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

Secondary Progressive Multiple Sclerosis Clinical Trial

— ASCEND in SPMS  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01416181
• Other study ID #: 101MS326
• Secondary ID: 2010-021978-11
• Status: Terminated
• Phase: Phase 3
• First received: July 21, 2011
• Last updated: July 15, 2016
• Start date: September 2011
• Est. completion date: April 2016

Study information

• Verified date: July 2016
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of HealthBelgium: Federal Agency for Medicinal Products and Health ProductsDenmark: Danish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)Ireland: Irish Medicines BoardSpain: Spanish Agency of MedicinesCzech Republic: State Institute for Drug ControlSweden: Medical Products AgencyCanada: Health CanadaUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsUnited States: Food and Drug AdministrationFinland: Finnish Medicines AgencyGermany: Paul-Ehrlich-InstitutRussia: Ministry of Health of the Russian FederationItaly: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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 patient-reported assessments) in participants with SPMS receiving natalizumab treatment for approximately 4 years and to assess change in brain volume and T2 lesion volume.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 889
• Est. completion date: April 2016
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 58 Years

Eligibility

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 (PHI) in accordance with national and local subject privacy regulations.

• Secondary progressive multiple sclerosis (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.

• Expanded Disability Status Scale (EDSS) score of 3.0 to 6.5, inclusive.

• Multiple Sclerosis Severity Score (MSSS) 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 multiple sclerosis (MS) as defined by the revised McDonald Committee criteria.

• Clinical relapse (within 3 months) prior to randomization.

• Timed 25-Foot Walk (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 magnetic resonance imaging (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 (HIV).

• Positive test result for hepatitis C virus (test for hepatitis C virus antibody [HCV Ab]) or hepatitis B virus (test for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb]).

• 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 (PML) 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 (IVIg), or plasmapheresis for treatment of multiple sclerosis 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 Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Neoplasm Metastasis
• Sclerosis
• Secondary Progressive Multiple Sclerosis

Intervention

Drug:
• natalizumab
Administered as specified in the treatment arm
• Placebo
Matched placebo in part 1

Locations

Country	Name	City	State
Belgium	Research Site	La Louviere
Belgium	Research Site	Melsbroek
Belgium	Research Site	Overpelt
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Gatineau	Quebec
Canada	Research Site	Greenfield Park	Quebec
Canada	Research Site	Halifax	Nova Scotia
Canada	Research Site	Kingston	Ontario
Canada	Research Site	London	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
Czech Republic	Research Site	Brno
Czech Republic	Research Site	Hradec Kralove	Bohemia
Czech Republic	Research Site	Olomouc
Czech Republic	Research Site	Praha
Czech Republic	Research Site	Praha
Denmark	Research Site	Arthus C
Denmark	Research Site	Esbjerg
Denmark	Research Site	Glostrup
Denmark	Research Site	København Ø
Denmark	Research Site	Odense
Finland	Research Site	Jyväskylä
Finland	Research Site	Tampere
Finland	Research Site	Turku
France	Research Site	Amiens cedex	Somme
France	Research Site	Bordeaux	Gironde
France	Research Site	Bron cedex	Rhone
France	Research Site	Lille Cedex	Illinois
France	Research Site	Marseille cedex 5	Bouches-du-Rhône
France	Research Site	Nancy	Meurthe et Moselle
France	Research Site	Nantes	Loire Atlantique
France	Research Site	Nice	Alpes Maritimes
Germany	Research Site	Bad Mergentheim	Baden-Wuerttemberg
Germany	Research Site	Bad Wilbad
Germany	Research Site	Dresden	Sachsen
Germany	Research Site	Duesseldorf	Nordrhein Westfalen
Germany	Research Site	Hennigsdorf	Brandenburg
Germany	Research Site	Kassel	Hessen
Germany	Research Site	Muenchen	Bayern
Germany	Research Site	Muenster	Nordrhein Westfalen
Germany	Research Site	Teupitz	Brandenburg
Germany	Research Site	Tuebingen
Ireland	Research Site	Dublin
Ireland	Research Site	Dublin
Israel	Research Site	Jerusalem
Israel	Research Site	Ramat Gan
Italy	Research Site	Baggiovara	Modena
Italy	Research Site	Bari
Italy	Research Site	Cefalu	Palermo
Italy	Research Site	Florence
Italy	Research Site	Gallarate	Varerse
Italy	Research Site	Genova
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	Naples
Italy	Research Site	Napoli
Italy	Research Site	Palermo
Italy	Research Site	Pavia
Italy	Research Site	Rome
Italy	Research Site	Rome
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Hertogenbosch
Netherlands	Research Site	Hoorn
Netherlands	Research Site	Nieuwegein
Netherlands	Research Site	Sittard-Geleen
Poland	Research Site	Bialystok
Poland	Research Site	Gdansk
Poland	Research Site	Katowice
Poland	Research Site	Katowice
Poland	Research Site	Katowice
Poland	Research Site	Krakow
Poland	Research Site	Lodz
Poland	Research Site	Lublin
Poland	Research Site	Olsztyn
Poland	Research Site	Plewiska
Poland	Research Site	Poznan
Poland	Research Site	Szczecin
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa-Miedzylesie
Poland	Research Site	Wroclaw
Russian Federation	Research Site	Belgorod
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	Tyumen
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	El Palmar	Murcia
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Majadahonda	Madrid
Spain	Research Site	Malaga	Málaga
Spain	Research Site	Santa Cruz de Tenerife	Tenerife
Spain	Research Site	Sevilla
Sweden	Research Site	Göteborg
Sweden	Research Site	Örebro
Sweden	Research Site	Stockholm
Sweden	Research Site	Stockholm
Sweden	Research Site	Stockholm
Sweden	Research Site	Umeå
United Kingdom	Research Site	Brighton	West Sussex
United Kingdom	Research Site	Edgbaston	Birmingham
United Kingdom	Research Site	Edinburgh	Lothian Region
United Kingdom	Research Site	Exeter	Devon
United Kingdom	Research Site	Hammersmith	London
United Kingdom	Research Site	Irvine	Ayrshire
United Kingdom	Research Site	Liverpool	Merseyside
United Kingdom	Research Site	London	Greater London
United Kingdom	Research Site	London	Greater London
United Kingdom	Research Site	London	Greater London
United Kingdom	Research Site	Manchester	Greater Manchester
United Kingdom	Research Site	Morriston	Swansea
United Kingdom	Research Site	Newcastle Upon Tyne	Tyne
United Kingdom	Research Site	Norwich	Norfolk
United Kingdom	Research Site	Nottingham	Nottinghamshire
United Kingdom	Research Site	Plymouth	Devon
United Kingdom	Research Site	Sheffield	West Midlands
United States	Research Site	Advance	North Carolina
United States	Research Site	Akron	Ohio
United States	Research Site	Aurora	Colorado
United States	Research Site	Baltimore	Maryland
United States	Research Site	Baltimore	Maryland
United States	Research Site	Burlington	Massachusetts
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Charlottesville	Virginia
United States	Research Site	Chicago	Illinois
United States	Research Site	Clackamas	Oregon
United States	Research Site	Green Bay	Wisconsin
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Kansas City	Kansas
United States	Research Site	Lake Barrington	Illinois
United States	Research Site	Latham	New York
United States	Research Site	Lebanon	New Hampshire
United States	Research Site	Lexington	Kentucky
United States	Research Site	Lexington	Kentucky
United States	Research Site	Los Angeles	California
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Nashville	Tennessee
United States	Research Site	New York	New York
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Omaha	Nebraska
United States	Research Site	Peoria	Illinois
United States	Research Site	Phoenix	Arizona
United States	Research Site	Portland	Oregon
United States	Research Site	Portland	Oregon
United States	Research Site	Raleigh	North Carolina
United States	Research Site	Seattle	Washington
United States	Research Site	Seattle	Washington
United States	Research Site	Tampa	Florida
United States	Research Site	Teaneck	New Jersey
United States	Research Site	Tucson	Arizona
United States	Research Site	Uniontown	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czech Republic,  Denmark,  Finland,  France,  Germany,  Ireland,  Israel,  Italy,  Netherlands,  Poland,  Russian Federation,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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 is defined as one or more of the following criteria, confirmed at a second visit at least 6 months later and at Week 96: • Confirmed progression in EDSS: EDSS score increased from baseline by at least 1 point if baseline EDSS =5.5 or by at least 0.5 points if baseline EDSS =6; • Confirmed progression in T25FW: T25FW increased by at least 20% of the baseline walk; • Confirmed progression in 9HPT: 9HPT increased by at least 20% of the time taken at baseline. The progression in 9HPT can occur on either hand, but will have to be 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.	Up to 96 weeks	No
Primary	The number of participants with Adverse Events (AE) and Serious Adverse Events (SAE)		218 weeks	Yes
Secondary	Part 1: Percentage of participants with a Timed 25-Foot Walk (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 two completed trials.	Up to 96 weeks	No
Secondary	Part 1: Change from Baseline in the 12-Item MS Walking Scale (MSWS-12)	MSWS-12 is a patient 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.	Baseline and Week 96	No
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.	Baseline and Week 96	No
Secondary	Part 1: Change from Baseline in the Multiple Sclerosis Impact Scale-29 Physical (MSIS-29 Physical) score	The 29-item Multiple Sclerosis Impact Scale (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.	Baseline and Week 96	No
Secondary	Part 1: Change from Week 24 in whole brain volume	Whole brain volume will be measured by magnetic resonance imaging	Week 24 and Week 96	No
Secondary	Part 1: Percentage of participants with confirmed worsening in individual Expanded Disability Status Scale (EDSS) Physical 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 meet 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. Worsening must be confirmed on a subsequent examination using the same criterion in the same functional system(s) at least 6 months later.	Up to 96 weeks	No
Secondary	Part 2: Percentage of participants with disability worsening	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.	Up to week 204	No
Secondary	Part 2: Absolute change from Baseline (Part 1) in Timed 25-Foot Walk (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.	Baseline (Part 1) and Weeks 156, 204, and 252	No
Secondary	Part 2: Percentage change from Baseline (Part 2) in Timed 25-Foot Walk (T25FW)		Baseline (Part 1) and Weeks 156, 204, and 252	No
Secondary	Part 2: Absolute change from Baseline (Part 1) in 9-Hole Peg Test (9HPT)	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.	Baseline (Part 1) and Weeks 156, 204, and 252	No
Secondary	Part 2: Percentage change from Baseline (Part 1) in 9-Hole Peg Test (9HPT)		Baseline (Part 1) and Weeks 156, 204, and 252	No
Secondary	Part 2: Absolute change from Baseline (Part 1) in Expanded Disability Status Scale (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.	Baseline (Part 1) and Weeks 156, 204, and 252	No
Secondary	Part 2: Percentage change from Baseline (Part 1) in Expanded Disability Status Scale (EDSS)		Baseline (Part 1) and Weeks 156, 204, and 252	No
Secondary	Part 2: Absolute change from Baseline (Part 1) in the 6-Minute Walk Test (6MWT)	The six-minute walk test (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, and 252	No
Secondary	Part 2: Percentage change from Baseline (Part 1) in the 6-Minute Walk Test (6MWT)		Baseline (Part 1) and Weeks 156, 204, and 252	No
Secondary	Part 2: Absolute change from Baseline (Part 1) in the Multiple Sclerosis Impact Scale-29 Physical (MSIS-29 Physical)	The 29-item Multiple Sclerosis Impact Scale (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.	Baseline (Part 1) and Weeks 156, 204, and 252	No
Secondary	Part 2: Percentage change from Baseline (Part 1) in the Multiple Sclerosis Impact Scale-29 Physical (MSIS-29 Physical)		Baseline (Part 1) and Weeks 156, 204, and 252	No
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).	Baseline (Part 1) and every 4 weeks from Week 108 to Week 252	No
Secondary	Part 2: Percentage change from Baseline (Part 1) in the Symbol Digit Modalities Test (SDMT)		Baseline (Part 1) and every 4 weeks from Week 108 to Week 252	No
Secondary	Part 2: Absolute change from Baseline (Part 2) in the Work Productivity and Activity Impairment - Multiple Sclerosis (WPAI-MS) Questionnaire	The Work Productivity and Activity Impairment (WPAI) questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: 1. Absenteeism (work time missed) 2. Presenteesism (impairment at work / reduced on-the-job effectiveness) 3. Work productivity loss (overall work impairment / absenteeism plus presenteeism) 4. 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, 204 and 252	No
Secondary	Part 2: Percentage change from Baseline (Part 2) in the Work Productivity and Activity Impairment - Multiple Sclerosis (WPAI-MS) Questionnaire		Part 2 Baseline (Week 108) and Weeks 156, 204 and 252	No
Secondary	Part 2: Percentage change from Baseline (Part 1) in whole brain volume	Brain volume will be measured by magnetic resonance imaging (MRI).	Baseline (Part 1) and Weeks 156, 204, and 252	No
Secondary	Part 2: Percentage change from Baseline (Part 1) in gray matter brain volume		Baseline (Part 1) and Weeks 156, 204, and 252	No
Secondary	Part 2: Absolute change from Baseline (Part 1) in number of new/enlarging T2 lesions	Measured by magnetic resonance imaging (MRI).	Baseline (Part 1) and Weeks 156, 204, and 252	No
Secondary	Part 2: Percentage change from Baseline (Part 1) in number of new/enlarging T2 lesions		Baseline (Part 1) and Weeks 156, 204, and 252	No

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