Study Stopped
The ASCEND Study did not achieve statistical significance on the primary or secondary endpoints.
A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis
ASCEND in SPMS
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
2 other identifiers
interventional
889
17 countries
161
Brief Summary
This is a Phase 3b, multicenter, international study conducted in 2 parts. Upon completion of the placebo-controlled period (Part 1), participants will have the option of enrolling in a 2-year open-label extension (Part 2). Part 1: The primary objective of the study is to investigate whether treatment with natalizumab slows the accumulation of disability not related to relapses in participants with secondary progressive multiple sclerosis (SPMS). The secondary objectives of Part 1 of this study are to determine the proportion of participants with consistent improvement in Timed 25-Foot Walk (T25FW), the change in participant-reported ambulatory status as measured by the 12-item MS Walking Scale (MSWS-12), the change in manual ability based on the ABILHAND Questionnaire, the impact of natalizumab on participant-reported quality of life using the Multiple Sclerosis Impact Scale-29 Physical (MSIS-29 Physical), the change in whole brain volume between the end of study and Week 24 using magnetic resonance imaging (MRI) and the proportion of participants experiencing progression of disability as measured by individual physical Expanded Disability Status Scale (EDSS) system scores. Part 2: The primary objective of Part 2 of the study is to evaluate the safety profile of natalizumab in participants with SPMS. The secondary objectives of Part 2 of the study are to investigate long-term disability (based on clinical or participant-reported assessments) in participants with SPMS receiving natalizumab treatment for approximately 4 years and to assess change in brain volume and T2 lesion volume.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Sep 2011
Longer than P75 for phase_3
161 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 21, 2011
CompletedFirst Posted
Study publicly available on registry
August 12, 2011
CompletedStudy Start
First participant enrolled
September 13, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 28, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
April 13, 2016
CompletedResults Posted
Study results publicly available
June 27, 2017
CompletedSeptember 11, 2017
August 1, 2017
3.9 years
July 21, 2011
April 13, 2017
August 10, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Part 1: Percentage of Participants With Confirmed Progression of Disability in One or More of the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), or 9-Hole Peg Test (9HPT)
Confirmed disability progression, defined as ≥1 of the following criteria (confirmed at a second visit ≥6 months later and at Week 96): * Confirmed progression in EDSS (EDSS score increased from baseline \[BL\] by ≥1 point if BL EDSS ≤5.5 or by ≥0.5 points if BL EDSS ≥6); * Confirmed progression in T25FW (T25FW increased by ≥20% of the BL walk); * Confirmed progression in 9HPT (9HPT increased by ≥20% of the time taken at BL on either hand and confirmed on the same hand). The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. The T25FW is a quantitative mobility and leg function performance test where the participant is timed while walking for 25 feet. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs. The 95% confidence interval (CI) of the percentage is based on normal approximation.
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
Secondary Outcomes (27)
Part 1: Percentage of Participants With a T25FW Response
Up to 96 weeks
Part 1: Change From Baseline in the 12-Item MS Walking Scale (MSWS-12)
Baseline and Week 96
Part 1: Change From Baseline in Manual Ability Score Based on the ABILHAND Questionnaire
Baseline and Week 96
Part 1: Change From Baseline in the Multiple Sclerosis Impact Scale-29 Physical (MSIS-29 Physical) Score
Baseline and Week 96
Part 1: Percentage Change From Week 24 in Whole Brain Volume at Week 96
Week 24 and Week 96
- +22 more secondary outcomes
Study Arms (2)
natalizumab
EXPERIMENTALIn 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
EXPERIMENTALIn 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.
Interventions
Administered as specified in the treatment arm
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Biogenlead
Study Sites (161)
Research Site
Phoenix, Arizona, 85013, United States
Research Site
Tucson, Arizona, 85741, United States
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Fullerton, California, 92835, United States
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Los Angeles, California, 90027, United States
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Aurora, Colorado, 80045, United States
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Tampa, Florida, 33612, United States
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Chicago, Illinois, 60637, United States
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Lake Barrington, Illinois, 60010, United States
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Peoria, Illinois, 61606, United States
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Indianapolis, Indiana, 46202, United States
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Indianapolis, Indiana, 46256, United States
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Kansas City, Kansas, 66160, United States
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Lexington, Kentucky, 40513, United States
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Lexington, Kentucky, 40536, United States
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Baltimore, Maryland, 21287, United States
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Burlington, Massachusetts, 01805, United States
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Omaha, Nebraska, 68198, United States
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Lebanon, New Hampshire, 03756, United States
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Teaneck, New Jersey, 07666, United States
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Latham, New York, 12110, United States
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New York, New York, 10029, United States
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Advance, North Carolina, 27006, United States
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Charlotte, North Carolina, 28207, United States
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Raleigh, North Carolina, 27607, United States
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Akron, Ohio, 44320, United States
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Uniontown, Ohio, 44685, United States
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Oklahoma City, Oklahoma, 73104, United States
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Clackamas, Oregon, 97015, United States
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Portland, Oregon, 97225, United States
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Portland, Oregon, 97239, United States
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Nashville, Tennessee, 37215, United States
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Charlottesville, Virginia, 22903, United States
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Seattle, Washington, 98101, United States
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Green Bay, Wisconsin, 54311, United States
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Milwaukee, Wisconsin, 53215, United States
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La Louvière, 7100, Belgium
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Melsbroek, 1820, Belgium
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Overpelt, 3900, Belgium
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Calgary, Alberta, T2N 2T9, Canada
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Edmonton, Alberta, T6G 2G3, Canada
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Vancouver, British Columbia, V6T 1Z3, Canada
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Halifax, Nova Scotia, B3H 4K4, Canada
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Kingston, Ontario, K7L 2V7, Canada
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London, Ontario, N6A 5A5, Canada
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Ottawa, Ontario, K1H 8L6, Canada
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Toronto, Ontario, M4N 3M5, Canada
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Gatineau, Quebec, J9J 0A5, Canada
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Greenfield Park, Quebec, J4V 2J2, Canada
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Montreal, Quebec, H2L 4M1, Canada
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Montreal, Quebec, H3A 2B4, Canada
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Hradec Králové, Bohemia, 50005, Czechia
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Brno, 65691, Czechia
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Olomouc, 77520, Czechia
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Prague, 12111, Czechia
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Arthus C, 8000, Denmark
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Esbjerg, 6700, Denmark
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Glostrup Municipality, 2600, Denmark
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København Ø, 2100, Denmark
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Odense, 5000, Denmark
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Jyväskylä, 40620, Finland
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Tampere, 33520, Finland
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Turku, 20520, Finland
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Nice, Alpes Maritimes, 06002, France
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Marseille, Bouches-du-Rhône, 13385, France
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Nantes, Loire Atlantique, 44093, France
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Nancy, Meurthe et Moselle, 54035, France
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Lille, Nord, 59000, France
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Bron, Rhone, 69677, France
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Salouël, Somme, 80054, France
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Bordeaux, 33076, France
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Bad Mergentheim, Baden-Wurttemberg, 97980, Germany
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Bad Wilbad, Baden-Wurttemberg, 75323, Germany
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Tübingen, Baden-Wurttemberg, 72076, Germany
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Munich, Bavaria, 81377, Germany
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Munich, Bavaria, 81675, Germany
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Hennigsdorf, Brandenburg, 16761, Germany
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Teupitz, Brandenburg, 15755, Germany
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Kassel, Hesse, 34121, Germany
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Düsseldorf, North Rhine-Westphalia, 40225, Germany
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Münster, North Rhine-Westphalia, 48149, Germany
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Dresden, Saxony, 01307, Germany
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Dublin, D4, Ireland
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Dublin, D9, Ireland
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Jerusalem, 91120, Israel
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Ramat Gan, 52621, Israel
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Baggiovara, Modena, 41100, Italy
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Cefalù, Palermo, 90015, Italy
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Gallarate, Varese, 21013, Italy
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Bari, 70124, Italy
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Florence, 50134, Italy
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Genova, 16132, Italy
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Milan, 20122, Italy
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Milan, 20132, Italy
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Naples, 80138, Italy
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Napoli, 80131, Italy
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Palermo, 90146, Italy
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Pavia, 27100, Italy
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Rome, 00176, Italy
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Rome, 00189, Italy
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's-Hertogenbosch, 5223 GZ, Netherlands
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Amsterdam, 1081 HV, Netherlands
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Breda, 4800 RK, Netherlands
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Hoorn, 1624 NP, Netherlands
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Nieuwegein, 3430 EM, Netherlands
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Sittard-Geleen, 6130 MB, Netherlands
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Bialystok, 15-276, Poland
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Gdansk, 80-803, Poland
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Katowice, 40-595, Poland
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Katowice, 40-635, Poland
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Katowice, 40-749, Poland
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Krakow, 31-505, Poland
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Lodz, 90-324, Poland
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Lublin, 20-954, Poland
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Olsztyn, 10-561, Poland
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Plewiska, 62-064, Poland
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Poznan, 61-853, Poland
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Szczecin, 70-111, Poland
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Warsaw, 01-697, Poland
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Warsaw, 02-097, Poland
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Warsaw, 04-141, Poland
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Warszawa-Miedzylesie, 04-749, Poland
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Wroclaw, 50-556, Poland
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Belgorod, 308007, Russia
Research Site
Kazan', 420021, Russia
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Kazan', 420097, Russia
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Moscow, 127015, Russia
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Saint Petersburg, 197110, Russia
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Tyumen, 625000, Russia
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Barcelona, 08035, Spain
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Barcelona, 08036, Spain
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Barcelona, 08041, Spain
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El Palmar, 30120, Spain
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Madrid, 28034, Spain
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Madrid, 28040, Spain
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Majadahonda, 28222, Spain
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Málaga, 29010, Spain
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Santa Cruz de Tenerife, 38010, Spain
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Seville, 41009, Spain
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Gothenburg, 41345, Sweden
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Örebro, 70185, Sweden
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Stockholm, 14186, Sweden
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Stockholm, 17176, Sweden
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Stockholm, 18288, Sweden
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Umeå, 90185, Sweden
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Irvine, Ayrshire, KA12 8SS, United Kingdom
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Edgbaston, Birmingham, B15 2TH, United Kingdom
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Exeter, Devon, EX2 5DW, United Kingdom
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Plymouth, Devon, PL6 8BX, United Kingdom
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London, Greater London, E1 2AT, United Kingdom
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London, Greater London, SE5 9RS, United Kingdom
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Hammersmith, London, W6 8RF, United Kingdom
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Edinburgh, Lothian Region, EH4 2XU, United Kingdom
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Salford, Manchester, M6 8HD, United Kingdom
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Liverpool, Merseyside, L9 7LJ, United Kingdom
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Norwich, Norfolk, NR4 7UY, United Kingdom
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Nottingham, Nottinghamshire, NG7 2UH, United Kingdom
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Morriston, Swansea, SA6 6NL, United Kingdom
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Newcastle, Tyne, NE1 4LP, United Kingdom
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Brighton, BN2 5BE, United Kingdom
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London, WC1N 3BG, United Kingdom
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Sheffield, S10 2JF, United Kingdom
Related Publications (4)
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.
PMID: 37652990DERIVEDBeynon 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.
PMID: 35720980DERIVEDKoch 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.
PMID: 34376508DERIVEDKapoor 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.
PMID: 29545067DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Biogen Study Medical Director
- Organization
- Biogen
Study Officials
- STUDY DIRECTOR
Medical Director
Biogen
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 21, 2011
First Posted
August 12, 2011
Study Start
September 13, 2011
Primary Completion
July 28, 2015
Study Completion
April 13, 2016
Last Updated
September 11, 2017
Results First Posted
June 27, 2017
Record last verified: 2017-08