A long term follow up study to look at the progress of patients with symptoms suggestive of MS who took part in previous studies with Betaferon®/Betaseron®

• Register: EUCTR
• Last refreshed on: 29 July 2013
• Main ID: EUCTR2012-005262-35-AT
• Date of registration: 02/04/2013
• Prospective Registration: Yes
• Primary sponsor: Bayer HealthCare AG
• Public title: A long term follow up study to look at the progress of patients with symptoms suggestive of MS who took part in previous studies with Betaferon®/Betaseron®
• Scientific title: BENEFIT 11 a long-term, follow-up study (16401) of the BENEFIT (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 - BENEFIT 11
• Date of first enrolment: 19/07/2013
• Target sample size: 468
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-005262-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Austria, Belgium, Canada, Czech Republic, Denmark, Finland, France, Germany, Hungary, Israel, Italy, Netherlands, Norway, Poland, Portugal, Slovenia, Spain, Sweden, Switzerland, United Kingdom

Contacts

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer HealthCare AG

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer HealthCare AG

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male and female patients with CIS or MS who have been treated at least once in BENEFIT Study 304747.

2. Patients who do not qualify for one or more interventional assessments (eg, MRI due to severe claustrophobia) are invited to participate in the other assessments of this study.

3. Written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 468
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Patients who meet any of the following criteria at the time of screening will be excluded from the study:
? 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.

2. Patients who meet any of the following criteria at the time of screening will be excluded from interventional MRI assessment. However, they should be encouraged to still participate in the study:
? Pregnant or nursing (including pumping for storage and feeding).
? Contraindications to MRI examination (eg, inability to hold breath, severe arrhythmias, very low cardiac output, severe claustrophobia, or patients with implanted defibrillators or other metallic devices not approved for MRI).

3. Patients who meet any of the following criteria at the time of screening will be excluded from contrast media administration. However, they may undergo MRI assessment:
? Contraindication to the use of gadolinium-containing contrast agents (including patients who are suspected for or known to have nephrogenic systemic fibrosis).
? History of severe (as judged by the investigator, taking into account the intensity of the event) allergic or anaphylactoid reaction to any allergen, including drugs and contrast agents.
? Received any contrast agent within 72 hours prior to the study MRI, or scheduled to receive any contrast agent within 72 hours after the study MRI.
? Renal insufficiency, defined by baseline glomerular filtration rate. Estimated value = 30 mL/min/1.73 m2 derived from a serum creatinine result within 2 weeks prior to gadolinium-containing contrast agent injection is needed. Any patient on hemodialysis or peritoneal dialysis is excluded from contrast media administration. If there are multiple creatinine values, the values obtained prior to and closest to the time of the MRI should be used. The core lab value should not be used if not available prior to the MRI.
? Acute renal insufficiency of any intensity, either due to hepato-renal syndrome or occurring in the perioperative liver transplantation period.
? Known history of severe cardiovascular disease (eg, acute myocardial infarction [< 14 days], unstable angina, congestive heart failure New York Heart Association Class IV) or known prolonged QT syndrome.
? Suspected clinical instability or unpredictability of the clinical course during the study (eg, due to previous surgery or acute stroke).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Clinically isolated syndrome (CIS) and multiple sclerosis (MS)
MedDRA version: 14.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 14.1 Level: PT Classification code 10071068 Term: Clinically isolated syndrome System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Trade Name: Betaferon 250 microgram/ml, powder and solvent for solution for injection
Pharmaceutical Form:
INN or Proposed INN: Recombinant interferon beta-1b
Current Sponsor code: BAY86-5046

Primary Outcome(s)

Primary end point(s): Regular face-to-face site visit:
? Relapses
? Conversion to CDMS, to MS by McDonald criteria (2001, 2010), and / or to secondary progressive multiple sclerosis (disease course)
? Expanded Disability Status Scale (EDSS) including DSS 3 and 6 information, Multiple Sclerosis Functional Composite (MSFC) (disability and disability progression) and Multiple Sclerosis Severity Score (MSSS)
? Paced Auditory Serial Addition Test (PASAT) and Symbol Digit Modalities Test (SDMT) (cognitive function)
? Resource use and employment status

Telephone assessment for patients unable to visit site with selected outcomes:
? Relapses
? Telephone EDSS
? Conversion to CDMS (disease course)
? Resource use and vocational status
? Choice of and adherence to MS-specific medication
? Center of Epidemiological Studies Depression Scale (CES-D) (depression)
? Fatigue Scale for Sensory and Motor Functions (FSMC) (fatigue)
? Functional Assessment of Multiple Sclerosis (FAMS) and European Quality of Life - 5 Dimensions (EQ-5D) (QoL)

Timepoint(s) of evaluation of this end point: Relapses, disease course, EDSS milestones and medication history - retrospective assessment since subject's last visit in any of the previous BENEFIT studies up to 11 years.

Resource use - retrospective baseline assessment and 11 year visit.

Cognitive function, depression, fatigue, QoL - cross-sectional assessment (only or in addition to a retrospective assessment) at approximately 11 years after randomization.

Please refer to Figure 4.2 in the Protocol for full details of assessments for the different endpoints in this study.

Main Objective: The primary objectives are to describe the disease course (conversion to clinically-definite multiple sclerosis [CDMS]), change in disability, cognitive function, resource use, and employment status, in relation to treatment with Interferon beta-1b.

Patients that cannot participate in a physical/face-to-face visit will have the option of being assessed via telephone on selected key outcomes, in an attempt to keep the patient ascertainment as high as possible.

Secondary Objective: The secondary objectives are to assess magnetic resonance imaging (MRI) and optical coherence tomography (OCT) parameters, treatment history, quality of life (QoL) parameters, fatigue and depression, the choice of MS-specific medication, and to investigate tolerability of Interferon beta-1b in the full former clinically-isolated syndrome (CIS) cohort as well as in subgroups of patients.

Secondary Outcome(s)

Secondary end point(s): Regular face-to-face site visit:
? Diagnosis and disease course
? MRI parameters
? OCT parameters
? Visual acuity and ophthalmological findings
? CES-D (depression)
? FSMC (fatigue)
? Choice of and adherence to MS-specific medication
? FAMS and EQ-5D (QoL)
? Deoxyribonucleic acid [DNA], ribonucleic acid [RNA], biomarkers
? Vitamin D

Timepoint(s) of evaluation of this end point: Disease course and medication history - retrospective assessment since subject's last visit in any of the previous BENEFIT studies up to 11 years.

MRI, OCT, depression, fatigue, QoL, genetics, evaluation of biomarkers and vitamin D - cross-sectional assessment (only or in addition to a retrospective assessment) at approximately 11 years after randomization.

Please refer to Figure 4.2 in the Protocol for full details of assessments for the different endpoints in this study.

Secondary ID(s)

16401

2012-005262-35-HU

Source(s) of Monetary Support

Bayer HealthCare AG