the following criteria: an increase of ≥ 1 point from baseline system score of ≥ 1 or an increase of ≥ 2 points from baseline system score of 0 in at least 2 physical functional systems, or an increase of ≥ 2 points from baseline system score of ≥ 1 or an increase of ≥ 3 points from baseline system score of 0 in any 1 physical functional system. A confirmed progressor was defined as a participant who met the criteria for disability progression at any given visit and at the 6-Month Confirmation Visit. The 95% CIs are based on normal approximation.
Time Frame
Up to 96 weeks
Title
Part 2: Percentage of Participants With Disability Worsening at 156 Weeks
Description
Percentage of participants with disability worsening at each scheduled efficacy visit in Part 2, defined as one or more of the following: • ≥ 20% worsening from Part 1 baseline in T25FW; • ≥ 20% worsening from Part 1 baseline in 9HPT; • Worsening from Part 1 baseline in EDSS (≥ 1 point increase if Part 1 baseline EDSS ≤ 5.5 or ≥ 0.5 point increase if Part 1 baseline EDSS > 5.5). The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. The T25FW is a quantitative mobility and leg function performance test where the participant is timed while walking for 25 feet. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs. 95% CIs of percentages are based on normal approximation.
Time Frame
Week 156
Title
Part 2: Absolute Change From Baseline (Part 1) in T25FW
Description
The T25FW is a quantitative mobility and leg function performance test based on a timed 25-foot walk. The participant is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The time is calculated from the initiation of the instruction to start and ends when the participant has reached the 25-foot mark. The task is immediately repeated; the score for the T25FW is the average of the two completed trials. Lower scores on time taken to reach 25 foot mark reflect a better outcome. Values are presented for the overall group, as well as the Confirmed Progressor (CP, defined in the primary outcome measure description above) and Non-Progressor (NP) subgroups.
Time Frame
Baseline (Part 1) and Weeks 156, 204
Title
Part 2: Percentage Change From Baseline (Part 1) in T25FW
Description
The T25FW is a quantitative mobility and leg function performance test based on a timed 25-foot walk. The participant is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The time is calculated from the initiation of the instruction to start and ends when the participant has reached the 25-foot mark. The task is immediately repeated; the score for the T25FW is the average of the two completed trials. Values are presented for the overall group, as well as the CP (defined in the primary outcome measure description above) and NP subgroups.
Time Frame
Baseline (Part 1) and Weeks 156, 204
Title
Part 2: Absolute Change From Baseline (Part 1) in 9HPT (Dominant Hand)
Description
The 9HPT is a brief, standardized, quantitative test of upper extremity function. The participant picks up 9 pegs puts them in a block containing nine empty holes, and, once they are in the holes, removes them again as quickly as possible one at a time. The total time to complete the task is recorded. Two consecutive trials with the dominant hand are immediately followed by two consecutive trials with the non-dominant hand. The two trials for each hand are averaged. Values are presented for the overall group, as well as the CP (defined in the primary outcome measure description above) and NP subgroups.
Time Frame
Baseline (Part 1) and Weeks 156, 204
Title
Part 2: Percentage Change From Baseline (Part 1) in 9HPT (Dominant Hand)
Description
The 9HPT is a brief, standardized, quantitative test of upper extremity function. The participant picks up 9 pegs puts them in a block containing nine empty holes, and, once they are in the holes, removes them again as quickly as possible one at a time. The total time to complete the task is recorded. Two consecutive trials with the dominant hand are immediately followed by two consecutive trials with the non-dominant hand. The two trials for each hand are averaged. Values are presented for the overall group, as well as the CP (defined in the primary outcome measure description above) and NP subgroups.
Time Frame
Baseline (Part 1) and Weeks 156, 204
Title
Part 2: Absolute Change From Baseline (Part 1) in 9HPT (Non-Dominant Hand)
Description
The 9HPT is a brief, standardized, quantitative test of upper extremity function. The participant picks up 9 pegs puts them in a block containing nine empty holes, and, once they are in the holes, removes them again as quickly as possible one at a time. The total time to complete the task is recorded. Two consecutive trials with the dominant hand are immediately followed by two consecutive trials with the non-dominant hand. The two trials for each hand are averaged. Values are presented for the overall group, as well as the CP (defined in the primary outcome measure description above) and NP subgroups.
Time Frame
Baseline (Part 1) and Weeks 156, 204
Title
Part 2: Percentage Change From Baseline (Part 1) in 9HPT (Non-Dominant Hand)
Description
The 9HPT is a brief, standardized, quantitative test of upper extremity function. The participant picks up 9 pegs puts them in a block containing nine empty holes, and, once they are in the holes, removes them again as quickly as possible one at a time. The total time to complete the task is recorded. Two consecutive trials with the dominant hand are immediately followed by two consecutive trials with the non-dominant hand. The two trials for each hand are averaged. Values are presented for the overall group, as well as the CP (defined in the primary outcome measure description above) and NP subgroups.
Time Frame
Baseline (Part 1) and Weeks 156, 204
Title
Part 2: Absolute Change From Baseline (Part 1) in EDSS
Description
The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. Values are presented for the overall group, as well as the CP (defined in the primary outcome measure description above) and NP subgroups.
Time Frame
Baseline (Part 1) and Weeks 156, 204
Title
Part 2: Percentage Change From Baseline (Part 1) in EDSS
Description
The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. Values are presented for the overall group, as well as the CP (defined in the primary outcome measure description above) and NP subgroups.
Time Frame
Baseline (Part 1) and Weeks 156, 204
Title
Part 2: Absolute Change From Baseline (Part 1) in the 6-Minute Walk Test (6MWT)
Description
The 6MWT measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes.
Time Frame
Baseline (Part 1) and Weeks 156 and 204
Title
Part 2: Percentage Change From Baseline (Part 1) in the 6MWT
Description
The 6MWT measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes.
Time Frame
Baseline (Part 1) and Weeks 156, 204
Title
Part 2: Absolute Change From Baseline (Part 1) in the MSIS-29 Physical Score
Description
The 29-item MSIS-29 is a patient-reported outcome measure to assess the impact of MS on day-to-day life during the past 2 weeks from a patient's perspective; it measures 20 physical items and 9 psychological items. The physical score is generated by summing individual items and then transforming to a scale with a range of 0 to 100, where high scores indicate worse health. A negative number on change from baseline value indicates an improvement in MSIS-29.
Time Frame
Baseline (Part 1) and Weeks 156 and 204
Title
Part 2: Percentage Change From Baseline (Part 1) in the MSIS-29 Physical Score
Description
The 29-item MSIS-29 is a patient-reported outcome measure to assess the impact of MS on day-to-day life during the past 2 weeks from a patient's perspective; it measures 20 physical items and 9 psychological items. The physical score is generated by summing individual items and then transforming to a scale with a range of 0 to 100, where high scores indicate worse health. A negative number on change from baseline value indicates an improvement in MSIS-29.
Time Frame
Baseline (Part 1) and Weeks 156, 204
Title
Part 2: Absolute Change From Baseline (Part 1) in the Symbol Digit Modalities Test (SDMT)
Description
SDMT is a screening test for cognitive impairment. Participants are given 90 seconds in which to pair specific numbers with given geometric figures using a key. Scores range from 0 to 110 (best).
Time Frame
Baseline (Part 1) and every 4 weeks from Week 108 to Week 204
Title
Part 2: Percentage Change From Baseline (Part 1) in the SDMT
Description
SDMT is a screening test for cognitive impairment. Participants are given 90 seconds in which to pair specific numbers with given geometric figures using a key. Scores range from 0 to 110 (best).
Time Frame
Baseline (Part 1) and every 4 weeks from Week 108 to Week 204
Title
Part 2: Absolute Change From Baseline (Part 2) in the Work Productivity and Activity Impairment - Multiple Sclerosis (WPAI-MS) Questionnaire
Description
The WPAI questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: 1. Absenteeism (percentage of work time missed) 2. Presenteesism (percentage of impairment at work/reduced on-the-job effectiveness) 3. Work productivity loss (percentage of overall work impairment [absenteeism plus presenteeism]) 4. Activity Impairment (percentage of overall activity impairment). WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.
Time Frame
Part 2 Baseline (Week 108) and Weeks 156 and 204
Title
Part 2: Percentage Change From Baseline (Part 2) in the WPAI-MS Questionnaire
Description
The WPAI questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: 1. Absenteeism (percentage of work time missed) 2. Presenteesism (percentage of impairment at work/reduced on-the-job effectiveness) 3. Work productivity loss (WPL; percentage of overall work impairment [absenteeism plus presenteeism]) 4. Activity Impairment (AI; percentage of overall activity impairment). WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.
Time Frame
Part 2 Baseline (Week 108) and Weeks 156 and 204
Title
Part 2: Percentage Change From Week 24 (Part 1) in Whole Brain Volume
Description
Whole brain volume as measured by MRI.
Time Frame
Week 24 (Part 1) and Weeks 156 and 204
Title
Part 2: Percentage Change From Baseline (Part 1) in Whole Gray Matter Brain Volume
Description
Whole grey matter brain volume as measured by MRI.
Time Frame
Baseline (Part 1) and Weeks 156 and 204
Title
Part 2: Summary of New/Enlarging T2 Lesion Counts
Description
New or enlarging T2 lesions as measured by MRI.
Time Frame
Baseline (Part 1) up to Week 204
Title
Part 2: Percentage Change From Baseline (Part 1) in Number of New/Enlarging T2 Lesions
Description
New or enlarging T2 lesions as measured by MRI.
Time Frame
Baseline (Part 1) and Weeks 156 and 204

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
58 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria (Part 1): 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. SPMS defined as relapsing-remitting disease followed by progression of disability independent of or not explained by multiple sclerosis (MS) relapses for at least 2 years. EDSS score of 3.0 to 6.5, inclusive. Multiple Sclerosis Severity Score of 4 or higher. Documented confirmed evidence of disease progression independent of clinical relapses over the 1 year prior to enrollment as defined in the Study Reference Guide. Key Exclusion Criteria (Part 1): Relapsing remitting multiple sclerosis (RRMS) or primary progressive MS as defined by the revised McDonald Committee criteria. Clinical relapse (within 3 months) prior to randomization. T25FW test of >30 seconds during the screening period. Any value below the lower limit of normal for blood levels of leukocytes, lymphocytes, or neutrophils. Considered by the Investigator to be immunocompromised based on medical history, physical examination, laboratory testing, or any other testing required by local guidelines, or due to prior immunosuppressive or immunomodulating treatment. Subjects for whom MRI is contraindicated (i.e., have pacemakers or other contraindicated implanted metal devices, are allergic to gadolinium, or have claustrophobia that cannot be medically managed). History of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic (other than MS), dermatologic, psychiatric, and renal, or other major disease that would preclude participation in a clinical study. History of malignant disease, including solid tumors and hematologic malignancies (with the exception of basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured). Known history of or positive test result for human immunodeficiency virus. Positive test result for hepatitis C virus (test for hepatitis C virus antibody or hepatitis B virus (test for hepatitis B surface antigen and/or hepatitis B core antibody). History of transplantation or any anti-rejection therapy. Presence of any infectious disease (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days prior to screening. History of progressive multifocal leukoencephalopathy or other opportunistic infections. Treatment History (Part 1) Any prior treatment with cell-depleting therapies, including total lymphoid irradiation, cladribine, rituximab, alemtuzumab, or bone marrow ablation. Any prior treatment with natalizumab. Treatment with mitoxantrone, cyclophosphamide, cyclosporine, azathioprine, methotrexate, mycophenolate mofetil, T cell or T cell receptor vaccination, fingolimod, daclizumab, or cytapheresis within 6 months prior to randomization. Treatment with intravenous or oral corticosteroids, intravenous immunoglobulin, or plasmapheresis for treatment of MS within the 3 months prior to randomization. Treatment with glatiramer acetate or any interferon beta preparations within 4 weeks prior to randomization. Treatment with 4-aminopyridine 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. Key Inclusion Criteria (Part 2): Subjects must have participated in and completed Part 1 per protocol, and have documented assessment attempts for EDSS, T25FW, and 9HPT prior to first open-label dosing. Key Exclusion Criteria (Part 2): Subjects with any significant change in clinical status, including laboratory tests that, in the opinion of the Investigator, would make them unsuitable to participate in this extension study. The Investigator must re-review the subject's medical fitness for participation and consider any diseases that would preclude treatment. Subjects who discontinued study treatment in Part 1 OR had fewer than 20 infusions in Part 1 OR missed 2 or more consecutive infusions in Part 1. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
Research Site
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85741
Country
United States
Facility Name
Research Site
City
Fullerton
State/Province
California
ZIP/Postal Code
92835
Country
United States
Facility Name
Research Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Research Site
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Research Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Research Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Research Site
City
Lake Barrington
State/Province
Illinois
ZIP/Postal Code
60010
Country
United States
Facility Name
Research Site
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61606
Country
United States
Facility Name
Research Site
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Research Site
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46256
Country
United States
Facility Name
Research Site
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Research Site
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40513
Country
United States
Facility Name
Research Site
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
Research Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Research Site
City
Burlington
State/Province
Massachusetts
ZIP/Postal Code
01805
Country
United States
Facility Name
Research Site
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Research Site
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Research Site
City
Teaneck
State/Province
New Jersey
ZIP/Postal Code
07666
Country
United States
Facility Name
Research Site
City
Latham
State/Province
New York
ZIP/Postal Code
12110
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Research Site
City
Advance
State/Province
North Carolina
ZIP/Postal Code
27006
Country
United States
Facility Name
Research Site
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28207
Country
United States
Facility Name
Research Site
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27607
Country
United States
Facility Name
Research Site
City
Akron
State/Province
Ohio
ZIP/Postal Code
44320
Country
United States
Facility Name
Research Site
City
Uniontown
State/Province
Ohio
ZIP/Postal Code
44685
Country
United States
Facility Name
Research Site
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Research Site
City
Clackamas
State/Province
Oregon
ZIP/Postal Code
97015
Country
United States
Facility Name
Research Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97225
Country
United States
Facility Name
Research Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Research Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37215
Country
United States
Facility Name
Research Site
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Facility Name
Research Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
Facility Name
Research Site
City
Green Bay
State/Province
Wisconsin
ZIP/Postal Code
54311
Country
United States
Facility Name
Research Site
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53215
Country
United States
Facility Name
Research Site
City
La Louviere
ZIP/Postal Code
7100
Country
Belgium
Facility Name
Research Site
City
Melsbroek
ZIP/Postal Code
1820
Country
Belgium
Facility Name
Research Site
City
Overpelt
ZIP/Postal Code
3900
Country
Belgium
Facility Name
Research Site
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 2T9
Country
Canada
Facility Name
Research Site
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2G3
Country
Canada
Facility Name
Research Site
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6T 1Z3
Country
Canada
Facility Name
Research Site
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 4K4
Country
Canada
Facility Name
Research Site
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 2V7
Country
Canada
Facility Name
Research Site
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5A5
Country
Canada
Facility Name
Research Site
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Research Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
Research Site
City
Gatineau
State/Province
Quebec
ZIP/Postal Code
J9J 0A5
Country
Canada
Facility Name
Research Site
City
Greenfield Park
State/Province
Quebec
ZIP/Postal Code
J4V 2J2
Country
Canada
Facility Name
Research Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2L 4M1
Country
Canada
Facility Name
Research Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3A 2B4
Country
Canada
Facility Name
Research Site
City
Hradec Kralove
State/Province
Bohemia
ZIP/Postal Code
50005
Country
Czechia
Facility Name
Research Site
City
Brno
ZIP/Postal Code
65691
Country
Czechia
Facility Name
Research Site
City
Olomouc
ZIP/Postal Code
77520
Country
Czechia
Facility Name
Research Site
City
Praha
ZIP/Postal Code
12111
Country
Czechia
Facility Name
Research Site
City
Arthus C
ZIP/Postal Code
8000
Country
Denmark
Facility Name
Research Site
City
Esbjerg
ZIP/Postal Code
6700
Country
Denmark
Facility Name
Research Site
City
Glostrup
ZIP/Postal Code
2600
Country
Denmark
Facility Name
Research Site
City
København Ø
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Research Site
City
Odense
ZIP/Postal Code
5000
Country
Denmark
Facility Name
Research Site
City
Jyväskylä
ZIP/Postal Code
40620
Country
Finland
Facility Name
Research Site
City
Tampere
ZIP/Postal Code
33520
Country
Finland
Facility Name
Research Site
City
Turku
ZIP/Postal Code
20520
Country
Finland
Facility Name
Research Site
City
Nice
State/Province
Alpes Maritimes
ZIP/Postal Code
06002
Country
France
Facility Name
Research Site
City
Marseille cedex 5
State/Province
Bouches-du-Rhône
ZIP/Postal Code
13385
Country
France
Facility Name
Research Site
City
Nantes
State/Province
Loire Atlantique
ZIP/Postal Code
44093
Country
France
Facility Name
Research Site
City
Nancy
State/Province
Meurthe et Moselle
ZIP/Postal Code
54035
Country
France
Facility Name
Research Site
City
Lille Cedex
State/Province
Nord
ZIP/Postal Code
59000
Country
France
Facility Name
Research Site
City
Bron cedex
State/Province
Rhone
ZIP/Postal Code
69677
Country
France
Facility Name
Research Site
City
Salouel
State/Province
Somme
ZIP/Postal Code
80054
Country
France
Facility Name
Research Site
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Research Site
City
Bad Wilbad
State/Province
Baden Wuerttemberg
ZIP/Postal Code
75323
Country
Germany
Facility Name
Research Site
City
Tuebingen
State/Province
Baden Wuerttemberg
ZIP/Postal Code
72076
Country
Germany
Facility Name
Research Site
City
Bad Mergentheim
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
97980
Country
Germany
Facility Name
Research Site
City
Muenchen
State/Province
Bayern
ZIP/Postal Code
81377
Country
Germany
Facility Name
Research Site
City
Muenchen
State/Province
Bayern
ZIP/Postal Code
81675
Country
Germany
Facility Name
Research Site
City
Hennigsdorf
State/Province
Brandenburg
ZIP/Postal Code
16761
Country
Germany
Facility Name
Research Site
City
Teupitz
State/Province
Brandenburg
ZIP/Postal Code
15755
Country
Germany
Facility Name
Research Site
City
Kassel
State/Province
Hessen
ZIP/Postal Code
34121
Country
Germany
Facility Name
Research Site
City
Duesseldorf
State/Province
Nordrhein Westfalen
ZIP/Postal Code
40225
Country
Germany
Facility Name
Research Site
City
Muenster
State/Province
Nordrhein Westfalen
ZIP/Postal Code
48149
Country
Germany
Facility Name
Research Site
City
Dresden
State/Province
Sachsen
ZIP/Postal Code
01307
Country
Germany
Facility Name
Research Site
City
Dublin
ZIP/Postal Code
D4
Country
Ireland
Facility Name
Research Site
City
Dublin
ZIP/Postal Code
D9
Country
Ireland
Facility Name
Research Site
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Facility Name
Research Site
City
Ramat Gan
ZIP/Postal Code
52621
Country
Israel
Facility Name
Research Site
City
Baggiovara
State/Province
Modena
ZIP/Postal Code
41100
Country
Italy
Facility Name
Research Site
City
Cefalu
State/Province
Palermo
ZIP/Postal Code
90015
Country
Italy
Facility Name
Research Site
City
Gallarate
State/Province
Varese
ZIP/Postal Code
21013
Country
Italy
Facility Name
Research Site
City
Bari
ZIP/Postal Code
70124
Country
Italy
Facility Name
Research Site
City
Florence
ZIP/Postal Code
50134
Country
Italy
Facility Name
Research Site
City
Genova
ZIP/Postal Code
16132
Country
Italy
Facility Name
Research Site
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
Research Site
City
Milano
ZIP/Postal Code
20132
Country
Italy
Facility Name
Research Site
City
Naples
ZIP/Postal Code
80138
Country
Italy
Facility Name
Research Site
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Research Site
City
Palermo
ZIP/Postal Code
90146
Country
Italy
Facility Name
Research Site
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Research Site
City
Rome
ZIP/Postal Code
00176
Country
Italy
Facility Name
Research Site
City
Rome
ZIP/Postal Code
00189
Country
Italy
Facility Name
Research Site
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
Research Site
City
Breda
ZIP/Postal Code
4800 RK
Country
Netherlands
Facility Name
Research Site
City
Hertogenbosch
ZIP/Postal Code
5223 GZ
Country
Netherlands
Facility Name
Research Site
City
Hoorn
ZIP/Postal Code
1624 NP
Country
Netherlands
Facility Name
Research Site
City
Nieuwegein
ZIP/Postal Code
3430 EM
Country
Netherlands
Facility Name
Research Site
City
Sittard-Geleen
ZIP/Postal Code
6130 MB
Country
Netherlands
Facility Name
Research Site
City
Bialystok
ZIP/Postal Code
15-276
Country
Poland
Facility Name
Research Site
City
Gdansk
ZIP/Postal Code
80-803
Country
Poland
Facility Name
Research Site
City
Katowice
ZIP/Postal Code
40-595
Country
Poland
Facility Name
Research Site
City
Katowice
ZIP/Postal Code
40-635
Country
Poland
Facility Name
Research Site
City
Katowice
ZIP/Postal Code
40-749
Country
Poland
Facility Name
Research Site
City
Krakow
ZIP/Postal Code
31-505
Country
Poland
Facility Name
Research Site
City
Lodz
ZIP/Postal Code
90-324
Country
Poland
Facility Name
Research Site
City
Lublin
ZIP/Postal Code
20-954
Country
Poland
Facility Name
Research Site
City
Olsztyn
ZIP/Postal Code
10-561
Country
Poland
Facility Name
Research Site
City
Plewiska
ZIP/Postal Code
62-064
Country
Poland
Facility Name
Research Site
City
Poznan
ZIP/Postal Code
61-853
Country
Poland
Facility Name
Research Site
City
Szczecin
ZIP/Postal Code
70-111
Country
Poland
Facility Name
Research Site
City
Warszawa-Miedzylesie
ZIP/Postal Code
04-749
Country
Poland
Facility Name
Research Site
City
Warszawa
ZIP/Postal Code
01-697
Country
Poland
Facility Name
Research Site
City
Warszawa
ZIP/Postal Code
02-097
Country
Poland
Facility Name
Research Site
City
Warszawa
ZIP/Postal Code
04-141
Country
Poland
Facility Name
Research Site
City
Wroclaw
ZIP/Postal Code
50-556
Country
Poland
Facility Name
Research Site
City
Belgorod
ZIP/Postal Code
308007
Country
Russian Federation
Facility Name
Research Site
City
Kazan
ZIP/Postal Code
420021
Country
Russian Federation
Facility Name
Research Site
City
Kazan
ZIP/Postal Code
420097
Country
Russian Federation
Facility Name
Research Site
City
Moscow
ZIP/Postal Code
127015
Country
Russian Federation
Facility Name
Research Site
City
St. Petersburg
ZIP/Postal Code
197110
Country
Russian Federation
Facility Name
Research Site
City
Tyumen
ZIP/Postal Code
625000
Country
Russian Federation
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
Research Site
City
El Palmar
ZIP/Postal Code
30120
Country
Spain
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Research Site
City
Majadahonda
ZIP/Postal Code
28222
Country
Spain
Facility Name
Research Site
City
Málaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Research Site
City
Santa Cruz de Tenerife
ZIP/Postal Code
38010
Country
Spain
Facility Name
Research Site
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
Facility Name
Research Site
City
Göteborg
ZIP/Postal Code
41345
Country
Sweden
Facility Name
Research Site
City
Stockholm
ZIP/Postal Code
14186
Country
Sweden
Facility Name
Research Site
City
Stockholm
ZIP/Postal Code
17176
Country
Sweden
Facility Name
Research Site
City
Stockholm
ZIP/Postal Code
18288
Country
Sweden
Facility Name
Research Site
City
Umeå
ZIP/Postal Code
90185
Country
Sweden
Facility Name
Research Site
City
Örebro
ZIP/Postal Code
70185
Country
Sweden
Facility Name
Research Site
City
Irvine
State/Province
Ayrshire
ZIP/Postal Code
KA12 8SS
Country
United Kingdom
Facility Name
Research Site
City
Edgbaston
State/Province
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Facility Name
Research Site
City
Exeter
State/Province
Devon
ZIP/Postal Code
EX2 5DW
Country
United Kingdom
Facility Name
Research Site
City
Plymouth
State/Province
Devon
ZIP/Postal Code
PL6 8BX
Country
United Kingdom
Facility Name
Research Site
City
London
State/Province
Greater London
ZIP/Postal Code
E1 2AT
Country
United Kingdom
Facility Name
Research Site
City
London
State/Province
Greater London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Facility Name
Research Site
City
Hammersmith
State/Province
London
ZIP/Postal Code
W6 8RF
Country
United Kingdom
Facility Name
Research Site
City
Edinburgh
State/Province
Lothian Region
ZIP/Postal Code
EH4 2XU
Country
United Kingdom
Facility Name
Research Site
City
Salford
State/Province
Manchester
ZIP/Postal Code
M6 8HD
Country
United Kingdom
Facility Name
Research Site
City
Liverpool
State/Province
Merseyside
ZIP/Postal Code
L9 7LJ
Country
United Kingdom
Facility Name
Research Site
City
Norwich
State/Province
Norfolk
ZIP/Postal Code
NR4 7UY
Country
United Kingdom
Facility Name
Research Site
City
Nottingham
State/Province
Nottinghamshire
ZIP/Postal Code
NG7 2UH
Country
United Kingdom
Facility Name
Research Site
City
Morriston
State/Province
Swansea
ZIP/Postal Code
SA6 6NL
Country
United Kingdom
Facility Name
Research Site
City
Newcastle
State/Province
Tyne
ZIP/Postal Code
NE1 4LP
Country
United Kingdom
Facility Name
Research Site
City
Brighton
ZIP/Postal Code
BN2 5BE
Country
United Kingdom
Facility Name
Research Site
City
London
ZIP/Postal Code
WC1N 3BG
Country
United Kingdom
Facility Name
Research Site
City
Sheffield
ZIP/Postal Code
S10 2JF
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
35720980
Citation
Beynon V, George IC, Elliott C, Arnold DL, Ke J, Chen H, Zhu L, Ke C, Giovannoni G, Scaramozza M, Campbell N, Bradley DP, Franchimont N, Gafson A, Belachew S. Chronic lesion activity and disability progression in secondary progressive multiple sclerosis. BMJ Neurol Open. 2022 Jun 7;4(1):e000240. doi: 10.1136/bmjno-2021-000240. eCollection 2022.
Results Reference
derived
PubMed Identifier
34376508
Citation
Koch MW, Mostert J, Zhang Y, Wolinsky JS, Lublin FD, Strijbis E, Cutter G. Association of Age With Contrast-Enhancing Lesions Across the Multiple Sclerosis Disease Spectrum. Neurology. 2021 Sep 28;97(13):e1334-e1342. doi: 10.1212/WNL.0000000000012603. Epub 2021 Aug 10.
Results Reference
derived
PubMed Identifier
29545067
Citation
Kapoor R, Ho PR, Campbell N, Chang I, Deykin A, Forrestal F, Lucas N, Yu B, Arnold DL, Freedman MS, Goldman MD, Hartung HP, Havrdova EK, Jeffery D, Miller A, Sellebjerg F, Cadavid D, Mikol D, Steiner D; ASCEND investigators. Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND): a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension. Lancet Neurol. 2018 May;17(5):405-415. doi: 10.1016/S1474-4422(18)30069-3. Epub 2018 Mar 12.
Results Reference
derived
Links:
URL
http://www.tysabri.com
Description
Find out what to expect with TYSABRI MS treatment

Learn more about this trial

A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis

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