Relapsing Remitting Multiple Sclerosis (RRMS)Phase 4TIMERNCT00871780
A Prospective, Open-label, Non-randomized, Clinical Trial to Determine if Natalizumab (Tysabri®) Improves Ambulatory Measures in Relapsing-remitting Multiple Sclerosis (RRMS) Patients
A Phase 4 study testing BG00002 (natalizumab) in people with Relapsing Remitting Multiple Sclerosis (RRMS), run by Biogen at 15 sites in 6 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Relapsing Remitting Multiple Sclerosis (RRMS)
- What is being tested?
- BG00002 (natalizumab)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 224 participants
- Where
- 15 sitesin 6 countries
- Study dates
- Aug 2009to Jul 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
15 sites in 6 countries.
15 sites in 6 countries
Poland5 sites
Biogen Idec Investigative Site
Bialystok
Biogen Idec Investigative Site
Bydgoszcz
Biogen Idec Investigative Site
Lodz
Biogen Idec Investigative Site
Poznan
Biogen Idec Investigative Site
Warsaw
Ukraine5 sites
Biogen Idec Investigative Site
Dnipropetrovsk
Biogen Idec Investigative Site
Kharkiv
Biogen Idec Investigative Site
Kyiv
Biogen Idec Investigative Site
Lviv
Biogen Idec Investigative Site
Simferopol
Romania2 sites
Biogen Idec Investigative Site
Bucharest
Biogen Idec Investigative Site
Mures
About this study
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
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.
- Being tested
- BG00002 (natalizumab)
- Keywords
- TYSABRI naive, Relapsing-remitting multiple sclerosis (RRMS)
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BG00002 (natalizumab)Drug
Also called Tysabri®
| Study group | Role | What they receive |
|---|---|---|
| Natalizumab | Experimental | natalizumab 300 mg IV every 4 weeks for 48 weeks Receives: Drug: BG00002 (natalizumab) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in the Timed 100-meter Walk Test (T100T)
In the T100T, the participant is instructed to walk as fast as possible for a distance of 100 meters.
Measured: Baseline, Week 24, Week 48
Change From Baseline in the Timed 25-foot Walk Test (T25FW)
In the T25FW, the participant is instructed to walk as fast as possible for a distance of 25 feet.
Measured: Baseline, Week 24, Week 48
Change From Baseline in Maximum Walking Distance (MWD)
Measured: Baseline, Week 24, Week 48
Change From Baseline in Expanded Disability Status Scale (EDSS)
EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated.
Measured: Baseline, Week 24, Week 48
Secondary outcomes (9)
Correlation Between the EDSS and MWD (Pearson Correlation Coefficient)
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.
Measured: Baseline, Week 24, Week 48
Correlation Between the EDSS and MWD (Spearman Correlation Coefficient)
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.
Measured: Baseline, Week 24, Week 48
Correlation Between the T100T and T25FW (Pearson Correlation Coefficient)
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.
Measured: Baseline, Week 24, Week 48
Correlation Between the T100T and T25FW (Spearman Correlation Coefficient)
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.
Measured: Baseline, Week 24, Week 48
Correlation Between the EDSS and T25FW (Pearson Correlation Coefficient)
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.
Measured: Baseline, Week 24, Week 48
Correlation Between the EDSS and T25FW (Spearman Correlation Coefficient)
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.
Measured: Baseline, Week 24, Week 48
Correlation Between the EDSS and T100T (Pearson Correlation Coefficient)
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.
Measured: Baseline, Week 24, Week 48
Correlation Between the EDSS and T100T (Spearman Correlation Coefficient)
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.
Measured: Baseline, Week 24, Week 48
Improvement in Timed 25FT Walk Speed and T100T Speed at Week 24 and 48
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.
Measured: Baseline, Week 24, Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2009 (estimated)
- Study startAug 2009
- Primary completionJul 2012
- Study completionJul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Relapsing Remitting Multiple Sclerosis (RRMS)Studies of the same condition, open and under way.
- More trials run by BiogenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 224 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Elan Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Biogen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00871780
- Sponsor's protocol ID
- TYS-IMA-08-11
- Acronym
- TIMER
- Status last verified
- Feb 2017
- First submitted
- 26 Mar 2009
- Last updated
- 21 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Voloshyna N, Havrdova E, Hutchinson M, Nehrych T, You X, Belachew S, Hotermans C, Paes D. Natalizumab improves ambulation in relapsing-remitting multiple sclerosis: results from the prospective TIMER study and a retrospective analysis of AFFIRM. Eur J Neurol. 2015 Mar;22(3):570-7. doi: 10.1111/ene.12618. Epub 2014 Dec 15.
PubMed 25511792
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00871780
- Acronym / sponsor ID
- TIMER / TYS-IMA-08-11
- Keywords
- TYSABRI naive, Relapsing-remitting multiple sclerosis (RRMS)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 224 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Collaborators
- Elan Pharmaceuticals
- Study start
- Aug 2009
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 30 Mar 2009 (estimated)
- Results
- Posted 18 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Natalizumab | Experimental | Drug: BG00002 (natalizumab)natalizumab 300 mg IV every 4 weeks for 48 weeks |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (16 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BG00002 (natalizumab)Also: Tysabri® | Drug | Natalizumab |
Primary outcome
Change From Baseline in the Timed 100-meter Walk Test (T100T)
Time frame: Baseline, Week 24, Week 48
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
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
Change From Baseline in Expanded Disability Status Scale (EDSS)
Time frame: Baseline, Week 24, Week 48
EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated.
9 secondary outcomes
Correlation Between the EDSS and MWD (Pearson Correlation Coefficient)
Time frame: Baseline, Week 24, Week 48
Correlation Between the EDSS and MWD (Spearman Correlation Coefficient)
Time frame: Baseline, Week 24, Week 48
Correlation Between the T100T and T25FW (Pearson Correlation Coefficient)
Time frame: Baseline, Week 24, Week 48
Correlation Between the T100T and T25FW (Spearman Correlation Coefficient)
Time frame: Baseline, Week 24, Week 48
Correlation Between the EDSS and T25FW (Pearson Correlation Coefficient)
Time frame: Baseline, Week 24, Week 48
Correlation Between the EDSS and T25FW (Spearman Correlation Coefficient)
Time frame: Baseline, Week 24, Week 48
Correlation Between the EDSS and T100T (Pearson Correlation Coefficient)
Time frame: Baseline, Week 24, Week 48
Correlation Between the EDSS and T100T (Spearman Correlation Coefficient)
Time frame: Baseline, Week 24, Week 48
Improvement in Timed 25FT Walk Speed and T100T Speed at Week 24 and 48
Time frame: Baseline, Week 24, Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25511792Voloshyna N, Havrdova E, Hutchinson M, Nehrych T, You X, Belachew S, Hotermans C, Paes D. Natalizumab improves ambulation in relapsing-remitting multiple sclerosis: results from the prospective TIMER study and a retrospective analysis of AFFIRM. Eur J Neurol. 2015 Mar;22(3):570-7. doi: 10.1111/ene.12618. Epub 2014 Dec 15.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Biogen
15 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing BG00002 (natalizumab) in people with Relapsing Remitting Multiple Sclerosis (RRMS), run by Biogen at 15 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Poland, Ukraine, Romania, Belgium, Mexico and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in the Timed 100-meter Walk Test (T100T) (time frame: Baseline, Week 24, Week 48). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00871780, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2017.