Clinical trial NCT01795872: Follow-up Study After 11 Years of Patients Who Were Included in the BENEFIT Trial (304747) With a First Demyelinating Event Suggestive of Multiple Sclerosis
Official title: BENEFIT 11 a Long-term Follow-up Study of the BENEFIT (Betaferon/Betaseron in Newly Emerging Multiple Sclerosis for Initial Treatment, 304747), BENEFIT Follow-up (305207) Studies and BENEFIT Extension (311129) Study to Further Evaluate the Progress of Patients With First Demyelinating Event Suggestive of Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Multiple Sclerosis
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2013-02-21
Enrollment: 278
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study assesses clinical and imaging long-term data, after early or delayed interferon-beta-1b treatment in patients with a first demyelinating event suggestive of multiple sclerosis (MS), 11 years after enrollment in the Betaferon/Betaseron in Newly Emerging Multiple Sclerosis for Initial Treatment (BENEFIT) study (304747). The main objectives are to describe the disease course, change in disability, cognitive function, resource use and employment status, in relation to Interferon beta-1b in the long term.

Detailed description: As optic coherence tomography (OCT) and magnetic resonance imaging (MRI) studies are essential to standardize the procedures and assessments for all OCT and MRI test centers that may take part in this study, 122 additional volunteers will be enrolled to test the dummy scans of OCT and MRI, only.

Eligibility criteria: Inclusion Criteria:

* Male and female patients with clinical-isolated syndrome or multiple sclerosis who have been treated at least once in BENEFIT Study 304747

Exclusion Criteria:

* Patients who, according to the investigator's judgment, have medical, psychiatric, or other conditions that compromise the patient's ability to understand the purpose of the study

Primary outcomes:
measure: Time to First Relapse by Kaplan-Meier Estimates
timeFrame: Up to Year 11 (Day 3960)
measure: Time to Clinically Definite Multiple Sclerosis (CDMS) Represented by Kaplan-Meier Estimates
timeFrame: Up to Year 11 (Day 3960)
measure: Number of Subjects With Diagnosis of Multiple Sclerosis Within Eleven years after Clinically-Isolated Syndrome (CIS) According to McDonald 2001 and 2010 Criteria
timeFrame: Year 11
measure: Disease Course as Assessed at the Time of BENEFIT 11
timeFrame: Year 11
measure: Percentage of Subjects Converting to Secondary Progressive Multiple Sclerosis (SPMS)
timeFrame: Year 11
measure: Time to Secondary Progressive Multiple Sclerosis (SPMS) Represented by Kaplan-Meier Estimates
timeFrame: Up to Year 11 (Day 3960)
measure: Expanded Disability Status Scale (EDSS) at Year 11
timeFrame: Year 11
measure: Number of Subjects With Confirmed and Sustained 1-point Expanded Disability Status Scale (EDSS) Progression at Year 11
timeFrame: Year 11
measure: Number of Subjects With Confirmed 2.5-point Expanded Disability Status Scale (EDSS) Progression at Year 11
timeFrame: Year 11
measure: Percentage of Subjects who Ever Reached a Disability Status Scale (DSS) 3 and 6
timeFrame: Year 11
measure: Disability Based Efficacy Domain: Time to Disability Status Scale (DSS) 3 by Kaplan-Meier Estimates
timeFrame: Up to Year 11 (Day 3960)
measure: Disability Based Efficacy Domain: Time to Disability Status Scale (DSS) 6 by Kaplan-Meier Estimates
timeFrame: Up to Year 11 (Day 3960)
measure: Multiple Sclerosis Functional Composite (MSFC) at Year 11
timeFrame: Year 11
measure: Multiple Sclerosis Severity Score (MSSS) at Year 11
timeFrame: Year 11
measure: Cognitive Function: Paced Auditory Serial Addition Test-3 (PASAT-3) at Year 11
timeFrame: Year 11
measure: Cognitive function: Symbol Digit Modalities Test (SDMT)
timeFrame: Year 11
measure: Relapse-Based Efficacy domain: Hazard Ratio for Recurrent Relapses
timeFrame: Year 11
measure: Relapse Based Efficacy Domain: Annualized Relapse Rate
timeFrame: Year 11
measure: Time to use of Ambulatory Device Represented by Kaplan-Meier Estimates
timeFrame: Up to Year 11 (Day 3960)
measure: Time to Dependence of Ambulatory Device for Walking Represented by Kaplan-Meier Estimates
timeFrame: Up to Year 11 (Day 3960)
measure: Number of Subjects With Wheelchair Use After 11 years
timeFrame: Year 11
Secondary outcomes:
measure: Education Status at Year 11
timeFrame: Year 11
measure: Living Conditions at Year 11
timeFrame: Year 11
measure: Employment Status at Year 11
timeFrame: Year 11
measure: Multiple Sclerosis Impact on Employment at Year 11
timeFrame: Year 11
measure: Resource Use: Hospitalization During Last 12 months
timeFrame: Year 11
measure: Resource Use: Visits to Other Specialists During Last 12 months
timeFrame: Year 11
measure: Resource Use Assessment Questionnaire: Help from Family/Regular Ambulatory Services
timeFrame: Year 11
measure: Resource Use Assessment Questionnaire: Additional Ambulatory Services During Relapse
timeFrame: Year 11
measure: Resource Use Assessment Questionnaire: Adaptions past 6 months
timeFrame: Year 11
measure: Patient-Reported Outcomes (PRO)-based Efficacy Domain: Center of Epidemiological Studies Depression Scale (CES-D) Total Score at Year 11
timeFrame: Year 11
measure: PRO-based Efficacy Domain: Fatigue Scale for Sensory and Motor Functions (FSMC)
timeFrame: Year 11
measure: Functional Assessment of Multiple Sclerosis (FAMS) Trial Outcome Index (TOI) at Year 11
timeFrame: Year 11
measure: Functional Assessment of Multiple Sclerosis (FAMS) Total Score at Year 11
timeFrame: Year 11
measure: PRO-based Efficacy Domain: European Quality of Life - 5 Dimensions (EQ-5D) Score at Year 11
timeFrame: Year 11
measure: European Quality of Life - 5 Dimensions (EQ-5D) Health-related quality of life (HRQoL) Score at Year 11
timeFrame: Year 11
measure: Number of Subjects who Started Second Line Therapy at Year 11
timeFrame: Year 11
measure: Number of Subjects who Started First Disease-Modifying Treatment (DMT) other than IFNB at Year 11
timeFrame: Year 11
measure: Magnet-Resonance Imaging (MRI): Number of Newly Active Lesions
timeFrame: Year 11
measure: Magnet-Resonance Imaging (MRI): Number of Lesions on T1- and T2-Weighted Scans
timeFrame: Year 11
measure: Magnet-Resonance Imaging (MRI): Volume of Lesions on T1- and T2-Weighted Scans
timeFrame: Year 11
measure: Magnet-Resonance Imaging (MRI): Normalized Brain Volume
timeFrame: Year 11
measure: Optical Coherence Tomography (OCT) Parameter - Retinal Nerve Fiber Layer (RNFL)
timeFrame: Year 11
measure: Optical Coherence Tomography (OCT) Parameter - Total Macular Volume (TMV)
timeFrame: Year 11
measure: Optical Coherence Tomography (OCT) Parameter - Pupillo Macular Bundle (PMB)
timeFrame: Year 11
measure: Optical Coherence Tomography (OCT) Parameter - Ganglion Cell Inner Plexiform Layer
timeFrame: Year 11
measure: Ophthalmological examination - Optic Nerve Head
timeFrame: Year 11
measure: Ophthalmological examination - Slit lamp Biomicroscopy
timeFrame: Year 11
measure: Ophthalmological examination - Visual Acuity
timeFrame: Year 11
measure: Number of Subjects with Vitamin D Intake
timeFrame: Year 11
Other outcomes:
Locations:
city: Graz
country: Austria
state: Steiermark
city: Innsbruck
country: Austria
city: Bruxelles - Brussel
country: Belgium
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Calgary
country: Canada
state: Alberta
city: London
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Brno
country: Czech Republic
city: Hradec Kralove
country: Czech Republic
city: Ostrava-Poruba
country: Czech Republic
city: Praha 2
country: Czech Republic
city: Glostrup
country: Denmark
city: Oulu
country: Finland
city: Seinäjoki
country: Finland
city: Tampere
country: Finland
city: Turku
country: Finland
city: Bordeaux
country: France
city: Clermont ferrand
country: France
city: Dijon
country: France
city: Lille
country: France
city: Nice
country: France
city: Rennes
country: France
city: Toulouse
country: France
city: Ulm
country: Germany
state: Baden-Württemberg
city: München
country: Germany
state: Bayern
city: Regensburg
country: Germany
state: Bayern
city: Würzburg
country: Germany
state: Bayern
city: Hennigsdorf
country: Germany
state: Brandenburg
city: Gießen
country: Germany
state: Hessen
city: Marburg
country: Germany
state: Hessen
city: Offenbach
country: Germany
state: Hessen
city: Greifswald
country: Germany
state: Mecklenburg-Vorpommern
city: Göttingen
country: Germany
state: Niedersachsen
city: Düsseldorf
country: Germany
state: Nordrhein-Westfalen
city: Köln
country: Germany
state: Nordrhein-Westfalen
city: Mainz
country: Germany
state: Rheinland-Pfalz
city: Halle
country: Germany
state: Sachsen-Anhalt
city: Erfurt
country: Germany
state: Thüringen
city: Münster
country: Germany
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Szeged
country: Hungary
city: Jerusalem
country: Israel
city: Tel Hashomer
country: Israel
city: Orbassano
country: Italy
state: Torino
city: Gallarate
country: Italy
city: Milano
country: Italy
city: Padova
country: Italy
city: Pavia
country: Italy
city: Torino
country: Italy
city: Sittard
country: Netherlands
city: Bergen
country: Norway
city: Bydgoszcz
country: Poland
city: Krakow
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Wroclaw
country: Poland
city: Coimbra
country: Portugal
city: Ljubljana
country: Slovenia
city: Sevilla
country: Spain
state: Andalucía
city: L'Hospitalet de Llobregat
country: Spain
state: Barcelona
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Málaga
country: Spain
city: Valencia
country: Spain
city: Göteborg
country: Sweden
city: Basel
country: Switzerland
state: Basel-Stadt
city: St. Gallen
country: Switzerland
state: Sankt Gallen
city: Bern
country: Switzerland
city: Sheffield
country: United Kingdom
state: South Yorkshire
city: Aberdeen
country: United Kingdom
city: Dundee
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Kappos L, Edan G, Freedman MS, Montalban X, Hartung HP, Hemmer B, Fox EJ, Barkhof F, Schippling S, Schulze A, Pleimes D, Pohl C, Sandbrink R, Suarez G, Wicklein EM; BENEFIT Study Group. The 11-year long-term follow-up study from the randomized BENEFIT CIS trial. Neurology. 2016 Sep 6;87(10):978-87. doi: 10.1212/WNL.0000000000003078. Epub 2016 Aug 10.