Trial record 1 of 1 for:    NCT01485003
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Observational Study of Tysabri in Early Relapsing-Remitting Multiple Sclerosis in Anti-JC Virus Antibody Negative Participants (STRIVE)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Biogen
ClinicalTrials.gov Identifier:
NCT01485003
First received: December 1, 2011
Last updated: July 10, 2015
Last verified: July 2015
  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 secondary objectives are: To identify prognostic factors at Baseline that predict overall disease-free status at Month 12, and to assess if yearly overall disease-free response factors predict overall disease-free status at Month 24; To evaluate clinical disease-free status (relapse, Expanded Disability Status Scale [EDSS]) at each analysis time point of Months 12, 24, 36, and 48; To identify prognostic factors at Baseline that predict clinical disease-free status at Month 12, and to assess yearly clinical disease-free response factors that predict clinical disease-free status (relapse, EDSS) in subsequent years at Months 24, 36, and 48; To evaluate the impact of Tysabri at each analysis time point of Months 12, 24, 36, and 48 on the following: annualized relapse rate (ARR), sustained EDSS progression and improvement (24-week sustained); To evaluate the impact of Tysabri at each analysis time point of Months 12, 24, 36, and 48 on the following: magnetic resonance image (MRI) measures: T2, T1, T1 with Gadolinium (Gd), brain atrophy; To evaluate the impact of Tysabri at Month 24 and Month 48 on the following: optical coherence tomography (OCT), Low and High Contrast Visual Acuity Assessment; To evaluate the impact of Tysabri at each analysis time point of Months 12, 24, 36, and 48 on the following: cognitive impairment (Symbol Digit Modalities Test [SDMT]), capacity for work (Work Productivity and Activity Impairment Questionnaire [WPAI]), quality of life (QoL) (Multiple Sclerosis Impact Scale [MSIS-29])


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:

Primary Outcome Measures:
  • Proportion 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 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 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.

  • Proportion 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.


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 overall disease-free response 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 clinical disease-free response factors that predict clinical disease-free status [ Time Frame: Month 48 ] [ Designated as safety issue: No ]
  • Annualized Relapse Rate [ Time Frame: Months 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    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. 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 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 as assessed by MRI [ Time Frame: Baseline and Months 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
  • Change from baseline in number of new T1 hypointense lesions as assessed by MRI [ Time Frame: Baseline and Months 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
  • Change form baseline in number of T1 lesions with Gd-enhancing lesions as assessed by MRI [ Time Frame: Baseline and Months 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
  • MRI brain atrophy as assessed by MRI [ Time Frame: Baseline and Months 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
  • Change from baseline in retinal nerve fiber layer (RNFL) thickness as assessed by OCT [ Time Frame: Baseline and Month 24 and Month 48 ] [ Designated as safety issue: No ]
  • Change from baseline in low contrast visual acuity [ Time Frame: Baseline and Month 24 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 high contrast visual acuity [ Time Frame: Baseline and Month 24 and Month 48 ] [ Designated as safety issue: No ]
    High contrast acuity testing is important to help determine the smallest letters a person can read on a standardized visual acuity chart or on a card held 14 - 20 feet away. A visual acuity test is a routine part of an eye examination.

  • Cognitive impairment as assessed by change from baseline in 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).

  • Capacity for work as assessed by change from baseline in 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 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.


Enrollment: 229
Study Start Date: January 2012
Estimated Study Completion Date: November 2018
Estimated Primary Completion Date: November 2018 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

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

Criteria

Key Inclusion Criteria:

  • 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 within 6 months of Screening Visit.
  • Must satisfy the approved therapeutic indications for Tysabri.
  • Must be treatment-naïve to disease-modifying therapy (DMT) or have been treated with DMT (including but not limited to Avonex, Betaseron, Rebif, Copaxone, Extavia, or Gilenya) for ≤36 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

  Show 43 Study Locations
Sponsors and Collaborators
Biogen
Investigators
Study Director: Medical Director Biogen
  More Information

No publications provided

Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT01485003     History of Changes
Other Study ID Numbers: 101MS407
Study First Received: December 1, 2011
Last Updated: July 10, 2015
Health Authority: United States: Institutional Review Board

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

ClinicalTrials.gov processed this record on July 30, 2015