Observational Study of Tysabri® in Early Relapsing-Remitting Multiple Sclerosis in Anti-JC Virus (JCV) Antibody Negative Participants (STRIVE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Biogen Idec
Sponsor:
Information provided by (Responsible Party):
Biogen Idec
ClinicalTrials.gov Identifier:
NCT01485003
First received: December 1, 2011
Last updated: September 19, 2014
Last verified: September 2014
  Purpose

The primary objective of the study is to determine which baseline and yearly response factors (clinical and para clinical) predict overall disease-free status at Month 12 and Month 24, and clinical disease-free status in subsequent Months 36 and 48. The response factors include clinical assessments of sustained Expanded Disability Status Scale (EDSS) progression, relapse status, and magnetic resonance image (MRI) measures, and participant reported outcomes (PROs) of cognition, capacity to work, quality of life (QoL), and visual function assessments.


Condition
Relapsing-Remitting Multiple Sclerosis

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: A Multicenter, Observational, Open-Label, Single-Arm Study of Tysabri in Early Relapsing-Remitting Multiple Sclerosis in Anti-JCV Antibody Negative Patients.

Resource links provided by NLM:


Further study details as provided by Biogen Idec:

Primary Outcome Measures:
  • Percentage of Participants who are overall disease activity-free at Months 12 and 24 [ Time Frame: Baseline and Months 12 and 24 ] [ Designated as safety issue: No ]
    Overall disease activity-free is defined as no relapses, no disability progression (RRMS), and absence of magnetic resonance imaging (MRI) disease activity (no gadolinium [gd])+ lesions, no new or enlarging T2-hyperintense lesions). A clinical relapse is defined as new or recurrent neurological symptoms, not associated with fever, lasting for at least 24 hours, and followed by a period of 30 days of stability or improvement. Sustained disability progression defined by at least a 1.0-point increase on the Expanded Disability Status Scale (EDSS) from a Baseline EDSS ≥1.0 that is sustained for 12 or 24 weeks, or at least a 1.5-point increase on the EDSS from a Baseline EDSS <1.0 that is sustained for 12 or 24 weeks. The EDSS measures the disability status of people with multiple sclerosis on a scale that ranges from 0 to 10, with higher scores indicating more disability.

  • Percentage of participants who are clinical disease activity-free at Months 36 and 48 [ Time Frame: Baseline and Months 36 and 48 ] [ Designated as safety issue: No ]
    Clinical disease activity-free is defined as no sustained EDSS progression and no relapses at Month 36 and 48. Sustained disability progression defined by at least a 1.0-point increase on the Expanded Disability Status Scale (EDSS) from a Baseline EDSS ≥1.0 that is sustained for 12 weeks, or at least a 1.5-point increase on the EDSS from a Baseline EDSS <1.0 that is sustained for 12 weeks. The EDSS measures the disability status of people with multiple sclerosis on a scale that ranges from 0 to 10, with higher scores indicating more disability.


Secondary Outcome Measures:
  • Identification of baseline prognostic factors that predict overall disease-free status [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
  • Identification of yearly prognostic factors that predict overall disease-free status [ Time Frame: Month 12 and Month 24 ] [ Designated as safety issue: No ]
  • Clinical disease-free status [ Time Frame: Months 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
  • Identification of baseline prognostic factors that predict clinical disease-free status [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
  • Identification of yearly prognostic factors that predict clinical disease-free status [ Time Frame: Month 48 ] [ Designated as safety issue: No ]
  • Annualized Relapse Rate (ARR) [ Time Frame: Months 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Relapses are defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the Examining Neurologist. The ARR will be calculated by tabulating the total number of relapses experienced in the group divided by the number of days up to the end of study, and the ratio then multiplied by 365.

  • Percentage of participants with Sustained EDSS progression [ Time Frame: Baseline and Months 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Sustained disability progression defined by at least a 1.0-point increase on the Expanded Disability Status Scale (EDSS) from a Baseline EDSS ≥1.0 that is sustained for 12 weeks, or at least a 1.5-point increase on the EDSS from a Baseline EDSS <1.0 that is sustained for 12 weeks. The EDSS measures the disability status of people with multiple sclerosis on a scale that ranges from 0 to 10, with higher scores indicating more disability.

  • Sustained EDSS improvement [ Time Frame: Baseline and Months 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Sustained improvement in disability is defined as participants with Baseline EDSS of at least 2.0 who experience a ≥1.0 decrease in EDSS that is sustained for 24 weeks.

  • Change form Baseline in number of new or newly enlarging T2 hyperintense lesions [ Time Frame: Baseline and Months 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Assessed by magnetic resonance imaging (MRI)

  • Change from Baseline in number of new T1 hypointense lesions [ Time Frame: Baseline and Months 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Assessed by magnetic resonance imaging (MRI)

  • Change form Baseline in number of Gadolinium (Gd)-enhancing lesions [ Time Frame: Baseline and Months 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Assessed by magnetic resonance imaging (MRI)

  • MRI brain atrophy measure [ Time Frame: Baseline and Months 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    Assessed by magnetic resonance imaging (MRI)

  • Change from Baseline in Retinal nerve fiber layer thickness [ Time Frame: Baseline and Month 12 and Month 48 ] [ Designated as safety issue: No ]
    Retinal nerve fiber layer thickness will be measured by Optical Coherence Tomography (OCT).

  • Change from Baseline in Low Contrast Visual Acuity [ Time Frame: Baseline and Month 12 and Month 48 ] [ Designated as safety issue: No ]
    Low-contrast visual acuity testing captures the minimum size at which individuals can perceive letters of a particular contrast level (shade of gray on white background). Using the low-contrast Sloan letter charts at 2.5% and 1.25% low contrast levels, participants will be asked to read each of the 2 charts at a 2-meter distance using a standardized testing protocol.

  • Change from Baseline in the Symbol Digit Modalities Test (SDMT) [ Time Frame: Baseline and Months 12, 24, 36 and 48 ] [ Designated as safety issue: No ]
    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).

  • Change from Baseline in Work Productivity and Activity Impairment (WPAI) questionnaire [ Time Frame: Baseline and Months 12, 24, 36 and 48 ] [ Designated as safety issue: No ]
    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. Presenteeism (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.

  • Quality of Life as measured by the Multiple Sclerosis Impact Scale (MSIS-29) [ Time Frame: Baseline and Months 12, 24, 36 and 48 ] [ Designated as safety issue: No ]
    The 29-item Multiple Sclerosis Impact Scale (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.


Estimated Enrollment: 300
Study Start Date: January 2012
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Study patients will be recruited by participating neurologists from among their MS patients who opt to begin treatment with Tysabri®.

Criteria

Key Inclusion Criteria:

  • 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 patient privacy regulations.
  • Documented diagnosis of Relapsing Multiple Sclerosis (McDonald 2010 Criteria ).
  • <3 year disease duration.
  • Must have an Expanded Disability Status Scale (EDSS) score from 0 to 4.0, inclusive.
  • Anti-JCV antibody negative test at Screening Visit
  • Must satisfy the approved therapeutic indications for Tysabri®.
  • Must be treatment-naïve to disease-modifying therapy (DMT) or have been treated with a single DMT (including Avonex, Betaseron, Rebif, Copaxone, Extavia, or Gilenya) for ≤12 months total prior to date of informed consent.
  • Decision to treat with Tysabri® must precede enrollment.

Key Exclusion Criteria:

  • Any prior treatment with Tysabri®.
  • Anti-JCV antibody positive at any timepoint prior to the Screening Visit.
  • Contraindications to treatment with Tysabri® as described in the US Prescribing Information.
  • History of progressive multifocal leukoencephalopathy (PML) or other opportunistic infections, or an increased risk for such infections.
  • History of diagnosis of Primary Progressive Multiple Sclerosis (PPM) and/or Secondary Progressive Multiple Sclerosis (SPMS).
  • Receiving immunomodulatory or immunosuppressive therapy.
  • Prior history of immunosuppressive use (mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate, cladribine, rituximab).
  • Immunocompromised at the time of enrollment.
  • Known active malignancies (subjects with cutaneous basal cell carcinoma that has been completely excised prior to study entry remain eligible).
  • Women breastfeeding, pregnant, or planning to become pregnant; women who are not post-menopausal or surgically sterile who are unwilling to practice contraception.
  • Inability to comply with study requirements.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01485003

Contacts
Contact: Biogen Idec clinicaltrials@biogenidec.com

  Show 64 Study Locations
Sponsors and Collaborators
Biogen Idec
Investigators
Study Director: Medical Director Biogen Idec
  More Information

No publications provided

Responsible Party: Biogen Idec
ClinicalTrials.gov Identifier: NCT01485003     History of Changes
Other Study ID Numbers: 101MS407
Study First Received: December 1, 2011
Last Updated: September 19, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on September 22, 2014