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

This study has been completed.
Sponsor:
Collaborator:
Elan Pharmaceuticals
Information provided by:
Biogen Idec
ClinicalTrials.gov Identifier:
NCT00871780
First received: March 26, 2009
Last updated: September 12, 2013
Last verified: August 2012
  Purpose

The aim of this study is to evaluate the evolution of walking capacity as measured by T100T, T25FW, MWD and EDSS during the first year of therapy with natalizumab.


Condition Intervention Phase
Relapsing Remitting Multiple Sclerosis (RRMS)
Drug: Natalizumab (Tysabri®)
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
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:
  • The primary objective of the study is to evaluate the evolution of walking capacity as measured by T100T, T25FW, MWD, and EDSS during the first year of therapy with natalizumab. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the correlation between the MWD and EDSS and both walking tests, the T100T and the T25FW at baseline, at 6 months and at 1 year of therapy. Also, how the walking tests predicts limitations in all subjects and in the subgroups of subjects. [ Time Frame: 6 months and 1 year ] [ Designated as safety issue: No ]

Enrollment: 200
Study Start Date: August 2009
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Natalizumab (Tysabri®)
    Single arm. Eligible subjects will receive natalizumab 300 mg IV every 4 weeks for 48 weeks.
Detailed Description:

Maximum walking distance (MWD) without aid or rest is important in daily life of multiple sclerosis (MS) patients. In practice, it is difficult to measure MWD and the anamnesis poorly matches the reality. A new easy-to-use sensitive tool, the Timed 100-meter walk test (T100T) has been shown to be superior to the Timed 25-Foot walk (T25FW) in terms of discriminatory power for the detection and evaluation of restricted walking capacities in MS patients (Belachew et al.,2008). The T100T could be of interest for clinical trials studying disability worsening and improvement across the spectrum of EDSS. It may provide a more sensitive measure for ambulation changes in quantifying progressive MS pathology.

  Eligibility

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

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 EDSS less than or equal to 5.5 at baseline.
  • Must be able to walk at least 100m without assistive devices
  • Must be natalizumab naïve.
  • Must have a documented diagnosis of a relapsing remitting form of MS as defined by the revised McDonald Committee criteria (Polman et al., 2005)
  • Must have had a recent MRI (within 3 months from baseline).
  • 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 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 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 IFN and GA) while being treated with natalizumab during the study.

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00871780

Locations
Belgium
Biogen Idec Investigative Site
Liege, Belgium, B-4000
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, 11461
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
  More Information

No publications provided

Responsible Party: Regine Buffels, MD, Biogen Idec
ClinicalTrials.gov Identifier: NCT00871780     History of Changes
Other Study ID Numbers: TYS-IMA-08-11
Study First Received: March 26, 2009
Last Updated: September 12, 2013
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

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

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 April 15, 2014