Multiple Sclerosis, Relapsing-RemittingPhase 3NCT00027300
Safety and Efficacy of Natalizumab in the Treatment of Multiple Sclerosis
A Phase 3 study testing Natalizumab in people with Multiple Sclerosis, Relapsing-Remitting, run by Biogen at 53 sites in 8 countries.
Trial summary
The purpose of this study is to determine the safety and efficacy of natalizumab in the treatment of individuals who have been diagnosed with relapsing remitting multiple sclerosis (MS). Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting
- What is being tested?
- Natalizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 900 participants
- Where
- 53 sitesin 8 countries
- Study dates
- Nov 2001to Jan 2005
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Diagnosis of MS, as defined by McDonald et al., criteria # 1-4 (McDonald et al., 2001)
- Between the ages of 18 and 50, inclusive.
- Baseline EDSS score between 0.0 and 5.0, inclusive.
- Have experienced at least one relapse within the 12 months prior to randomization.
- Cranial MRI scan demonstrating lesion(s) consistent with MS.
- Have given written informed consent to participate in the study.
Who cannot join
- Primary progressive, secondary progressive, or progressive relapsing MS.
- MS relapse has occurred,in the opinion of the investigator, within 50 days prior to randomization and/or the subject has not stabilized from a previous relapse.
- A clinically significant infectious illness within 30 days prior to randomization.
- History of, or abnormal laboratory results indicative of any significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric, renal and/or other major disease, that in the opinion of the investigator, would preclude the administration of a recombinant humanized antibody immunomodulating agent for 116 weeks.
- History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
- Unable to perform the Timed 25-foot Walk, 9HPT, and PASAT 3.
- Abnormal blood tests performed at the Screening Visit.
Trial locations and contacts
53 sites in 8 countries.
53 sites in 8 countries
United States14 sites
CMRRC
Albuquerque, New Mexico, 87131
Lehigh Valley Hospital, Neurosciences Research
Allentown, Pennsylvania, 18103
East Bay Region Associates in Neurology
Berkeley, California, 94705
Texas Neurology
Dallas, Texas, 75214
UC Davis School of Medicine, Department of Neurology
Davis, California, 95817-2307
Michigan Institute for Neurological Disorders
Farmington Hills, Michigan, 48335
University of Kansas Medical Center, Department of Neurology
Kansas City, Kansas, 66160
University of Miami School of Medicine, Department of Neurology
Miami, Florida, 33136
Yale University School of Medicine, Department of Neurology
New Haven, Connecticut, 06510
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Oregon Health Sciences University, Department of Neurology
Portland, Oregon, 97201-3098
Mayo Clinic Scottsdale
Scottsdale, Arizona, 85259
University of Washington MS Research Center
Seattle, Washington, 98195
Gimbel MS Center
Teaneck, New Jersey, 07666
United Kingdom13 sites
Oldchurch Hospital
Essex, NE1 4LP
Ipswich Hospital NHS Trust - Department of Clinical Neurology
Ipswich, IP4 5PD
St. James University Hospital, Department of Neurology
Leeds, LS9 7TF
Guy's Hospital
London, SE1 9RT
King's College Hospital
London, SE5 9RS
Kings College Hospital, Kings Neuroscience Center
London, SE5 9RS
Royal Victoria Infirmary
Newcastle upon Tyne, NE1 4LP
The Radcliffe Infirmary, University Department of Clinical Neurology
Oxford, OX2 0HE
Institute of Neurology
Queen Square, London, WC1N 3BG
Royal Hallamshire Hospital
Sheffield, S10 2JF
North Staffordshire Royal Infirmary - Neurology Department
Stoke-on-Trent, ST4 7LN
The Royal London Hospital
Whitechapel, London, E1 1BB
Atkin's Morely Hospital
Wimbledon, London, SW20 0NE
Canada9 sites
MS Research Unit, Center for Clinical Research
Halifax, B3H 1V7
Kingston General Hospital, Neurology
Kingston, Ontario, K7L 2V7
University Hospital
London, Ontario, N6A 5A5
Family Medical Centre
Ottawa, K1N 5C7
CHVO Hull Hospital
Québec, Quebec, J8Y 1W7
Sunnybrook and Women's College and Health Science Centre
Toronto, Ontario, M4N 3M5
University of Toronto, MS Clinic, St. Michael's Hospital
Toronto, Ontario, M5B 1W8
Vancouver Hospital and Health Sciences Center UBC Pavilion, MS Clinical Research Group
Vancouver, British Columbia, V6T 2B5
Health Services Centre
Winnipeg, Manitoba, R3A 1R9
Czechia9 sites
Faculty Hospital Brno Bohunice
Brno, 60200
Faculty Hospital St. Anne
Brno, 656 91
Faculty Hospital of Hradec Kralove
Hradec Králové, 500 05
Faculty Hospital Olomouc
Olomouc, 775 20
Faculty Hospital Of Ostrava Poruba
Ostrava, 70852
Hospital Pardubice - Department of Neurology
Pardubice, 532 03
Faculty Hospital Plzen - Clinic of Neurology
Pilsen, 304 60
General Teaching Hospital - Neurological Department
Prague, 2 12802
Faculty Hospital Motol - Neurological Clinic
Prague, 5 105 06
Belgium3 sites
Algemeen Ziekenhuis St. Jan
Bruges, 8000
LUC- University Centre
Diepenbeek, 3590
National MS Centrum
Melsbroek, 1820
France2 sites
Hopital de la Timone, Service de Neurologie
Marseille, 13385
CHRU - Hopital de Pontchaillou, Service de Neurologie
Rennes, 35033
Germany2 sites
St. Josef-Hospital, Neurologische Klinik der Ruhruniversitat Bochum
Bochurn, 44791
Klinika Neurologii
Bydgoszcz, 85-681
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Determine the Safety and Efficacy of Natalizumab in Subjects With Relapsing-Remitting Multiple Sclerosis
The purpose of this study is to determine the safety and efficacy of natalizumab in the treatment of individuals who have been diagnosed with relapsing remitting multiple sclerosis (MS). It is hoped that natalizumab will prevent certain types of white blood cells from moving out of the bloodstream into organs, including the brain, that are being damaged by autoimmune disease (a disease in which the body's own immune system attacks certain organs). These white blood cells are thought to cause inflammation that can result in lesions (small areas of damage) in the brain. These lesions are thought to be the cause of relapses and disability in MS.
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Being tested
- Natalizumab, Placebo
- Keywords
- Relapsing Remitting Multiple Sclerosis
- 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.
NatalizumabDrug
Also called Tysabri
Natalizumab 300 mg IV infusion, every 4 weeks, for up to 116 weeks.
PlaceboDrug
Placebo, IV infusion, every 4 weeks, for up to 116 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Natalizumab 300 mg, IV Receives: Drug: Natalizumab |
| Group 2 | Placebo comparator | Placebo IV infusion Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary objectives of this study are to determine whether natalizumab, when compared with placebo, is effective in reducing the rate of clinical relapses at 1 year and, in slowing the progression of disability at 2 years.
Measured: 1 year and 2 years
Secondary outcomes (1)
Reduction in MRI changes and clinical relapses
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2001 (estimated)
- Study startNov 2001
- Primary completionNov 2004
- Study completionJan 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Multiple Sclerosis, Relapsing-RemittingStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 900 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Elan Pharmaceuticals
- Investigators
- Michael Panzara, MD, MPH, Study director, BiogenChris Polman, MD, Principal investigator, VU Medical Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00027300
- Sponsor's protocol ID
- C-1801
- Status last verified
- Jan 2017
- First submitted
- 30 Nov 2001
- Last updated
- 9 Jan 2017
- Results posted
- No
- Data monitoring committee
- Yes
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 25511792Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW; AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006 Mar 2;354(9):899-910. doi: 10.1056/NEJMoa044397.
PubMed 16510744Nakamura K, Sun Z, Hara-Cleaver C, Bodhinathan K, Avila RL. Natalizumab reduces loss of gray matter and thalamic volume in patients with relapsing-remitting multiple sclerosis: A post hoc analysis from the randomized, placebo-controlled AFFIRM trial. Mult Scler. 2024 May;30(6):687-695. doi: 10.1177/13524585241235055. Epub 2024 Mar 12.
PubMed 38469809Strijbis EM, Coerver E, Mostert J, van Kempen ZLE, Killestein J, Comtois J, Repovic P, Bowen JD, Cutter G, Koch M. Association of age and inflammatory disease activity in the pivotal natalizumab clinical trials in relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry. 2023 Oct;94(10):792-799. doi: 10.1136/jnnp-2022-330887. Epub 2023 May 12.
PubMed 37173129Balcer LJ, Galetta SL, Polman CH, Eggenberger E, Calabresi PA, Zhang A, Scanlon JV, Hyde R. Low-contrast acuity measures visual improvement in phase 3 trial of natalizumab in relapsing MS. J Neurol Sci. 2012 Jul 15;318(1-2):119-24. doi: 10.1016/j.jns.2012.03.009. Epub 2012 Apr 21.
PubMed 22521274
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Determine the Safety and Efficacy of Natalizumab in Subjects With Relapsing-Remitting Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT00027300
- Acronym / sponsor ID
- C-1801
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Keywords
- Relapsing Remitting Multiple Sclerosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 900 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Collaborators
- Elan Pharmaceuticals
- Study start
- Nov 2001
- Primary completion
- Nov 2004 (actual)
- Study completion
- Jan 2005 (actual)
- First posted
- 3 Dec 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the safety and efficacy of natalizumab in the treatment of individuals who have been diagnosed with relapsing remitting multiple sclerosis (MS). It is hoped that natalizumab will prevent certain types of white blood cells from moving out of the bloodstream into organs, including the brain, that are being damaged by autoimmune disease (a disease in which the body's own immune system attacks certain organs). These white blood cells are thought to cause inflammation that can result in lesions (small areas of damage) in the brain. These lesions are thought to be the cause of relapses and disability in MS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: NatalizumabNatalizumab 300 mg, IV |
| Group 2 | Placebo comparator | Drug: PlaceboPlacebo IV infusion |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Diagnosis of MS, as defined by McDonald et al., criteria # 1-4 (McDonald et al., 2001)
- Between the ages of 18 and 50, inclusive.
- Baseline EDSS score between 0.0 and 5.0, inclusive.
- Have experienced at least one relapse within the 12 months prior to randomization.
- Cranial MRI scan demonstrating lesion(s) consistent with MS.
Key exclusion criteria (7 listed)
- Primary progressive, secondary progressive, or progressive relapsing MS.
- MS relapse has occurred,in the opinion of the investigator, within 50 days prior to randomization and/or the subject has not stabilized from a previous relapse.
- A clinically significant infectious illness within 30 days prior to randomization.
- History of, or abnormal laboratory results indicative of any significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric, renal and/or other major disease, that in the opinion of the investigator, would preclude the administration of a recombinant humanized antibody immunomodulating agent for 116 weeks.
- History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
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 |
|---|---|---|
| NatalizumabAlso: TysabriNatalizumab 300 mg IV infusion, every 4 weeks, for up to 116 weeks. | Drug | Group 1 |
| PlaceboPlacebo, IV infusion, every 4 weeks, for up to 116 weeks. | Drug | Group 2 |
Primary outcome
The primary objectives of this study are to determine whether natalizumab, when compared with placebo, is effective in reducing the rate of clinical relapses at 1 year and, in slowing the progression of disability at 2 years.
Time frame: 1 year and 2 years
1 secondary outcome
Reduction in MRI changes and clinical relapses
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2017.
- 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.
- Results publication: PubMed 16510744Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW; AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006 Mar 2;354(9):899-910. doi: 10.1056/NEJMoa044397.
- Derived from this study: PubMed 38469809Nakamura K, Sun Z, Hara-Cleaver C, Bodhinathan K, Avila RL. Natalizumab reduces loss of gray matter and thalamic volume in patients with relapsing-remitting multiple sclerosis: A post hoc analysis from the randomized, placebo-controlled AFFIRM trial. Mult Scler. 2024 May;30(6):687-695. doi: 10.1177/13524585241235055. Epub 2024 Mar 12.
- Derived from this study: PubMed 37173129Strijbis EM, Coerver E, Mostert J, van Kempen ZLE, Killestein J, Comtois J, Repovic P, Bowen JD, Cutter G, Koch M. Association of age and inflammatory disease activity in the pivotal natalizumab clinical trials in relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry. 2023 Oct;94(10):792-799. doi: 10.1136/jnnp-2022-330887. Epub 2023 May 12.
- Derived from this study: PubMed 22521274Balcer LJ, Galetta SL, Polman CH, Eggenberger E, Calabresi PA, Zhang A, Scanlon JV, Hyde R. Low-contrast acuity measures visual improvement in phase 3 trial of natalizumab in relapsing MS. J Neurol Sci. 2012 Jul 15;318(1-2):119-24. doi: 10.1016/j.jns.2012.03.009. Epub 2012 Apr 21.
- The web site of the National Multiple Sclerosis Society, an organization dedicated to providing information to individuals with MS, their families and healthcare providersLink provided by the sponsor.
- MSActiveSource.com is a resource for news, information and disease management for all individuals touched by multiple sclerosis. This site is sponsored by Biogen.Link provided by the sponsor.
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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.
Michael Panzara, MD, MPH study director
Biogen
Chris Polman, MD principal investigator
VU Medical Centre
53 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Natalizumab in people with Multiple Sclerosis, Relapsing-Remitting, run by Biogen at 53 sites in 8 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 6 inclusion and 7 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 9 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 53 sites in United States, United Kingdom, Canada, Czechia, Belgium and 3 more countries. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The primary objectives of this study are to determine whether natalizumab, when compared with placebo, is effective in reducing the rate of clinical relapses at 1 year and, in slowing the progression of disability at 2 years. (time frame: 1 year and 2 years). 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 NCT00027300, which also lists 5 linked publications.
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 9 Jan 2017.