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TerminatedNCT01416181ASCEND in SPMSUpdated Sep 11, 2017Results posted

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

A Phase 3 interventional study of natalizumab and Placebo in Secondary Progressive Multiple Sclerosis, sponsored by Biogen. Terminated at 161 sites in 17 countries. Open to participants aged 18 Years to 58 Years. Per ClinicalTrials.gov, last updated 2017-09-11.

Sponsored by Biogen · Phase 3, Interventional, and Treatment

Why this study was terminated
The ASCEND Study did not achieve statistical significance on the primary or secondary endpoints.
Phase
Phase 3
Study type
Interventional
Enrollment
889
Allocation
Randomized
Ages
18 Years to 58 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Secondary Progressive Multiple Sclerosis

Keywords

  • Natalizumab
  • secondary
  • multiple sclerosis
  • MS
  • SPMS
  • Tysabri
03

In context

Neoplasm Metastasis

3,514 studies on the registry are indexed under Neoplasm Metastasis; 883 are open to participants now.

This study's enrollment of 889 is above the median of 54 across 2,765 interventional studies indexed under Neoplasm Metastasis.

Browse Neoplasm Metastasis studies →

Lead sponsor

Biogen is the lead sponsor of 494 studies on the registry; 22 are open to participants now.

Of its 98 completed or terminated interventional studies of FDA-regulated products, 49 (50%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 58 Years
Sexes eligible
All
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.

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
889 participants (actual)

Study arms

  • Experimental
    natalizumab

    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.

    Drug: natalizumab

  • Experimental
    Placebo

    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.

    Drug: natalizumab · Drug: Placebo

Interventions

  • Drugnatalizumab

    Administered as specified in the treatment arm

    Also known as: Tysabri, BG00002

  • DrugPlacebo

    Matched placebo in part 1

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Up to 96 weeks (2 years)

  2. 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.

    Time frame: 218 weeks

Secondary outcomes

  1. 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.

    Time frame: Up to 96 weeks

  2. 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.

    Time frame: Baseline and Week 96

  3. 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.

    Time frame: Baseline and Week 96

  4. 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.

    Time frame: Baseline and Week 96

  5. Part 1: Percentage Change From Week 24 in Whole Brain Volume at Week 96

    Whole brain volume as measured by MRI.

    Time frame: Week 24 and Week 96

  6. 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.

    Time frame: Up to 96 weeks

  7. 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.

    Time frame: Week 156

  8. 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.

    Time frame: Baseline (Part 1) and Weeks 156, 204

  9. 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.

    Time frame: Baseline (Part 1) and Weeks 156, 204

  10. 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.

    Time frame: Baseline (Part 1) and Weeks 156, 204

  11. 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.

    Time frame: Baseline (Part 1) and Weeks 156, 204

  12. 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.

    Time frame: Baseline (Part 1) and Weeks 156, 204

  13. 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.

    Time frame: Baseline (Part 1) and Weeks 156, 204

  14. 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.

    Time frame: Baseline (Part 1) and Weeks 156, 204

  15. 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.

    Time frame: Baseline (Part 1) and Weeks 156, 204

  16. 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.

    Time frame: Baseline (Part 1) and Weeks 156 and 204

  17. 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.

    Time frame: Baseline (Part 1) and Weeks 156, 204

  18. 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.

    Time frame: Baseline (Part 1) and Weeks 156 and 204

  19. 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.

    Time frame: Baseline (Part 1) and Weeks 156, 204

  20. 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).

    Time frame: Baseline (Part 1) and every 4 weeks from Week 108 to Week 204

  21. 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).

    Time frame: Baseline (Part 1) and every 4 weeks from Week 108 to Week 204

  22. 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.

    Time frame: Part 2 Baseline (Week 108) and Weeks 156 and 204

  23. 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.

    Time frame: Part 2 Baseline (Week 108) and Weeks 156 and 204

  24. Part 2: Percentage Change From Week 24 (Part 1) in Whole Brain Volume

    Whole brain volume as measured by MRI.

    Time frame: Week 24 (Part 1) and Weeks 156 and 204

  25. Part 2: Percentage Change From Baseline (Part 1) in Whole Gray Matter Brain Volume

    Whole grey matter brain volume as measured by MRI.

    Time frame: Baseline (Part 1) and Weeks 156 and 204

  26. Part 2: Summary of New/Enlarging T2 Lesion Counts

    New or enlarging T2 lesions as measured by MRI.

    Time frame: Baseline (Part 1) up to Week 204

  27. Part 2: Percentage Change From Baseline (Part 1) in Number of New/Enlarging T2 Lesions

    New or enlarging T2 lesions as measured by MRI.

    Time frame: Baseline (Part 1) and Weeks 156 and 204

07

Results

Posted Jun 27, 2017

Participant flow

Part 1
Participant flow — Part 1
MilestonePlaceboNatalizumab 300 mg
Started449440
Withdrew prior to dosing01
Completed312326
Not completed137114
Withdrew: Other1024
Withdrew: Death01
Withdrew: Investigator decision76
Withdrew: Withdrawal by subject7448
Withdrew: Lack of efficacy168
Withdrew: Lost to follow-up11
Withdrew: Adverse event1518
Withdrew: Ongoing in follow-up148
Part 2
Participant flow — Part 2
MilestonePlaceboNatalizumab 300 mg
Started274292
Completed treatment for 48 weeks98111
Completed treatment for 96 weeks10
Completed treatment for > 96 weeks10
Completed36
Not completed271286
Withdrew: Adverse event114
Withdrew: Other234267
Withdrew: Investigator decision67
Withdrew: Withdrawal by subject145
Withdrew: Lack of efficacy41
Withdrew: Lost to follow-up22

Outcome measures

PrimaryPart 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.

Time frame:
Up to 96 weeks (2 years)
Reported as:
Number · percentage of participants
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)
percentage of participantsPlaceboNatalizumab 300 mg
Confirmed on ≥1 of EDSS, T25FW, or 9HPT at 2 years48 (43.1 to 52.4)44 (39.8 to 49.1)
Confirmed on EDSS at 2 years15 (11.7 to 18.3)16 (12.3 to 19.1)
Confirmed on T25FW at 2 years35 (30.8 to 39.7)35 (30.4 to 39.3)
Confirmed on 9HPT (either hand) at 2 years23 (19.3 to 27.1)15 (11.3 to 17.9)
Confirmed on 9HPT (dominant hand) at 2 years13 (10.2 to 16.5)10 (7.2 to 12.8)
Confirmed on 9HPT (non-dominant hand) at 2 years16 (12.5 to 19.2)10 (7.2 to 12.8)
Statistical analysis
  • Placebo vs Natalizumab 300 mg · Regression, Logistic · p = 0.2866 · Odds ratio (or): 0.86 · 95% CI 0.66 to 1.13active/placebo
  • Placebo vs Natalizumab 300 mg · Regression, Logistic · p = 0.7530 · Odds ratio (or): 1.06 · 95% CI 0.74 to 1.53active/placebo
  • Placebo vs Natalizumab 300 mg · Regression, Logistic · p = 0.9137 · Odds ratio (or): 0.98 · 95% CI 0.74 to 1.30active/placebo
  • Placebo vs Natalizumab 300 mg · Regression, Logistic · p = 0.0012 · Odds ratio (or): 0.56 · 95% CI 0.40 to 0.80Based on logistic regression, adjusted for Baseline EDSS (\<=5.5 or \>=6) and/or T25FW and/or 9HPT (either hand).
  • Placebo vs Natalizumab 300 mg · Regression, Logistic · p = 0.1251 · Odds ratio (or): 0.72 · 95% CI 0.48 to 1.09Based on logistic regression, adjusted for Baseline EDSS (\<=5.5 or \>=6) and/or T25FW and/or 9HPT (either hand).
  • Placebo vs Natalizumab 300 mg · Regression, Logistic · p = 0.0091 · Odds ratio (or): 0.58 · 95% CI 0.39 to 0.87Based on logistic regression, adjusted for Baseline EDSS (\<=5.5 or \>=6) and/or T25FW and/or 9HPT (either hand).
PrimaryNumber 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.

Time frame:
218 weeks
Reported as:
Number · participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
participantsPlaceboNatalizumab 300 mg
Any event250245
Moderate or severe event157158
Severe event2827
Related event6356
Serious event2439
Discontinuation of treatment due to event125
Withdrawal from study due to an event113
SecondaryPart 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.

Time frame:
Up to 96 weeks
Reported as:
Number · percentage of participants
Part 1: Percentage of Participants With a T25FW Response
percentage of participantsPlaceboNatalizumab 300 mg
Part 1: Percentage of Participants With a T25FW Response17 (12.7 to 20.3)19 (14.6 to 22.4)
Statistical analysis
  • Placebo vs Natalizumab 300 mg · Regression, Logistic · p = 0.4369 · Odds ratio (or): 1.16 · 95% CI 0.80 to 1.70active/placebo
SecondaryPart 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.

Time frame:
Baseline and Week 96
Reported as:
Mean · units on a scale
Part 1: Change From Baseline in the 12-Item MS Walking Scale (MSWS-12)
units on a scalePlaceboNatalizumab 300 mg
Part 1: Change From Baseline in the 12-Item MS Walking Scale (MSWS-12)4.04 ± 21.0612.70 ± 22.110
Statistical analysis
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.5409p-value for comparison between the active and placebo groups at Week 96 is based on ANCOVA model, adjusted for BL EDSS (\<=5.5 or \>=6) and BL MSWS-12.
SecondaryPart 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.

Time frame:
Baseline and Week 96
Reported as:
Mean · units on a scale
Part 1: Change From Baseline in Manual Ability Score Based on the ABILHAND Questionnaire
units on a scalePlaceboNatalizumab 300 mg
Part 1: Change From Baseline in Manual Ability Score Based on the ABILHAND Questionnaire-3.45 ± 14.739-2.44 ± 13.023
Statistical analysis
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.2586p-value for comparison between active and placebo groups at Week 96 is based on ANCOVA model, adjusted for BL EDSS (\<=5.5 or \>=6) and BL ABILHAND.
SecondaryPart 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.

Time frame:
Baseline and Week 96
Reported as:
Mean · units on a scale
Part 1: Change From Baseline in the Multiple Sclerosis Impact Scale-29 Physical (MSIS-29 Physical) Score
units on a scalePlaceboNatalizumab 300 mg
Part 1: Change From Baseline in the Multiple Sclerosis Impact Scale-29 Physical (MSIS-29 Physical) Score3.34 ± 20.9470.61 ± 19.885
Statistical analysis
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.1529p-value for comparison between active \& placebo groups at Wk 96 based on ANCOVA model, adjusted for BL EDSS (≤5.5 or ≥6) \& BL MSIS-29 physical score.
SecondaryPart 1: Percentage Change From Week 24 in Whole Brain Volume at Week 96

Whole brain volume as measured by MRI.

Time frame:
Week 24 and Week 96
Reported as:
Mean · percentage change
Part 1: Percentage Change From Week 24 in Whole Brain Volume at Week 96
percentage changePlaceboNatalizumab 300 mg
Part 1: Percentage Change From Week 24 in Whole Brain Volume at Week 96-0.72 ± 0.656-0.66 ± 0.596
Statistical analysis
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.2424 (natalizumab participants had a baseline after 6 months of treatment and the placebo-to-natalizumab group had a baseline of initiation of treatment)p-value for comparison between active and placebo groups at Week 96 is based on ANCOVA model, adjusted for BL EDSS (\<=5.5 or \>=6) and BL brain volume.
SecondaryPart 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.

Time frame:
Up to 96 weeks
Reported as:
Number · percentage of participants
Part 1: Percentage of Participants Defined as Confirmed Progressors on EDSS Functional System Scores
percentage of participantsPlaceboNatalizumab 300 mg
Part 1: Percentage of Participants Defined as Confirmed Progressors on EDSS Functional System Scores29 (25.2 to 33.7)25 (20.6 to 28.6)
Statistical analysis
  • Placebo vs Natalizumab 300 mg · Regression, Logistic · p = 0.1052 · Odds ratio (or): 0.78 · 95% CI 0.58 to 1.05Based on logistic regression, adjusted for baseline EDSS (\<=5.5 or \>=6).
SecondaryPart 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.

Time frame:
Week 156
Reported as:
Number · percentage of participants
Part 2: Percentage of Participants With Disability Worsening at 156 Weeks
percentage of participantsPlaceboNatalizumab 300 mg
Confirmed on ≥1 of EDSS, T25FW, 9HPT at 156 weeks61 (55.2 to 66.7)52 (45.8 to 57.3)
Confirmed on EDSS at 156 weeks23 (18.3 to 28.4)18 (13.8 to 22.6)
Confirmed on T25FW at 156 weeks46 (40.1 to 51.9)41 (35.2 to 46.5)
Confirmed on 9HPT (either hand) at 156 weeks28 (23.1 to 33.8)19 (14.4 to 23.4)
Confirmed on 9HPT (dominant hand) at 156 weeks18 (13.0 to 22.0)12 (8.0 to 15.4)
Confirmed on 9HPT (non-dominant hand) at 156 weeks18 (13.0 to 22.0)13 (9.2 to 16.9)
Statistical analysis
  • Placebo vs Natalizumab 300 mg · Regression, Logistic · p = 0.0205 · Odds ratio (or): 0.67 · 95% CI 0.47 to 0.94active/placebo
  • Placebo vs Natalizumab 300 mg · Regression, Logistic · p = 0.1305 · Odds ratio (or): 0.73 · 95% CI 0.48 to 1.10active/placebo
  • Placebo vs Natalizumab 300 mg · Regression, Logistic · p = 0.1988 · Odds ratio (or): 0.80 · 95% CI 0.57 to 1.12active/placebo
  • Placebo vs Natalizumab 300 mg · Regression, Logistic · p = 0.0093 · Odds ratio (or): 0.59 · 95% CI 0.39 to 0.88active/placebo
  • Placebo vs Natalizumab 300 mg · Regression, Logistic · p = 0.0540 · Odds ratio (or): 0.63 · 95% CI 0.39 to 1.01active/placebo
  • Placebo vs Natalizumab 300 mg · Regression, Logistic · p = 0.1410 · Odds ratio (or): 0.70 · 95% CI 0.44 to 1.12active/placebo
SecondaryPart 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.

Time frame:
Baseline (Part 1) and Weeks 156, 204
Reported as:
Mean · seconds
Part 2: Absolute Change From Baseline (Part 1) in T25FW
secondsPlaceboNatalizumab 300 mg
Overall: Change from BL to Week 156; n=255, 26412.80 ± 35.1117.78 ± 21.251
Overall: Change from BL to Week 204; n=39, 3825.01 ± 56.5829.01 ± 22.507
CP Group: Change from BL to Week 156; n=156, 13521.67 ± 42.51016.26 ± 26.943
CP Group: Change from BL to Week 204; n=25, 1840.06 ± 66.27520.89 ± 28.200
NP Group: Change from BL to Week 156; n=99, 129-1.17 ± 3.804-1.09 ± 3.593
NP Group: Change from BL to Week 204; n=14, 20-1.88 ± 5.917-1.67 ± 4.613
Statistical analysis
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.0273p-value for comparison between active and placebo at Week 156 based on ANCOVA model, adjusted for BL EDSS (\<=5.5 or\>=6) and BL T25FW.
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.1974p-value for comparison between active and placebo at Week 156 based on ANCOVA model, adjusted for BL EDSS (\<=5.5 or\>=6) and BL T25FW.
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.2506p-value for comparison between active and placebo at Week 156 based on ANCOVA model, adjusted for BL EDSS (\<=5.5 or\>=6) and BL T25FW.
SecondaryPart 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.

Time frame:
Baseline (Part 1) and Weeks 156, 204
Reported as:
Mean · percentage change
Part 2: Percentage Change From Baseline (Part 1) in T25FW
percentage changePlaceboNatalizumab 300 mg
Overall: Change from BL at Week 156; n=255, 26475.52 ± 166.19155.91 ± 130.286
Overall: Change from BL at Week 204; n=39, 38130.72 ± 272.11771.09 ± 177.668
CP Group: Change from BL at Week 156; n=156, 135127.05 ± 195.138113.51 ± 160.857
CP Group: Change from BL at Week 204; n=25, 18206.78 ± 316.344158.91 ± 228.458
NP Group: Change from BL at Week 156; n=99, 129-5.68 ± 21.708-4.37 ± 25.050
NP Group: Change from BL at Week 204; n=14, 20-5.09 ± 26.591-7.94 ± 29.856
Statistical analysis
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.0960p-value for comparison between active and placebo at Week 156 based on ANCOVA model, adjusted for BL EDSS (\<=5.5 or\>=6) and BL T25FW.
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.4957p-value for comparison between active and placebo at Week 156 based on ANCOVA model, adjusted for BL EDSS (\<=5.5 or\>=6) and BL T25FW.
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.2916p-value for comparison between active and placebo at Week 156 based on ANCOVA model, adjusted for BL EDSS (\<=5.5 or\>=6) and BL T25FW.
SecondaryPart 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.

Time frame:
Baseline (Part 1) and Weeks 156, 204
Reported as:
Mean · seconds
Part 2: Absolute Change From Baseline (Part 1) in 9HPT (Dominant Hand)
secondsPlaceboNatalizumab 300 mg
Overall: Change from BL to Week 156; n= 257, 2715.22 ± 27.7282.12 ± 16.719
Overall: Change from BL to Week 204; n=39, 380.56 ± 7.9232.65 ± 16.001
CP Group: Change from BL to Week 156; n=158, 13810.12 ± 33.6755.01 ± 20.625
CP Group: Change from BL to Week 204; n=24, 192.36 ± 9.1876.03 ± 21.994
NP Group: Change from BL to Week 156; n=99, 133-2.60 ± 9.543-0.89 ± 10.602
NP Group: Change from BL to Week 204; n=15, 19-2.32 ± 4.153-0.73 ± 4.292
Statistical analysis
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.1119p-value for comparison between active \& placebo groups at Week 156 based on ANCOVA model, adjusted for BL EDSS (≤5.5 or ≥6) \& BL 9HPT (dominant hand).
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.1129p-value for comparison between active \& placebo groups at Week 156 based on ANCOVA model, adjusted for BL EDSS (≤5.5 or ≥6) \& BL 9HPT (dominant hand).
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.2351p-value for comparison between active \& placebo groups at Week 156 based on ANCOVA model, adjusted for BL EDSS (≤5.5 or ≥6) \& BL 9HPT (dominant hand).
SecondaryPart 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.

Time frame:
Baseline (Part 1) and Weeks 156, 204
Reported as:
Mean · percentage change
Part 2: Percentage Change From Baseline (Part 1) in 9HPT (Dominant Hand)
percentage changePlaceboNatalizumab 300 mg
Overall: Change from BL to Week 156; n=257, 27114.32 ± 59.7275.25 ± 32.649
Overall: Change from BL to Week 204; n=39, 382.27 ± 19.1936.87 ± 32.333
CP Group: Change from BL to Week 156; n=158, 13825.87 ± 72.62112.84 ± 40.232
CP Group: Change from BL to Week 204; n=24, 198.43 ± 20.24716.25 ± 41.317
NP Group: Change from BL to Week 156; n=99, 133-4.10 ± 17.661-2.63 ± 19.436
NP Group: Change from BL to Week 204; n=15, 19-7.57 ± 12.560-2.52 ± 15.998
Statistical analysis
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.0261p-value for comparison between active \& placebo groups at Week 156 based on ANCOVA model, adjusted for BL EDSS (≤5.5 or ≥6) \& BL 9HPT (dominant hand).
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.0585p-value for comparison between active \& placebo groups at Week 156 based on ANCOVA model, adjusted for BL EDSS (≤5.5 or ≥6) \& BL 9HPT (dominant hand).
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.6095p-value for comparison between active \& placebo groups at Week 156 based on ANCOVA model, adjusted for BL EDSS (≤5.5 or ≥6) \& BL 9HPT (dominant hand).
SecondaryPart 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.

Time frame:
Baseline (Part 1) and Weeks 156, 204
Reported as:
Mean · seconds
Part 2: Absolute Change From Baseline (Part 1) in 9HPT (Non-Dominant Hand)
secondsPlaceboNatalizumab 300 mg
Overall: Change from BL to Week 156; n=254, 2695.24 ± 32.9104.62 ± 30.333
Overall: Change from BL to Week 204; n=40, 401.41 ± 16.9524.91 ± 33.808
CP Group: Change from BL to Week 156; n=155, 13711.25 ± 39.51311.25 ± 38.296
CP Group: Change from BL to Week 204; n=25, 205.87 ± 17.47417.20 ± 34.632
NP Group: Change from BL to Week 156; n=99, 132-4.17 ± 13.999-2.26 ± 16.311
NP Group: Change from BL to Week 204; n=15, 20-6.04 ± 13.491-7.39 ± 28.780
Statistical analysis
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.7230p-value for comparison between active \& placebo groups at Week 156 based on ANCOVA, adjusted for BL EDSS (≤5.5 or ≥6) \& BL 9HPT (non-dominant hand).
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.8781p-value for comparison between active \& placebo groups at Week 156 based on ANCOVA, adjusted for BL EDSS (≤5.5 or ≥6) \& BL 9HPT (non-dominant hand).
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.2751p-value for comparison between active \& placebo groups at Week 156 based on ANCOVA, adjusted for BL EDSS (≤5.5 or ≥6) \& BL 9HPT (non-dominant hand).
SecondaryPart 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.

Time frame:
Baseline (Part 1) and Weeks 156, 204
Reported as:
Mean · percentage change
Part 2: Percentage Change From Baseline (Part 1) in 9HPT (Non-Dominant Hand)
percentage changePlaceboNatalizumab 300 mg
Overall: Change from BL to Week 156; n=254, 26913.87 ± 64.95911.04 ± 47.942
Overall: Change from BL to Week 204; n=40, 403.67 ± 28.75518.57 ± 62.537
CP Group: Change from BL to Week 156; n=155, 13726.33 ± 79.95723.51 ± 60.074
CP Group: Change from BL to Week 204; n=25, 2011.87 ± 31.05043.12 ± 80.639
NP Group: Change from BL to Week 156; n=99, 132-5.63 ± 14.765-1.89 ± 24.987
NP Group: Change from BL to Week 204; n=15, 20-9.98 ± 18.188-5.98 ± 16.005
Statistical analysis
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.5051p-value for comparison between active \& placebo groups at Week 156 based on ANCOVA, adjusted for BL EDSS (≤5.5 or ≥6) \& BL 9HPT (non-dominant hand).
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.7283p-value for comparison between active \& placebo groups at Week 156 based on ANCOVA, adjusted for BL EDSS (≤5.5 or ≥6) \& BL 9HPT (non-dominant hand).
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.1666p-value for comparison between active \& placebo groups at Week 156 based on ANCOVA, adjusted for BL EDSS (≤5.5 or ≥6) \& BL 9HPT (non-dominant hand).
SecondaryPart 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.

Time frame:
Baseline (Part 1) and Weeks 156, 204
Reported as:
Mean · units on a scale
Part 2: Absolute Change From Baseline (Part 1) in EDSS
units on a scalePlaceboNatalizumab 300 mg
Overall: Change from BL to Week 156; n=260, 2750.11 ± 0.7460.06 ± 0.797
Overall: Change from BL to Week 204; n=40, 40-0.01 ± 0.8950.15 ± 0.928
CP Group: Change from BL to Week 156; n=162, 1410.38 ± 0.6310.36 ± 0.703
CP Group: Change from BL to Week 204; n=25, 200.28 ± 0.5420.68 ± 0.634
NP Group: Change from BL to Week 156; n=98, 134-0.33 ± 0.718-0.25 ± 0.775
NP Group: Change from BL to Week 204; n=15, 20-0.50 ± 1.150-0.38 ± 0.887
Statistical analysis
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.4330p-value for comparison between active \& placebo groups at Week 156 based on ANCOVA, adjusted for BL EDSS (≤5.5 or ≥6).
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.7122p-value for comparison between active \& placebo groups at Week 156 based on ANCOVA, adjusted for BL EDSS (≤5.5 or ≥6).
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.3861p-value for comparison between active \& placebo groups at Week 156 based on ANCOVA, adjusted for BL EDSS (≤5.5 or ≥6).
SecondaryPart 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.

Time frame:
Baseline (Part 1) and Weeks 156, 204
Reported as:
Mean · percentage change
Part 2: Percentage Change From Baseline (Part 1) in EDSS
percentage changePlaceboNatalizumab 300 mg
Overall: Change from BL to Week 156; n=260, 2752.07 ± 15.1881.65 ± 16.530
Overall: Change from BL to Week 204; n=40, 40-0.63 ± 17.8892.91 ± 18.656
CP Group Change from BL to Week 156; n=162, 1417.23 ± 13.5137.30 ± 15.728
CP Group Change from BL to Week 204; n=25, 205.31 ± 10.71113.18 ± 13.957
NP Group Change from BL to Week 156; n=98, 134-6.47 ± 13.951-4.29 ± 15.266
NP Group Change from BL to Week 204; n=15, 20-10.53 ± 22.953-7.35 ± 17.260
Statistical analysis
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.7225p-value for comparison between active \& placebo groups at Week 156 based on ANCOVA, adjusted for BL EDSS (≤5.5 or ≥6).
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.9121p-value for comparison between active \& placebo groups at Week 156 based on ANCOVA, adjusted for BL EDSS (≤5.5 or ≥6).
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.2594p-value for comparison between active \& placebo groups at Week 156 based on ANCOVA, adjusted for BL EDSS (≤5.5 or ≥6).
SecondaryPart 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.

Time frame:
Baseline (Part 1) and Weeks 156 and 204
Reported as:
Mean · meters
Part 2: Absolute Change From Baseline (Part 1) in the 6-Minute Walk Test (6MWT)
metersPlaceboNatalizumab 300 mg
Change from BL to Week 156; n=272, 289-32.1 ± 117.55-40.4 ± 219.60
Change from BL to Week 204; n=272, 290-33.3 ± 119.40-40.7 ± 219.58
Statistical analysis
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.8066p-value for comparison between active \& placebo groups at Week 156 based on ANCOVA model, adjusted for BL EDSS (≤5.5 or ≥6) \& BL 6MWT.
SecondaryPart 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.

Time frame:
Baseline (Part 1) and Weeks 156, 204

No measurements were reported for this outcome.

SecondaryPart 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.

Time frame:
Baseline (Part 1) and Weeks 156 and 204
Reported as:
Mean · units on a scale
Part 2: Absolute Change From Baseline (Part 1) in the MSIS-29 Physical Score
units on a scalePlaceboNatalizumab 300 mg
Change from BL to Week 1560.32 ± 20.9430.05 ± 20.843
Change to from BL Week 2040.91 ± 21.018-0.28 ± 20.596
Statistical analysis
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.7084p-value for comparison between active \& placebo at Week 156 based on ANCOVA model, adjusted for BL EDSS (≤5.5 or ≥6) \& BL MSIS-29 physical score.
SecondaryPart 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.

Time frame:
Baseline (Part 1) and Weeks 156, 204

No measurements were reported for this outcome.

SecondaryPart 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).

Time frame:
Baseline (Part 1) and every 4 weeks from Week 108 to Week 204
Reported as:
Mean · units on a scale
Part 2: Absolute Change From Baseline (Part 1) in the Symbol Digit Modalities Test (SDMT)
units on a scalePlaceboNatalizumab 300 mg
Change from BL to Week 10813.6 ± 14.1915.5 ± 13.82
Change from BL to Week 11214.4 ± 13.7215.1 ± 13.50
Change from BL to Week 11614.1 ± 13.8415.3 ± 13.51
Change from BL to Week 12014.3 ± 14.2315.3 ± 13.68
Change from BL to Week 12414.4 ± 14.0215.7 ± 13.69
Change from BL to Week 12815.1 ± 14.4915.7 ± 13.72
Change from BL to Week 13215.1 ± 14.5215.6 ± 13.63
Change from BL to Week 13614.8 ± 14.5616.3 ± 13.75
Change from BL to Week 14015.4 ± 14.9816.4 ± 14.29
Change from BL to Week 14415.7 ± 15.2316.2 ± 14.22
Change from BL to Week 14815.5 ± 15.3416.3 ± 14.35
Change from BL to Week 15215.5 ± 14.9816.3 ± 14.25
Change from BL to Week 15611.2 ± 13.1012.3 ± 14.59
Change from BL to Week 16015.2 ± 14.9216.2 ± 14.61
Change from BL to Week 16415.6 ± 15.2116.3 ± 14.64
Change from BL to Week 16815.8 ± 15.5216.4 ± 14.78
Change from BL to Week 17215.6 ± 15.4016.3 ± 14.64
Change from BL to Week 17615.5 ± 15.5816.3 ± 14.91
Change from BL to Week 18015.5 ± 15.2316.4 ± 14.89
Change from BL to Week 18415.6 ± 15.3416.3 ± 14.81
Change from BL to Week 18815.6 ± 15.3816.4 ± 14.77
Change from BL to Week 19215.6 ± 15.4616.3 ± 14.79
Change from BL to Week 19615.7 ± 15.4516.3 ± 14.69
Change from BL to Week 20015.7 ± 15.4716.3 ± 14.69
Change from BL to Week 20415.7 ± 15.4316.3 ± 14.69
Statistical analysis
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.3465p-value for comparison between active and placebo at Week 156 based on ANCOVA model, adjusted for BL EDSS (\<=5.5 or\>=6) and BL SDMT.
SecondaryPart 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).

Time frame:
Baseline (Part 1) and every 4 weeks from Week 108 to Week 204

No measurements were reported for this outcome.

SecondaryPart 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.

Time frame:
Part 2 Baseline (Week 108) and Weeks 156 and 204
Reported as:
Mean · percentage of impairment
Part 2: Absolute Change From Baseline (Part 2) in the Work Productivity and Activity Impairment - Multiple Sclerosis (WPAI-MS) Questionnaire
percentage of impairmentPlaceboNatalizumab 300 mg
Absenteeism: Week 1082.6 ± 12.801.4 ± 8.24
Absenteeism: Week 1563.0 ± 14.614.1 ± 17.36
Absenteeism: Week 2043.0 ± 14.614.2 ± 16.89
Presenteeism: Week 10830.6 ± 12.1030.9 ± 11.71
Presenteeism: Week 15630.8 ± 12.1733.0 ± 14.23
Presenteeism: Week 20431.0 ± 12.2932.2 ± 13.78
Work Productivity Loss: Week 10830.9 ± 12.3631.2 ± 11.70
Work Productivity Loss: Week 15631.6 ± 13.5433.9 ± 15.75
Work Productivity Loss: Week 20431.9 ± 13.6633.3 ± 15.61
Activity Impairment: Week 10856.1 ± 24.7858.0 ± 24.84
Activity Impairment: Week 15656.8 ± 26.4958.5 ± 24.08
Activity Impairment: Week 20457.2 ± 25.1559.8 ± 23.60
SecondaryPart 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.

Time frame:
Part 2 Baseline (Week 108) and Weeks 156 and 204
Reported as:
Mean · percentage change
Part 2: Percentage Change From Baseline (Part 2) in the WPAI-MS Questionnaire
percentage changePlaceboNatalizumab 300 mg
Absenteeism: Change at Week 156; n=18,17-10.3 ± 116.81-7.4 ± 95.77
Absenteeism: Change at Week 204; n=18, 17-6.6 ± 116.90151.5 ± 457.29
Presenteeism: Change at Week 156; n=264, 2854.0 ± 50.0814.4 ± 90.39
Presenteeism: Change at Week 204; n=264, 2855.3 ± 51.237.4 ± 58.95
WPL: Change at Week 156; n=264,2864.7 ± 51.7316.8 ± 95.43
WPL: Change at Week 204; n=264, 2865.9 ± 53.4410.6 ± 69.34
AI: Change at Week 156; n=264, 28416.0 ± 95.6815.7 ± 83.70
AI: Change at Week 204; n=264, 28416.1 ± 88.5620.4 ± 99.54
SecondaryPart 2: Percentage Change From Week 24 (Part 1) in Whole Brain Volume

Whole brain volume as measured by MRI.

Time frame:
Week 24 (Part 1) and Weeks 156 and 204
Reported as:
Mean · percentage change
Part 2: Percentage Change From Week 24 (Part 1) in Whole Brain Volume
percentage changePlaceboNatalizumab 300 mg
Change from Week 24 to Week 156; n=155, 175-1.164 ± 0.8228-0.948 ± 0.7193
Change from Week 24 to Week 204; n=28, 24-1.687 ± 1.2872-1.517 ± 0.8412
Statistical analysis
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.0070 (natalizumab participants had a baseline after 6 months of treatment and the placebo-to-natalizumab group had a baseline of initiation of treatment)p-value for comparison between active \& placebo at Week 156 based on ANCOVA model, adjusted for BL EDSS (≤5.5 or ≥6) \& BL normalized brain volume.
SecondaryPart 2: Percentage Change From Baseline (Part 1) in Whole Gray Matter Brain Volume

Whole grey matter brain volume as measured by MRI.

Time frame:
Baseline (Part 1) and Weeks 156 and 204
Reported as:
Mean · percentage change
Part 2: Percentage Change From Baseline (Part 1) in Whole Gray Matter Brain Volume
percentage changePlaceboNatalizumab 300 mg
Change from Baseline to Week 156; n=149, 170-1.566 ± 0.9303-1.514 ± 0.8969
Change from Baseline to Week 204; n=26, 20-1.883 ± 1.4222-2.086 ± 0.9068
Statistical analysis
  • Placebo vs Natalizumab 300 mg · ANCOVA · p = 0.5034 (natalizumab participants had a baseline after 6 months of treatment and the placebo-to-natalizumab group had a baseline of initiation of treatment)p-value for comparison between active \& placebo at Week 156 based on ANCOVA model, adjusted for BL EDSS (≤5.5 or ≥6) \& BL WGM brain volume
SecondaryPart 2: Summary of New/Enlarging T2 Lesion Counts

New or enlarging T2 lesions as measured by MRI.

Time frame:
Baseline (Part 1) up to Week 204
Reported as:
Mean · lesions
Part 2: Summary of New/Enlarging T2 Lesion Counts
lesionsPlaceboNatalizumab 300 mg
At Week 24 compared to BL; n=272, 2872.1 ± 4.240.6 ± 3.27
At Week 48 compared to Week 24; n=272, 2891.8 ± 4.470.0 ± 0.37
At Week 72 compared to Week 48; n=271, 2871.6 ± 3.760.0 ± 0.19
At Week 96 compared to Week 72; n=269, 2841.8 ± 4.330.0 ± 0.00
At Week 108 compared to Week 96; n=269, 2881.2 ± 3.380.0 ± 0.13
At Week 156 compared to Week 108; n=245, 2580.2 ± 0.790.0 ± 0.20
At Week 204 compared to Week 156; n=50, 470.0 ± 0.200.0 ± 0.15
Cumulative count from BL to Week 204; n=274, 2918.6 ± 16.040.7 ± 3.53
Statistical analysis
  • Placebo vs Natalizumab 300 mg · negative binomial regression model · p = < 0.0001 (p-value for comparison between the active and placebo groups at Week 156 compared to Week 108 is based on negative binomial regression model, adjusted for baseline EDSS (\<=5.5 or \>=6) and baseline volume of T2 lesions.)natalizumab participants had a baseline after 6 months of treatment and the placebo-to-natalizumab group had a baseline of initiation of treatment
SecondaryPart 2: Percentage Change From Baseline (Part 1) in Number of New/Enlarging T2 Lesions

New or enlarging T2 lesions as measured by MRI.

Time frame:
Baseline (Part 1) and Weeks 156 and 204

No measurements were reported for this outcome.

Adverse events

Collected over Adverse events are captured through the last study visit; participants were followed through Week 228, or 24 weeks following last dose of study treatment, or premature withdrawal.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo—100/449 (22.3%)347/449 (77.3%)
Natalizumab 300 mg—90/439 (20.5%)325/439 (74%)
Most frequent serious events
Showing 10 of 150
Most frequent serious events
EventPlaceboNatalizumab 300 mg
Multiple sclerosis relapseNervous system disorders28/44921/439
Urinary tract infectionInfections and infestations12/4495/439
FallInjury, poisoning and procedural complications3/4496/439
PneumoniaInfections and infestations5/4492/439
Multiple sclerosisNervous system disorders5/4490/439
Anaphylactic reactionImmune system disorders0/4493/439
CellulitisInfections and infestations2/4493/439
GastroenteritisInfections and infestations0/4493/439
UrosepsisInfections and infestations1/4493/439
Uhthoff's phenomenonNervous system disorders3/4491/439
Most frequent other events
Showing 10 of 22
Most frequent other events
EventPlaceboNatalizumab 300 mg
Multiple sclerosis relapseNervous system disorders116/44968/439
Urinary tract infectionInfections and infestations103/449100/439
NasopharyngitisInfections and infestations73/44998/439
FallInjury, poisoning and procedural complications85/44982/439
HeadacheNervous system disorders50/44966/439
FatigueGeneral disorders53/44959/439
Back painMusculoskeletal and connective tissue disorders50/44945/439
Upper respiratory tract infectionInfections and infestations30/44948/439
ArthralgiaMusculoskeletal and connective tissue disorders40/44943/439
Pain in extremityMusculoskeletal and connective tissue disorders42/44942/439

Baseline characteristics

Safety population: all participants who were randomized and received at least 1 infusion of study treatment in Part 1.

Age, Customized
Age, Customized(participants)PlaceboNatalizumab 300 mgTotal
20 - 29 years101020
30 - 39 years7350123
40 - 49 years162194356
≥ 50 years204185389
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboNatalizumab 300 mgTotal
Female280270550
Male169169338
08

Study locations

161 sites
  • Research Site
    Phoenix, Arizona 85013, United States
  • Research Site
    Tucson, Arizona 85741, United States
  • Research Site
    Fullerton, California 92835, United States
  • Research Site
    Los Angeles, California 90027, United States
  • Research Site
    Aurora, Colorado 80045, United States
  • Research Site
    Tampa, Florida 33612, United States
  • Research Site
    Chicago, Illinois 60637, United States
  • Research Site
    Lake Barrington, Illinois 60010, United States
  • Research Site
    Peoria, Illinois 61606, United States
  • Research Site
    Indianapolis, Indiana 46202, United States
  • Research Site
    Indianapolis, Indiana 46256, United States
  • Research Site
    Kansas City, Kansas 66160, United States
  • Research Site
    Lexington, Kentucky 40513, United States
  • Research Site
    Lexington, Kentucky 40536, United States
  • Research Site
    Baltimore, Maryland 21287, United States
  • Research Site
    Burlington, Massachusetts 01805, United States
  • Research Site
    Omaha, Nebraska 68198, United States
  • Research Site
    Lebanon, New Hampshire 03756, United States
  • Research Site
    Teaneck, New Jersey 07666, United States
  • Research Site
    Latham, New York 12110, United States
  • Research Site
    New York, New York 10029, United States
  • Research Site
    Advance, North Carolina 27006, United States
  • Research Site
    Charlotte, North Carolina 28207, United States
  • Research Site
    Raleigh, North Carolina 27607, United States
  • Research Site
    Akron, Ohio 44320, United States
  • Research Site
    Uniontown, Ohio 44685, United States
  • Research Site
    Oklahoma City, Oklahoma 73104, United States
  • Research Site
    Clackamas, Oregon 97015, United States
  • Research Site
    Portland, Oregon 97225, United States
  • Research Site
    Portland, Oregon 97239, United States
  • Research Site
    Nashville, Tennessee 37215, United States
  • Research Site
    Charlottesville, Virginia 22903, United States
  • Research Site
    Seattle, Washington 98101, United States
  • Research Site
    Green Bay, Wisconsin 54311, United States
  • Research Site
    Milwaukee, Wisconsin 53215, United States
  • Research Site
    La Louviere, 7100, Belgium
  • Research Site
    Melsbroek, 1820, Belgium
  • Research Site
    Overpelt, 3900, Belgium
  • Research Site
    Calgary, Alberta T2N 2T9, Canada
  • Research Site
    Edmonton, Alberta T6G 2G3, Canada
  • Research Site
    Vancouver, British Columbia V6T 1Z3, Canada
  • Research Site
    Halifax, Nova Scotia B3H 4K4, Canada
  • Research Site
    Kingston, Ontario K7L 2V7, Canada
  • Research Site
    London, Ontario N6A 5A5, Canada
  • Research Site
    Ottawa, Ontario K1H 8L6, Canada
  • Research Site
    Toronto, Ontario M4N 3M5, Canada
  • Research Site
    Gatineau, Quebec J9J 0A5, Canada
  • Research Site
    Greenfield Park, Quebec J4V 2J2, Canada
  • Research Site
    Montreal, Quebec H2L 4M1, Canada
  • Research Site
    Montreal, Quebec H3A 2B4, Canada
  • Research Site
    Hradec Kralove, Bohemia 50005, Czechia
  • Research Site
    Brno, 65691, Czechia
  • Research Site
    Olomouc, 77520, Czechia
  • Research Site
    Praha, 12111, Czechia
  • Research Site
    Arthus C, 8000, Denmark
  • Research Site
    Esbjerg, 6700, Denmark
  • Research Site
    Glostrup, 2600, Denmark
  • Research Site
    København Ø, 2100, Denmark
  • Research Site
    Odense, 5000, Denmark
  • Research Site
    Jyväskylä, 40620, Finland
  • Research Site
    Tampere, 33520, Finland
  • Research Site
    Turku, 20520, Finland
  • Research Site
    Nice, Alpes Maritimes 06002, France
  • Research Site
    Marseille cedex 5, Bouches-du-Rhône 13385, France
  • Research Site
    Nantes, Loire Atlantique 44093, France
  • Research Site
    Nancy, Meurthe et Moselle 54035, France
  • Research Site
    Lille Cedex, Nord 59000, France
  • Research Site
    Bron cedex, Rhone 69677, France
  • Research Site
    Salouel, Somme 80054, France
  • Research Site
    Bordeaux, 33076, France
  • Research Site
    Bad Wilbad, Baden Wuerttemberg 75323, Germany
  • Research Site
    Tuebingen, Baden Wuerttemberg 72076, Germany
  • Research Site
    Bad Mergentheim, Baden-Wuerttemberg 97980, Germany
  • Research Site
    Muenchen, Bayern 81377, Germany
  • Research Site
    Muenchen, Bayern 81675, Germany
  • Research Site
    Hennigsdorf, Brandenburg 16761, Germany
  • Research Site
    Teupitz, Brandenburg 15755, Germany
  • Research Site
    Kassel, Hessen 34121, Germany
  • Research Site
    Duesseldorf, Nordrhein Westfalen 40225, Germany
  • Research Site
    Muenster, Nordrhein Westfalen 48149, Germany
  • Research Site
    Dresden, Sachsen 01307, Germany
  • Research Site
    Dublin, D4, Ireland
  • Research Site
    Dublin, D9, Ireland
  • Research Site
    Jerusalem, 91120, Israel
  • Research Site
    Ramat Gan, 52621, Israel
  • Research Site
    Baggiovara, Modena 41100, Italy
  • Research Site
    Cefalu, Palermo 90015, Italy
  • Research Site
    Gallarate, Varese 21013, Italy
  • Research Site
    Bari, 70124, Italy
  • Research Site
    Florence, 50134, Italy
  • Research Site
    Genova, 16132, Italy
  • Research Site
    Milano, 20122, Italy
  • Research Site
    Milano, 20132, Italy
  • Research Site
    Naples, 80138, Italy
  • Research Site
    Napoli, 80131, Italy
  • Research Site
    Palermo, 90146, Italy
  • Research Site
    Pavia, 27100, Italy
  • Research Site
    Rome, 00176, Italy
  • Research Site
    Rome, 00189, Italy
  • Research Site
    Amsterdam, 1081 HV, Netherlands

Showing the first 100 of 161 sites across 17 countries.

09

References and documents

Publications

  • 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. PubMed 35720980 ↗
  • 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. PubMed 34376508 ↗
  • 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. PubMed 29545067 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 11, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01416181
Lead sponsor
Biogen
Responsible party
Sponsor
First posted
Aug 12, 2011
Start date
Sep 13, 2011
Primary completion
Jul 28, 2015
Completion
Apr 13, 2016
Results posted
Jun 27, 2017
Last update
Sep 11, 2017

Study contacts

Medical Director
study director · Biogen

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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