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

10 августа 2017 г. обновлено: Biogen

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy of Natalizumab on Reducing Disability Progression in Subjects With Secondary Progressive Multiple Sclerosis, With Optional Open-Label Extension

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.

Обзор исследования

Статус

Прекращено

Условия

Вмешательство/лечение

Тип исследования

Интервенционный

Регистрация (Действительный)

889

Фаза

  • Фаза 3

Контакты и местонахождение

В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.

Места учебы

  • Бельгия
      • La Louviere, Бельгия, 7100
        • Research Site
      • Melsbroek, Бельгия, 1820
        • Research Site
      • Overpelt, Бельгия, 3900
        • Research Site
  • Германия
    • Baden Wuerttemberg
      • Bad Wilbad, Baden Wuerttemberg, Германия, 75323
        • Research Site
      • Tuebingen, Baden Wuerttemberg, Германия, 72076
        • Research Site
    • Baden-Wuerttemberg
      • Bad Mergentheim, Baden-Wuerttemberg, Германия, 97980
        • Research Site
    • Bayern
      • Muenchen, Bayern, Германия, 81675
        • Research Site
      • Muenchen, Bayern, Германия, 81377
        • Research Site
    • Brandenburg
      • Hennigsdorf, Brandenburg, Германия, 16761
        • Research Site
      • Teupitz, Brandenburg, Германия, 15755
        • Research Site
    • Hessen
      • Kassel, Hessen, Германия, 34121
        • Research Site
    • Nordrhein Westfalen
      • Duesseldorf, Nordrhein Westfalen, Германия, 40225
        • Research Site
      • Muenster, Nordrhein Westfalen, Германия, 48149
        • Research Site
    • Sachsen
      • Dresden, Sachsen, Германия, 01307
        • Research Site
  • Дания
      • Arthus C, Дания, 8000
        • Research Site
      • Esbjerg, Дания, 6700
        • Research Site
      • Glostrup, Дания, 2600
        • Research Site
      • København Ø, Дания, 2100
        • Research Site
      • Odense, Дания, 5000
        • Research Site
  • Израиль
      • Jerusalem, Израиль, 91120
        • Research Site
      • Ramat Gan, Израиль, 52621
        • Research Site
  • Ирландия
      • Dublin, Ирландия, D4
        • Research Site
      • Dublin, Ирландия, D9
        • Research Site
  • Испания
      • Barcelona, Испания, 08035
        • Research Site
      • Barcelona, Испания, 08036
        • Research Site
      • Barcelona, Испания, 08041
        • Research Site
      • El Palmar, Испания, 30120
        • Research Site
      • Madrid, Испания, 28034
        • Research Site
      • Madrid, Испания, 28040
        • Research Site
      • Majadahonda, Испания, 28222
        • Research Site
      • Málaga, Испания, 29010
        • Research Site
      • Santa Cruz de Tenerife, Испания, 38010
        • Research Site
      • Sevilla, Испания, 41009
        • Research Site
  • Италия
      • Bari, Италия, 70124
        • Research Site
      • Florence, Италия, 50134
        • Research Site
      • Genova, Италия, 16132
        • Research Site
      • Milano, Италия, 20122
        • Research Site
      • Milano, Италия, 20132
        • Research Site
      • Naples, Италия, 80138
        • Research Site
      • Napoli, Италия, 80131
        • Research Site
      • Palermo, Италия, 90146
        • Research Site
      • Pavia, Италия, 27100
        • Research Site
      • Rome, Италия, 00189
        • Research Site
      • Rome, Италия, 00176
        • Research Site
    • Modena
      • Baggiovara, Modena, Италия, 41100
        • Research Site
    • Palermo
      • Cefalu, Palermo, Италия, 90015
        • Research Site
    • Varese
      • Gallarate, Varese, Италия, 21013
        • Research Site
  • Канада
    • Alberta
      • Calgary, Alberta, Канада, T2N 2T9
        • Research Site
      • Edmonton, Alberta, Канада, T6G 2G3
        • Research Site
    • British Columbia
      • Vancouver, British Columbia, Канада, V6T 1Z3
        • Research Site
    • Nova Scotia
      • Halifax, Nova Scotia, Канада, B3H 4K4
        • Research Site
    • Ontario
      • Kingston, Ontario, Канада, K7L 2V7
        • Research Site
      • London, Ontario, Канада, N6A 5A5
        • Research Site
      • Ottawa, Ontario, Канада, K1H 8L6
        • Research Site
      • Toronto, Ontario, Канада, M4N 3M5
        • Research Site
    • Quebec
      • Gatineau, Quebec, Канада, J9J 0A5
        • Research Site
      • Greenfield Park, Quebec, Канада, J4V 2J2
        • Research Site
      • Montreal, Quebec, Канада, H2L 4M1
        • Research Site
      • Montreal, Quebec, Канада, H3A 2B4
        • Research Site
  • Нидерланды
      • Amsterdam, Нидерланды, 1081 HV
        • Research Site
      • Breda, Нидерланды, 4800 RK
        • Research Site
      • Hertogenbosch, Нидерланды, 5223 GZ
        • Research Site
      • Hoorn, Нидерланды, 1624 NP
        • Research Site
      • Nieuwegein, Нидерланды, 3430 EM
        • Research Site
      • Sittard-Geleen, Нидерланды, 6130 MB
        • Research Site
  • Польша
      • Bialystok, Польша, 15-276
        • Research Site
      • Gdansk, Польша, 80-803
        • Research Site
      • Katowice, Польша, 40-749
        • Research Site
      • Katowice, Польша, 40-595
        • Research Site
      • Katowice, Польша, 40-635
        • Research Site
      • Krakow, Польша, 31-505
        • Research Site
      • Lodz, Польша, 90-324
        • Research Site
      • Lublin, Польша, 20-954
        • Research Site
      • Olsztyn, Польша, 10-561
        • Research Site
      • Plewiska, Польша, 62-064
        • Research Site
      • Poznan, Польша, 61-853
        • Research Site
      • Szczecin, Польша, 70-111
        • Research Site
      • Warszawa, Польша, 04-141
        • Research Site
      • Warszawa, Польша, 02-097
        • Research Site
      • Warszawa, Польша, 01-697
        • Research Site
      • Warszawa-Miedzylesie, Польша, 04-749
        • Research Site
      • Wroclaw, Польша, 50-556
        • Research Site
  • Российская Федерация
      • Belgorod, Российская Федерация, 308007
        • Research Site
      • Kazan, Российская Федерация, 420021
        • Research Site
      • Kazan, Российская Федерация, 420097
        • Research Site
      • Moscow, Российская Федерация, 127015
        • Research Site
      • St. Petersburg, Российская Федерация, 197110
        • Research Site
      • Tyumen, Российская Федерация, 625000
        • Research Site
  • Соединенное Королевство
      • Brighton, Соединенное Королевство, BN2 5BE
        • Research Site
      • London, Соединенное Королевство, WC1N 3BG
        • Research Site
      • Sheffield, Соединенное Королевство, S10 2JF
        • Research Site
    • Ayrshire
      • Irvine, Ayrshire, Соединенное Королевство, KA12 8SS
        • Research Site
    • Birmingham
      • Edgbaston, Birmingham, Соединенное Королевство, B15 2TH
        • Research Site
    • Devon
      • Exeter, Devon, Соединенное Королевство, EX2 5DW
        • Research Site
      • Plymouth, Devon, Соединенное Королевство, PL6 8BX
        • Research Site
    • Greater London
      • London, Greater London, Соединенное Королевство, SE5 9RS
        • Research Site
      • London, Greater London, Соединенное Королевство, E1 2AT
        • Research Site
    • London
      • Hammersmith, London, Соединенное Королевство, W6 8RF
        • Research Site
    • Lothian Region
      • Edinburgh, Lothian Region, Соединенное Королевство, EH4 2XU
        • Research Site
    • Manchester
      • Salford, Manchester, Соединенное Королевство, M6 8HD
        • Research Site
    • Merseyside
      • Liverpool, Merseyside, Соединенное Королевство, L9 7LJ
        • Research Site
    • Norfolk
      • Norwich, Norfolk, Соединенное Королевство, NR4 7UY
        • Research Site
    • Nottinghamshire
      • Nottingham, Nottinghamshire, Соединенное Королевство, NG7 2UH
        • Research Site
    • Swansea
      • Morriston, Swansea, Соединенное Королевство, SA6 6NL
        • Research Site
    • Tyne
      • Newcastle, Tyne, Соединенное Королевство, NE1 4LP
        • Research Site
  • Соединенные Штаты
    • Arizona
      • Phoenix, Arizona, Соединенные Штаты, 85013
        • Research Site
      • Tucson, Arizona, Соединенные Штаты, 85741
        • Research Site
    • California
      • Fullerton, California, Соединенные Штаты, 92835
        • Research Site
      • Los Angeles, California, Соединенные Штаты, 90027
        • Research Site
    • Colorado
      • Aurora, Colorado, Соединенные Штаты, 80045
        • Research Site
    • Florida
      • Tampa, Florida, Соединенные Штаты, 33612
        • Research Site
    • Illinois
      • Chicago, Illinois, Соединенные Штаты, 60637
        • Research Site
      • Lake Barrington, Illinois, Соединенные Штаты, 60010
        • Research Site
      • Peoria, Illinois, Соединенные Штаты, 61606
        • Research Site
    • Indiana
      • Indianapolis, Indiana, Соединенные Штаты, 46202
        • Research Site
      • Indianapolis, Indiana, Соединенные Штаты, 46256
        • Research Site
    • Kansas
      • Kansas City, Kansas, Соединенные Штаты, 66160
        • Research Site
    • Kentucky
      • Lexington, Kentucky, Соединенные Штаты, 40536
        • Research Site
      • Lexington, Kentucky, Соединенные Штаты, 40513
        • Research Site
    • Maryland
      • Baltimore, Maryland, Соединенные Штаты, 21287
        • Research Site
    • Massachusetts
      • Burlington, Massachusetts, Соединенные Штаты, 01805
        • Research Site
    • Nebraska
      • Omaha, Nebraska, Соединенные Штаты, 68198
        • Research Site
    • New Hampshire
      • Lebanon, New Hampshire, Соединенные Штаты, 03756
        • Research Site
    • New Jersey
      • Teaneck, New Jersey, Соединенные Штаты, 07666
        • Research Site
    • New York
      • Latham, New York, Соединенные Штаты, 12110
        • Research Site
      • New York, New York, Соединенные Штаты, 10029
        • Research Site
    • North Carolina
      • Advance, North Carolina, Соединенные Штаты, 27006
        • Research Site
      • Charlotte, North Carolina, Соединенные Штаты, 28207
        • Research Site
      • Raleigh, North Carolina, Соединенные Штаты, 27607
        • Research Site
    • Ohio
      • Akron, Ohio, Соединенные Штаты, 44320
        • Research Site
      • Uniontown, Ohio, Соединенные Штаты, 44685
        • Research Site
    • Oklahoma
      • Oklahoma City, Oklahoma, Соединенные Штаты, 73104
        • Research Site
    • Oregon
      • Clackamas, Oregon, Соединенные Штаты, 97015
        • Research Site
      • Portland, Oregon, Соединенные Штаты, 97239
        • Research Site
      • Portland, Oregon, Соединенные Штаты, 97225
        • Research Site
    • Tennessee
      • Nashville, Tennessee, Соединенные Штаты, 37215
        • Research Site
    • Virginia
      • Charlottesville, Virginia, Соединенные Штаты, 22903
        • Research Site
    • Washington
      • Seattle, Washington, Соединенные Штаты, 98101
        • Research Site
    • Wisconsin
      • Green Bay, Wisconsin, Соединенные Штаты, 54311
        • Research Site
      • Milwaukee, Wisconsin, Соединенные Штаты, 53215
        • Research Site
  • Финляндия
      • Jyväskylä, Финляндия, 40620
        • Research Site
      • Tampere, Финляндия, 33520
        • Research Site
      • Turku, Финляндия, 20520
        • Research Site
  • Франция
      • Bordeaux, Франция, 33076
        • Research Site
    • Alpes Maritimes
      • Nice, Alpes Maritimes, Франция, 06002
        • Research Site
    • Bouches-du-Rhône
      • Marseille cedex 5, Bouches-du-Rhône, Франция, 13385
        • Research Site
    • Loire Atlantique
      • Nantes, Loire Atlantique, Франция, 44093
        • Research Site
    • Meurthe et Moselle
      • Nancy, Meurthe et Moselle, Франция, 54035
        • Research Site
    • Nord
      • Lille Cedex, Nord, Франция, 59000
        • Research Site
    • Rhone
      • Bron cedex, Rhone, Франция, 69677
        • Research Site
    • Somme
      • Salouel, Somme, Франция, 80054
        • Research Site
  • Чехия
      • Brno, Чехия, 65691
        • Research Site
      • Olomouc, Чехия, 77520
        • Research Site
      • Praha, Чехия, 12111
        • Research Site
    • Bohemia
      • Hradec Kralove, Bohemia, Чехия, 50005
        • Research Site
  • Швеция
      • Göteborg, Швеция, 41345
        • Research Site
      • Stockholm, Швеция, 17176
        • Research Site
      • Stockholm, Швеция, 14186
        • Research Site
      • Stockholm, Швеция, 18288
        • Research Site
      • Umeå, Швеция, 90185
        • Research Site
      • Örebro, Швеция, 70185
        • Research Site

Критерии участия

Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.

Критерии приемлемости

Возраст, подходящий для обучения

От 18 лет до 58 лет (Взрослый)

Принимает здоровых добровольцев

Нет

Полы, имеющие право на обучение

Все

Описание

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.

Учебный план

В этом разделе представлена ​​подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.

Как устроено исследование?

Детали дизайна

  • Основная цель: Уход
  • Распределение: Рандомизированный
  • Интервенционная модель: Параллельное назначение
  • Маскировка: Тройной

Оружие и интервенции

Группа участников / Армия
Вмешательство/лечение
Экспериментальный: 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.
Лекарство: натализумаб
Вводят, как указано в лечебной группе
Другие имена:
  • Тисабри
  • BG00002
Экспериментальный: 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.
Лекарство: натализумаб
Вводят, как указано в лечебной группе
Другие имена:
  • Тисабри
  • BG00002
Лекарство: Placebo
Matched placebo in part 1

Что измеряет исследование?

Первичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
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)
Временное ограничение: Up to 96 weeks (2 years)

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.
Up to 96 weeks (2 years)
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Временное ограничение: 218 weeks
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

Вторичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Part 1: Percentage of Participants With a T25FW Response
Временное ограничение: Up to 96 weeks
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.
Up to 96 weeks
Part 1: Change From Baseline in the 12-Item MS Walking Scale (MSWS-12)
Временное ограничение: Baseline and Week 96
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
Временное ограничение: Baseline and Week 96
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
Временное ограничение: Baseline and Week 96
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
Временное ограничение: Week 24 and 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
Временное ограничение: Up to 96 weeks

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.
Up to 96 weeks
Part 2: Percentage of Participants With Disability Worsening at 156 Weeks
Временное ограничение: Week 156
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
Временное ограничение: Baseline (Part 1) and Weeks 156, 204
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
Временное ограничение: Baseline (Part 1) and Weeks 156, 204
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)
Временное ограничение: Baseline (Part 1) and Weeks 156, 204
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)
Временное ограничение: Baseline (Part 1) and Weeks 156, 204
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)
Временное ограничение: Baseline (Part 1) and Weeks 156, 204
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)
Временное ограничение: Baseline (Part 1) and Weeks 156, 204
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
Временное ограничение: Baseline (Part 1) and Weeks 156, 204
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
Временное ограничение: Baseline (Part 1) and Weeks 156, 204
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)
Временное ограничение: Baseline (Part 1) and Weeks 156 and 204
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
Временное ограничение: Baseline (Part 1) and Weeks 156, 204
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
Временное ограничение: Baseline (Part 1) and Weeks 156 and 204
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
Временное ограничение: Baseline (Part 1) and Weeks 156, 204
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)
Временное ограничение: Baseline (Part 1) and every 4 weeks from Week 108 to Week 204
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
Временное ограничение: Baseline (Part 1) and every 4 weeks from Week 108 to Week 204
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
Временное ограничение: Part 2 Baseline (Week 108) and Weeks 156 and 204
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
Временное ограничение: Part 2 Baseline (Week 108) and Weeks 156 and 204
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
Временное ограничение: Week 24 (Part 1) and Weeks 156 and 204
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
Временное ограничение: Baseline (Part 1) and Weeks 156 and 204
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
Временное ограничение: Baseline (Part 1) up to Week 204
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
Временное ограничение: Baseline (Part 1) and Weeks 156 and 204
New or enlarging T2 lesions as measured by MRI.
Baseline (Part 1) and Weeks 156 and 204

Соавторы и исследователи

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Спонсор

Biogen

Публикации и полезные ссылки

Лицо, ответственное за внесение сведений об исследовании, добровольно предоставляет эти публикации. Это может быть что угодно, связанное с исследованием.

Общие публикации

Полезные ссылки

Даты записи исследования

Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.

Изучение основных дат

Начало исследования (Действительный)

13 сентября 2011 г.

Первичное завершение (Действительный)

28 июля 2015 г.

Завершение исследования (Действительный)

13 апреля 2016 г.

Даты регистрации исследования

Первый отправленный

21 июля 2011 г.

Впервые представлено, что соответствует критериям контроля качества

11 августа 2011 г.

Первый опубликованный (Оценивать)

12 августа 2011 г.

Обновления учебных записей

Последнее опубликованное обновление (Действительный)

11 сентября 2017 г.

Последнее отправленное обновление, отвечающее критериям контроля качества

10 августа 2017 г.

Последняя проверка

1 августа 2017 г.

Дополнительная информация

Термины, связанные с этим исследованием

Ключевые слова

Дополнительные соответствующие термины MeSH

Другие идентификационные номера исследования

  • 101MS326
  • 2010-021978-11 (Номер EudraCT)

Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .

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