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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-021978-11 | EudraCT Number |
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The ASCEND Study did not achieve statistical significance on the primary or secondary endpoints.
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| natalizumab | Experimental | 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. |
|
| Placebo | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| natalizumab | Drug | Administered as specified in the treatment arm |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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):
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. | Up to 96 weeks (2 years) |
| 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. | 218 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Key Inclusion Criteria (Part 1):
Key Exclusion Criteria (Part 1):
Treatment History (Part 1)
Key Inclusion Criteria (Part 2):
Key Exclusion Criteria (Part 2):
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Biogen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Phoenix | Arizona | 85013 | United States | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37652990 | Derived | Loomis SJ, Sadhu N, Fisher E, Gafson AR, Huang Y, Yang C, Hughes EE, Marshall E, Herman A, John S, Runz H, Jia X, Bhangale T, Bronson PG. Genome-wide study of longitudinal brain imaging measures of multiple sclerosis progression across six clinical trials. Sci Rep. 2023 Aug 31;13(1):14313. doi: 10.1038/s41598-023-41099-0. | |
| 35720980 |
| Label | URL |
|---|---|
| Find out what to expect with TYSABRI MS treatment | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Part 1: participants were randomized to receive placebo intravenously (IV) every 4 weeks for 96 weeks. Part 2: participants transitioned to receive open-label natalizumab 300 mg IV every 4 weeks for at least 96 weeks. |
| FG001 | Natalizumab 300 mg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Part 1 |
|
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| Placebo | Drug | Matched placebo in part 1 |
|
| Up to 96 weeks |
| 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. | Baseline and Week 96 |
| 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. | Baseline and Week 96 |
| 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. | Baseline and Week 96 |
| Part 1: Percentage Change From Week 24 in Whole Brain Volume at Week 96 | Whole brain volume as measured by MRI. | Week 24 and Week 96 |
| 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:
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. | Up to 96 weeks |
| 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. | Week 156 |
| 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. | Baseline (Part 1) and Weeks 156, 204 |
| 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. | Baseline (Part 1) and Weeks 156, 204 |
| 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. | Baseline (Part 1) and Weeks 156, 204 |
| 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. | Baseline (Part 1) and Weeks 156, 204 |
| 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. | Baseline (Part 1) and Weeks 156, 204 |
| 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. | Baseline (Part 1) and Weeks 156, 204 |
| 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. | Baseline (Part 1) and Weeks 156, 204 |
| 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. | Baseline (Part 1) and Weeks 156, 204 |
| 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. | Baseline (Part 1) and Weeks 156 and 204 |
| 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. | Baseline (Part 1) and Weeks 156, 204 |
| 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. | Baseline (Part 1) and Weeks 156 and 204 |
| 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. | Baseline (Part 1) and Weeks 156, 204 |
| 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). | Baseline (Part 1) and every 4 weeks from Week 108 to Week 204 |
| 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). | Baseline (Part 1) and every 4 weeks from Week 108 to Week 204 |
| 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 Baseline (Week 108) and Weeks 156 and 204 |
| 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 Baseline (Week 108) and Weeks 156 and 204 |
| Part 2: Percentage Change From Week 24 (Part 1) in Whole Brain Volume | Whole brain volume as measured by MRI. | Week 24 (Part 1) and Weeks 156 and 204 |
| Part 2: Percentage Change From Baseline (Part 1) in Whole Gray Matter Brain Volume | Whole grey matter brain volume as measured by MRI. | Baseline (Part 1) and Weeks 156 and 204 |
| Part 2: Summary of New/Enlarging T2 Lesion Counts | New or enlarging T2 lesions as measured by MRI. | Baseline (Part 1) up to Week 204 |
| Part 2: Percentage Change From Baseline (Part 1) in Number of New/Enlarging T2 Lesions | New or enlarging T2 lesions as measured by MRI. | Baseline (Part 1) and Weeks 156 and 204 |
| 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 |
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| 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 Louvière | 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 Králové | Bohemia | 50005 | Czechia |
| Research Site | Brno | 65691 | Czechia |
| Research Site | Olomouc | 77520 | Czechia |
| Research Site | Prague | 12111 | Czechia |
| Research Site | Arthus C | 8000 | Denmark |
| Research Site | Esbjerg | 6700 | Denmark |
| Research Site | Glostrup Municipality | 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 | Bouches-du-Rhône | 13385 | France |
| Research Site | Nantes | Loire Atlantique | 44093 | France |
| Research Site | Nancy | Meurthe et Moselle | 54035 | France |
| Research Site | Lille | Nord | 59000 | France |
| Research Site | Bron | Rhone | 69677 | France |
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| Research Site | Bordeaux | 33076 | France |
| Research Site | Bad Mergentheim | Baden-Wurttemberg | 97980 | Germany |
| Research Site | Bad Wilbad | Baden-Wurttemberg | 75323 | Germany |
| Research Site | Tübingen | Baden-Wurttemberg | 72076 | Germany |
| Research Site | Munich | Bavaria | 81377 | Germany |
| Research Site | Munich | Bavaria | 81675 | Germany |
| Research Site | Hennigsdorf | Brandenburg | 16761 | Germany |
| Research Site | Teupitz | Brandenburg | 15755 | Germany |
| Research Site | Kassel | Hesse | 34121 | Germany |
| Research Site | Düsseldorf | North Rhine-Westphalia | 40225 | Germany |
| Research Site | Münster | North Rhine-Westphalia | 48149 | Germany |
| Research Site | Dresden | Saxony | 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 | Cefalù | Palermo | 90015 | Italy |
| Research Site | Gallarate | Varese | 21013 | Italy |
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| Research Site | Naples | 80131 | Italy |
| Research Site | Naples | 80138 | Italy |
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| Research Site | Pavia | 27100 | Italy |
| Research Site | Rome | 00176 | Italy |
| Research Site | Rome | 00189 | Italy |
| Research Site | 's-Hertogenbosch | 5223 GZ | Netherlands |
| Research Site | Amsterdam | 1081 HV | Netherlands |
| Research Site | Breda | 4800 RK | Netherlands |
| Research Site | Hoorn | 1624 NP | Netherlands |
| Research Site | Nieuwegein | 3430 EM | Netherlands |
| Research Site | Sittard-Geleen | 6130 MB | Netherlands |
| Research Site | Bialystok | 15-276 | Poland |
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| Research Site | Belgorod | 308007 | Russia |
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| Research Site | Moscow | 127015 | Russia |
| Research Site | Saint Petersburg | 197110 | Russia |
| Research Site | Tyumen | 625000 | Russia |
| Research Site | Barcelona | 08035 | Spain |
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| Research Site | Barcelona | 08041 | Spain |
| Research Site | El Palmar | 30120 | Spain |
| Research Site | Madrid | 28034 | Spain |
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| Research Site | Seville | 41009 | Spain |
| Research Site | Gothenburg | 41345 | Sweden |
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| Research Site | Stockholm | 14186 | Sweden |
| Research Site | Stockholm | 17176 | Sweden |
| Research Site | Stockholm | 18288 | Sweden |
| Research Site | Umeå | 90185 | Sweden |
| Research Site | Irvine | Ayrshire | KA12 8SS | United Kingdom |
| Research Site | Edgbaston | Birmingham | B15 2TH | United Kingdom |
| Research Site | Exeter | Devon | EX2 5DW | United Kingdom |
| Research Site | Plymouth | Devon | PL6 8BX | United Kingdom |
| Research Site | London | Greater London | E1 2AT | United Kingdom |
| Research Site | London | Greater London | SE5 9RS | United Kingdom |
| Research Site | Hammersmith | London | W6 8RF | United Kingdom |
| Research Site | Edinburgh | Lothian Region | EH4 2XU | United Kingdom |
| Research Site | Salford | Manchester | M6 8HD | United Kingdom |
| Research Site | Liverpool | Merseyside | L9 7LJ | United Kingdom |
| Research Site | Norwich | Norfolk | NR4 7UY | United Kingdom |
| Research Site | Nottingham | Nottinghamshire | NG7 2UH | United Kingdom |
| Research Site | Morriston | Swansea | SA6 6NL | United Kingdom |
| Research Site | Newcastle | Tyne | NE1 4LP | United Kingdom |
| Research Site | Brighton | BN2 5BE | United Kingdom |
| Research Site | London | WC1N 3BG | United Kingdom |
| Research Site | Sheffield | S10 2JF | United Kingdom |
| 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. |
| 34376508 | Derived | 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. |
| 29545067 | Derived | 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. |
Part 1: participants were randomized to receive 300 mg of natalizumab IV every 4 weeks for 96 weeks. Part 2: participants transitioned to receive open-label natalizumab 300 mg IV every 4 weeks for at least 96 weeks. |
| Withdrew Prior to Dosing |
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| COMPLETED |
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| NOT COMPLETED |
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| Part 2 |
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Safety population: all participants who were randomized and received at least 1 infusion of study treatment in Part 1.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Part 1: participants were randomized to receive placebo IV every 4 weeks for 96 weeks. Part 2: participants transitioned to receive open-label natalizumab 300 mg IV every 4 weeks for at least 96 weeks. |
| BG001 | Natalizumab 300 mg | Part 1: participants were randomized to receive 300 mg of natalizumab IV every 4 weeks for 96 weeks. Part 2: participants transitioned to receive open-label natalizumab 300 mg IV every 4 weeks for at least 96 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||
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| Age, Customized | Number | participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | 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):
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. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 96 weeks (2 years) |
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| Primary | 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. | Safety population: all participants who were randomized in Part 1 and received at least 1 infusion of study treatment in Part 2. | Posted | Number | participants | 218 weeks |
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| Secondary | 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. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment. Excludes participants who withdrew prior to 1 year (defined as stopping treatment prior to Week 48) of participation in the study. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 96 weeks |
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| Secondary | 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. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment. Excludes participants who withdrew prior to 1 year (defined as stopping treatment prior to Week 48) of participation in the study. | Posted | Mean | Standard Deviation | units on a scale | Baseline and Week 96 |
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| Secondary | 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. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment. Excludes participants who withdrew prior to 1 year (defined as stopping treatment prior to Week 48) of participation in the study. | Posted | Mean | Standard Deviation | units on a scale | Baseline and Week 96 |
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| Secondary | 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. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment. Excludes participants who withdrew prior to 1 year (defined as stopping treatment prior to Week 48) of participation in the study. | Posted | Mean | Standard Deviation | units on a scale | Baseline and Week 96 |
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| Secondary | Part 1: Percentage Change From Week 24 in Whole Brain Volume at Week 96 | Whole brain volume as measured by MRI. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment. Includes those participants with an assessment at Weeks 24 and 96. | Posted | Mean | Standard Deviation | percentage change | Week 24 and Week 96 |
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| Secondary | 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:
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. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 96 weeks |
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| Secondary | 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. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment (Part 2). | Posted | Number | 95% Confidence Interval | percentage of participants | Week 156 |
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| Secondary | 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. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment (Part 2); n=participants who had an assessment at Baseline and given time point. | Posted | Mean | Standard Deviation | seconds | Baseline (Part 1) and Weeks 156, 204 |
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| Secondary | 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. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment (Part 2); n=participants who had an assessment at Baseline and given time point. | Posted | Mean | Standard Deviation | percentage change | Baseline (Part 1) and Weeks 156, 204 |
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| Secondary | 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. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment (Part 2); n=participants who had an assessment at Baseline and given time point. | Posted | Mean | Standard Deviation | seconds | Baseline (Part 1) and Weeks 156, 204 |
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| Secondary | 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. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment (Part 2); n=participants who had an assessment at Baseline and given time point. | Posted | Mean | Standard Deviation | percentage change | Baseline (Part 1) and Weeks 156, 204 |
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| Secondary | 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. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment (Part 2); n=participants who had an assessment at Baseline and given time point. | Posted | Mean | Standard Deviation | seconds | Baseline (Part 1) and Weeks 156, 204 |
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| Secondary | 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. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment (Part 2); n=participants who had an assessment at Baseline and given time point. | Posted | Mean | Standard Deviation | percentage change | Baseline (Part 1) and Weeks 156, 204 |
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| Secondary | 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. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment (Part 2); n=participants who had an assessment at Baseline and given time point. | Posted | Mean | Standard Deviation | units on a scale | Baseline (Part 1) and Weeks 156, 204 |
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| Secondary | 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. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment (Part 2); n=participants who had an assessment at Baseline and given time point. | Posted | Mean | Standard Deviation | percentage change | Baseline (Part 1) and Weeks 156, 204 |
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| Secondary | 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. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment (Part 2); n=participants who had an assessment at Baseline and given time point. | Posted | Mean | Standard Deviation | meters | Baseline (Part 1) and Weeks 156 and 204 |
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| Secondary | 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. | Actual change from baseline tables are provided in previous Outcome Measure. Due to the nature of self-selected population in an extension trial and sparse data on Weeks 204 and 252, further tabulations on percentage changes on these endpoints were deemed less meaningful and unnecessary. | Posted | Baseline (Part 1) and Weeks 156, 204 |
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| Secondary | 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. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment (Part 2) who had an assessment at Baseline and given time point. | Posted | Mean | Standard Deviation | units on a scale | Baseline (Part 1) and Weeks 156 and 204 |
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| Secondary | 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. | Actual change from baseline tables are provided in previous Outcome Measure. Due to the nature of self-selected population in an extension trial and sparse data on Weeks 204 and 252, further tabulations on percentage changes on these endpoints were deemed less meaningful and unnecessary. | Posted | Baseline (Part 1) and Weeks 156, 204 |
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| Secondary | 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). | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment (Part 2). Missing values were imputed using last observation carried forward. | Posted | Mean | Standard Deviation | units on a scale | Baseline (Part 1) and every 4 weeks from Week 108 to Week 204 |
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| Secondary | 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). | Actual change from baseline tables are provided in previous Outcome Measure. Due to the nature of self-selected population in an extension trial and sparse data up to Weeks 204 and 252, further tabulations on percentage changes on these endpoints were deemed less meaningful and unnecessary, and the analysis was not done. | Posted | Baseline (Part 1) and every 4 weeks from Week 108 to Week 204 |
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| Secondary | 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. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment (Part 2) who had an assessment at Baseline and given time point. | Posted | Mean | Standard Deviation | percentage of impairment | Part 2 Baseline (Week 108) and Weeks 156 and 204 |
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| Secondary | 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. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment (Part 2); n=participants who had an assessment at Baseline and given time point. | Posted | Mean | Standard Deviation | percentage change | Part 2 Baseline (Week 108) and Weeks 156 and 204 |
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| Secondary | Part 2: Percentage Change From Week 24 (Part 1) in Whole Brain Volume | Whole brain volume as measured by MRI. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment (Part 2); n=participants who had an assessment at Baseline and given time point. | Posted | Mean | Standard Deviation | percentage change | Week 24 (Part 1) and Weeks 156 and 204 |
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| Secondary | Part 2: Percentage Change From Baseline (Part 1) in Whole Gray Matter Brain Volume | Whole grey matter brain volume as measured by MRI. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment (Part 2); n=participants who had an assessment at Baseline and given time point. | Posted | Mean | Standard Deviation | percentage change | Baseline (Part 1) and Weeks 156 and 204 |
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| Secondary | Part 2: Summary of New/Enlarging T2 Lesion Counts | New or enlarging T2 lesions as measured by MRI. | Intent to treat population: all participants who were randomized and received at least 1 infusion of study treatment (Part 2); n=participants who had an assessment at Baseline and given time point. | Posted | Mean | Standard Deviation | lesions | Baseline (Part 1) up to Week 204 |
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| Secondary | Part 2: Percentage Change From Baseline (Part 1) in Number of New/Enlarging T2 Lesions | New or enlarging T2 lesions as measured by MRI. | Summary new/enlarging T2 lesion values are provided in previous Outcome Measure. Due to the nature of self-selected population in an extension trial and sparse data up to Week 204, further tabulations on percentage changes on these endpoints were deemed less meaningful and unnecessary, and the analysis was not done. | Posted | Baseline (Part 1) and Weeks 156 and 204 |
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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.
Treatment-emergent adverse events only are presented.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
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| EG000 | Placebo | Part 1: participants were randomized to receive placebo IV every 4 weeks for 96 weeks. Part 2: participants transitioned to receive open-label natalizumab 300 mg IV every 4 weeks for at least 96 weeks. | 100 | 449 | 347 | 449 | ||
| EG001 | Natalizumab 300 mg | Part 1: participants were randomized to receive 300 mg of natalizumab IV every 4 weeks for 96 weeks. Part 2: participants transitioned to receive open-label natalizumab 300 mg IV every 4 weeks for at least 96 weeks. | 90 | 439 | 325 | 439 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
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| Anaemia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
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| Acute myocardial infarction | Cardiac disorders | MedDRA 18.0 | Systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | MedDRA 18.0 | Systematic Assessment |
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| Coronary artery disease | Cardiac disorders | MedDRA 18.0 | Systematic Assessment |
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| Tachycardia | Cardiac disorders | MedDRA 18.0 | Systematic Assessment |
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| Pelvic kidney | Congenital, familial and genetic disorders | MedDRA 18.0 | Systematic Assessment |
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| Vertigo positional | Ear and labyrinth disorders | MedDRA 18.0 | Systematic Assessment |
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| Toxic nodular goitre | Endocrine disorders | MedDRA 18.0 | Systematic Assessment |
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| Uveitis | Eye disorders | MedDRA 18.0 | Systematic Assessment |
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| Abdominal hernia | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Colitis | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Duodenal ulcer | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Enteritis | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Gastritis | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Haematemesis | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Hiatus hernia | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Inguinal hernia | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Oesophageal food impaction | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Small intestinal stenosis | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA 18.0 | Systematic Assessment |
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| Catheter site haemorrhage | General disorders | MedDRA 18.0 | Systematic Assessment |
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| Gait disturbance | General disorders | MedDRA 18.0 | Systematic Assessment |
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| Influenza like illness | General disorders | MedDRA 18.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 18.0 | Systematic Assessment |
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| Cholecystitis acute | Hepatobiliary disorders | MedDRA 18.0 | Systematic Assessment |
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| Cholelithiasis | Hepatobiliary disorders | MedDRA 18.0 | Systematic Assessment |
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| Drug-induced liver injury | Hepatobiliary disorders | MedDRA 18.0 | Systematic Assessment |
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| Anaphylactic reaction | Immune system disorders | MedDRA 18.0 | Systematic Assessment |
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| Anaphylactic shock | Immune system disorders | MedDRA 18.0 | Systematic Assessment |
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| Hypersensitivity | Immune system disorders | MedDRA 18.0 | Systematic Assessment |
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| Bacterial sepsis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
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| Brain abscess | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
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| Cellulitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
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| Clostridium difficile colitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
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| Cystitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
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| Enteritis infectious | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
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| H1n1 influenza | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
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| Herpes virus infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
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| Infected dermal cyst | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
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| Infected skin ulcer | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
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| Localised infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Prostatic abscess | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Pyelonephritis acute | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Urinary tract infection enterococcal | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Brain contusion | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Comminuted fracture | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Concussion | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Ear injury | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Extradural haematoma | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Femoral neck fracture | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Fibula fracture | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Foot fracture | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Fractured sacrum | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Head injury | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Multiple fractures | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Overdose | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Postoperative ileus | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Radius fracture | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Soft tissue injury | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Stab wound | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Thermal burn | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Wrist fracture | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 18.0 | Systematic Assessment |
| |
| Diabetic ketoacidosis | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Insulin-requiring type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Obesity | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Type 1 diabetes mellitus | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Foot deformity | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Fracture nonunion | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Rotator cuff syndrome | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
| |
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
| |
| Cholesteatoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
| |
| Colon adenoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
| |
| Lipoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
| |
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
| |
| Pancreatic carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
| |
| Papillary cystadenoma lymphomatosum | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
| |
| Renal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
| |
| Signet-ring cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
| |
| Tonsil cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
| |
| Uterine leiomyoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
| |
| Cerebral venous thrombosis | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Cervical myelopathy | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Generalised tonic-clonic seizure | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Multiple sclerosis | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Multiple sclerosis relapse | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Muscle spasticity | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Optic neuritis | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Quadriparesis | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Secondary progressive multiple sclerosis | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Tonic convulsion | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Transient global amnesia | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Uhthoff's phenomenon | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Abnormal behaviour | Psychiatric disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Acute psychosis | Psychiatric disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Mood disorder due to a general medical condition | Psychiatric disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Substance-induced psychotic disorder | Psychiatric disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Calculus ureteric | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Neurogenic bladder | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Tubulointerstitial nephritis | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Urge incontinence | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Urinary incontinence | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Cervical dysplasia | Reproductive system and breast disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Metrorrhagia | Reproductive system and breast disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Ovarian cyst | Reproductive system and breast disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Sinus polyp | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Erythema multiforme | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Joint surgery | Surgical and medical procedures | MedDRA 18.0 | Systematic Assessment |
| |
| Limb operation | Surgical and medical procedures | MedDRA 18.0 | Systematic Assessment |
| |
| Meniscus operation | Surgical and medical procedures | MedDRA 18.0 | Systematic Assessment |
| |
| Nephrectomy | Surgical and medical procedures | MedDRA 18.0 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Multiple sclerosis relapse | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Muscle spasticity | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
|
Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Biogen Study Medical Director | Biogen | clinicaltrials@biogen.com |
| ID | Term |
|---|---|
| D020528 | Multiple Sclerosis, Chronic Progressive |
| D009362 | Neoplasm Metastasis |
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009385 | Neoplastic Processes |
| D009369 | Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069442 | Natalizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
| Investigator Decision |
|
| Withdrawal by Subject |
|
| Lack of Efficacy |
|
| Lost to Follow-up |
|
| Title | Measurements |
|---|---|
|
| 40 - 49 years |
|
| ≥ 50 years |
|
| Male |
|
| Confirmed on T25FW at 2 years |
|
| Confirmed on 9HPT (either hand) at 2 years |
|
| Confirmed on 9HPT (dominant hand) at 2 years |
|
| Confirmed on 9HPT (non-dominant hand) at 2 years |
|
Confirmed progressors on EDSS |
| Regression, Logistic |
Based on logistic regression, adjusted for Baseline EDSS (<=5.5 or >=6) and/or T25FW and/or 9HPT (either hand). |
| 0.7530 |
| Odds Ratio (OR) |
| 1.06 |
| 2-Sided |
| 95 |
| 0.74 |
| 1.53 |
active/placebo |
| Superiority or Other |
| Confirmed progressors on T25FW | Regression, Logistic | Based on logistic regression, adjusted for Baseline EDSS (<=5.5 or >=6) and/or T25FW and/or 9HPT (either hand). | 0.9137 | Odds Ratio (OR) | 0.98 | 2-Sided | 95 | 0.74 | 1.30 | active/placebo | Superiority or Other |
| Confirmed progressors on 9HPT (either hand) | Regression, Logistic | Based on logistic regression, adjusted for Baseline EDSS (<=5.5 or >=6) and/or T25FW and/or 9HPT (either hand). | 0.0012 | Odds Ratio (OR) | 0.56 | 2-Sided | 95 | 0.40 | 0.80 | Superiority or Other |
| Confirmed progressors on 9HPT (dominant hand) | Regression, Logistic | Based on logistic regression, adjusted for Baseline EDSS (<=5.5 or >=6) and/or T25FW and/or 9HPT (either hand). | 0.1251 | Odds Ratio (OR) | 0.72 | 2-Sided | 95 | 0.48 | 1.09 | Superiority or Other |
| Confirmed progressors on 9HPT (non-dominant hand) | Regression, Logistic | Based on logistic regression, adjusted for Baseline EDSS (<=5.5 or >=6) and/or T25FW and/or 9HPT (either hand). | 0.0091 | Odds Ratio (OR) | 0.58 | 2-Sided | 95 | 0.39 | 0.87 | Superiority or Other |
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Part 1: participants were randomized to receive 300 mg of natalizumab IV every 4 weeks for 96 weeks. Part 2: participants transitioned to receive open-label natalizumab 300 mg IV every 4 weeks for at least 96 weeks.
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