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A Prospective, Open-label, Non-randomized, Clinical Trial to Determine if Natalizumab (Tysabri®) Improves Ambulatory Measures in Relapsing-remitting Multiple Sclerosis (RRMS) Patients (TIMER)

This study has been completed.
Sponsor:
Collaborator:
Elan Pharmaceuticals
Information provided by (Responsible Party):
Biogen Idec
ClinicalTrials.gov Identifier:
NCT00871780
First received: March 26, 2009
Last updated: November 11, 2014
Last verified: November 2014
  Purpose

The primary objective of the study is to evaluate the evolution of walking capacity as measured by the timed 100-meter walk test (T100T), timed 25-foot walk test (T25FW), maximum walking distance (MWD), and Expanded Disability Status Scale (EDSS) during the first year of therapy with natalizumab. The secondary objectives of this study are as follows:

  • To evaluate the correlation between the MWD and EDSS and both walking tests, the T100T and the T25FW at Baseline, at Week 24 and at Week 48 of therapy.
  • To determine how well each of the walking tests, T100T or T25FW, predicts walking limitations in all participants and in the subgroups of participants stratified by baseline EDSS.

Condition Intervention Phase
Relapsing Remitting Multiple Sclerosis (RRMS)
Drug: BG00002 (natalizumab)
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Open-label, Non-randomized, Clinical Trial to Determine if Natalizumab (Tysabri®) Improves Ambulatory Measures in Relapsing-remitting Multiple Sclerosis (RRMS) Patients "TIMER" Study

Resource links provided by NLM:


Further study details as provided by Biogen Idec:

Primary Outcome Measures:
  • Change From Baseline in the Timed 100-meter Walk Test (T100T) [ Time Frame: Baseline, Week 24, Week 48 ] [ Designated as safety issue: No ]
    In the T100T, the participant is instructed to walk as fast as possible for a distance of 100 meters.

  • Change From Baseline in the Timed 25-foot Walk Test (T25FW) [ Time Frame: Baseline, Week 24, Week 48 ] [ Designated as safety issue: No ]
    In the T25FW, the participant is instructed to walk as fast as possible for a distance of 25 feet.

  • Change From Baseline in Maximum Walking Distance (MWD) [ Time Frame: Baseline, Week 24, Week 48 ] [ Designated as safety issue: No ]
  • Change From Baseline in Expanded Disability Status Scale (EDSS) [ Time Frame: Baseline, Week 24, Week 48 ] [ Designated as safety issue: No ]
    EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated.


Secondary Outcome Measures:
  • Correlation Between the EDSS and MWD (Pearson Correlation Coefficient) [ Time Frame: Baseline, Week 24, Week 48 ] [ Designated as safety issue: No ]
    Pearson correlation coefficient is a measure of the linear correlation (dependence) between 2 variables, giving a value between +1 and −1 inclusive, where 1 is total positive correlation, 0 is no correlation, and −1 is total negative correlation.

  • Correlation Between the EDSS and MWD (Spearman Correlation Coefficient) [ Time Frame: Baseline, Week 24, Week 48 ] [ Designated as safety issue: No ]
    Spearman correlation coefficient is a non-parametric measure of the correlation (dependence) between 2 variables, giving a value between +1 and −1 inclusive, where 1 is total positive correlation, 0 is no correlation, and −1 is total negative correlation.

  • Correlation Between the T100T and T25FW (Pearson Correlation Coefficient) [ Time Frame: Baseline, Week 24, Week 48 ] [ Designated as safety issue: No ]
    Pearson correlation coefficient is a measure of the linear correlation (dependence) between 2 variables, giving a value between +1 and −1 inclusive, where 1 is total positive correlation, 0 is no correlation, and −1 is total negative correlation.

  • Correlation Between the T100T and T25FW (Spearman Correlation Coefficient) [ Time Frame: Baseline, Week 24, Week 48 ] [ Designated as safety issue: No ]
    Spearman correlation coefficient is a non-parametric measure of the correlation (dependence) between 2 variables, giving a value between +1 and −1 inclusive, where 1 is total positive correlation, 0 is no correlation, and −1 is total negative correlation.

  • Correlation Between the EDSS and T25FW (Pearson Correlation Coefficient) [ Time Frame: Baseline, Week 24, Week 48 ] [ Designated as safety issue: No ]
    Pearson correlation coefficient is a measure of the linear correlation (dependence) between 2 variables, giving a value between +1 and −1 inclusive, where 1 is total positive correlation, 0 is no correlation, and −1 is total negative correlation.

  • Correlation Between the EDSS and T25FW (Spearman Correlation Coefficient) [ Time Frame: Baseline, Week 24, Week 48 ] [ Designated as safety issue: No ]
    Spearman correlation coefficient is a non-parametric measure of the correlation (dependence) between 2 variables, giving a value between +1 and −1 inclusive, where 1 is total positive correlation, 0 is no correlation, and −1 is total negative correlation.

  • Correlation Between the EDSS and T100T (Pearson Correlation Coefficient) [ Time Frame: Baseline, Week 24, Week 48 ] [ Designated as safety issue: No ]
    Pearson correlation coefficient is a measure of the linear correlation (dependence) between 2 variables, giving a value between +1 and −1 inclusive, where 1 is total positive correlation, 0 is no correlation, and −1 is total negative correlation.

  • Correlation Between the EDSS and T100T (Spearman Correlation Coefficient) [ Time Frame: Baseline, Week 24, Week 48 ] [ Designated as safety issue: No ]
    Spearman correlation coefficient is a non-parametric measure of the correlation (dependence) between 2 variables, giving a value between +1 and −1 inclusive, where 1 is total positive correlation, 0 is no correlation, and −1 is total negative correlation.

  • Improvement in Timed 25FT Walk Speed and T100T Speed at Week 24 and 48 [ Time Frame: Baseline, Week 24, Week 48 ] [ Designated as safety issue: No ]
    To determine how well each of the walking tests, T100T or T25FW, predicts walking limitations, participants were stratified by baseline EDSS scores, and walking tests at Weeks 24 and 48 were analyzed. A 15% or 20% improvement indicates that, when compared with baseline walking speed (meters per second), there is at least 15% or 20% improvement at the corresponding timepoint, e.g. (speed at Week 24 - speed at baseline)/speed at baseline*100% ≥ 15% or 20%. Confirmed (conf) improvement at Week 48 indicates that the participant has at least 15% (or 20%) improvement in walking speed at both Week 24 and Week 48.


Enrollment: 224
Study Start Date: August 2009
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Natalizumab
natalizumab 300 mg IV every 4 weeks for 48 weeks
Drug: BG00002 (natalizumab)
Other Name: Tysabri®

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Must give written informed consent and provide all authorizations required by local law (for example, Protected Health Information [PHI])
  • Men or women between 18 and 60 years of age, inclusive
  • Must have Expanded Disability Status Scale (EDSS) less than or equal to 5.5 at baseline
  • Must be able to walk at least 100 m without assistive devices
  • Must be natalizumab-naïve
  • Must have a documented diagnosis of a relapsing remitting form of multiple sclerosis (MS0 as defined by the revised McDonald Committee criteria (Polman et al., 2005)
  • Must have had a recent (within 3 months from baseline) magnetic resonance imaging (MRI)
  • Must have had at least 1 relapse in the previous year and must satisfy the locally approved therapeutic indications for Tysabri. If Tysabri is not yet approved in a specific country, patients must fulfill the following criteria:

    • Patients with high disease activity despite treatment with a beta-interferon defined as patients who have failed to respond to a full and adequate course of a beta-interferon
    • Patients must have had at least 1 relapse in the previous year while on therapy, and have at least 9 T2 hyperintense lesions in cranial MRI or at least 1 gadolinium (Gd)-enhancing lesion
    • Patients with rapidly evolving severe relapsing remitting multiple sclerosis defined as patients who have had 2 or more disabling relapses in one year and 1 or more Gd-enhancing lesions on brain MRI or significant increase in T2 lesions as compared to a previous MRI
  • Must be stable in disability for at least 30 days prior to enrollment to the study
  • Must be stable in symptomatic management of the disease, specifically spasticity, depression and fatigue for at least 30 days prior to enrollment to the study
  • Must be considered by the Investigator to be free of signs and symptoms suggestive of progressive multifocal leukoencephalopathy (PML) based on medical history, physical examination, or laboratory testing
  • Must be willing to discontinue and remain free from concomitant immunosuppressive or immunomodulatory treatment (including interferon [IFN] and glatiramer acetate [GA]) while being treated with natalizumab during the study.

Key Exclusion Criteria:

Unless otherwise specified, candidates will be excluded from study entry if any of the following exclusion criteria exist at the time of the Screening Visit:

  • Onset of a relapse within 50 days prior to first infusion
  • Considered by the Investigator to be immunocompromised, based on medical history, physical examination, or laboratory testing or due to prior immunosuppressive treatment
  • History of, or available abnormal laboratory results indicative of, any significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric (including major depression), renal, and/or other major disease that would preclude the administration of a recombinant humanized antibody immunomodulating agent. The Investigator must re-review the subject's medical fitness for participation and consider any diseases that would preclude treatment
  • History of malignancy (subjects with basal cell carcinoma that has been completely excised prior to study entry remain eligible)
  • Known history of human immunodeficiency virus infection or hematological malignancy
  • History of organ transplantation (including anti-rejection therapy)
  • A clinically significant infectious illness (cellulitis, abscess, pneumonia, septicemia) within 30 days prior to the Screening Visit
  • Treatment with immunosuppressant medications (mitoxantrone, cyclophosphamide, cyclosporine, azathioprine, methotrexate) within 6 months prior to Screening
  • Female subjects who are not postmenopausal for at least 1 year, surgically sterile (does not include tubal ligation), or willing to practice effective contraception (as defined by the Investigator) during the study
  • Women who are breastfeeding, pregnant, or planning to become pregnant while on study
  • Current enrollment in any other study treatment or disease study
  • Unwillingness or inability to comply with the requirements of this protocol, including the presence of any condition (physical, mental, or social) that is likely to affect the subject's ability to comply with the study protocol
  • Subjects with walking impairment due to causes other than MS
  • Other unspecified reasons that, in the opinion of the Investigator and/or Biogen Idec, make the subject unsuitable for enrollment into this study

NOTE: Other eligibility 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: NCT00871780

Locations
Belgium
Biogen Idec Investigative Site
Liege, Belgium
Mexico
Biogen Idec Investigative Site
Puebla, Mexico
Poland
Biogen Idec Investigative Site
Bialystok, Poland
Biogen Idec Investigative Site
Bydgoszcz, Poland
Biogen Idec Investigative Site
Lotz, Poland
Biogen Idec Investigative Site
Poznan, Poland
Biogen Idec Investigative Site
Warszawa, Poland
Romania
Biogen Idec Investigative Site
Bucharest, Romania
Biogen Idec Investigative Site
Mures, Romania
Saudi Arabia
Biogen Idec Investigative Site
Riyadh, Saudi Arabia
Ukraine
Biogen Idec Investigative Site
Dnipropetrovsk, Ukraine
Biogen Idec Investigative Site
Kharkiv, Ukraine
Biogen Idec Investigative Site
Kyiv, Ukraine
Biogen Idec Investigative Site
Lviv, Ukraine
Biogen Idec Investigative Site
Simferopol, Ukraine
Sponsors and Collaborators
Biogen Idec
Elan Pharmaceuticals
Investigators
Study Director: Medical Director Biogen Idec
  More Information

No publications provided

Responsible Party: Biogen Idec
ClinicalTrials.gov Identifier: NCT00871780     History of Changes
Other Study ID Numbers: TYS-IMA-08-11
Study First Received: March 26, 2009
Results First Received: November 11, 2014
Last Updated: November 11, 2014
Health Authority: Romania: National Authority for Scientific Research
Belgium: Federal Agency for Medicinal Products and Health Products
Romania: National Medicines Agency
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
Mexico: National Institute of Public Health, Health Secretariat
Romania: Ministry of Public Health
Mexico: Federal Commission for Protection Against Health Risks
Mexico: National Council of Science and Technology
Saudi Arabia: Research Advisory Council
Mexico: Federal Commission for Sanitary Risks Protection
Poland: Ministry of Health
Belgium: Ministry of Social Affairs, Public Health and the Environment
Saudi Arabia: Ministry of Health
Mexico: Ethics Committee
Belgium: Institutional Review Board
Romania: State Institute for Drug Control
Mexico: Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Poland: Ministry of Science and Higher Education
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Ukraine: Ministry of Health
Ukraine: State Pharmacological Center - Ministry of Health

Keywords provided by Biogen Idec:
TYSABRI naive
Relapsing-remitting multiple sclerosis (RRMS)

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 November 25, 2014