Relapsing Remitting Multiple SclerosisPhase 2RESTORENCT01071083

Treatment Interruption of Natalizumab

A Phase 2 study testing natalizumab, interferon beta 1-a and methylprednisolone in people with Relapsing Remitting Multiple Sclerosis, run by Biogen at 33 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a randomized, rater blinded trial in patients who interrupt treatment with natalizumab with or without being treated with other immunomodulatory drugs, or continue treatment 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
What is being tested?: natalizumab, interferon beta 1-a and methylprednisolone
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 175 participants
Where: 33 sitesin 3 countries
Study dates: Mar 2010to Nov 2011
Phase: Phase 2
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

Major criteria include:

A diagnosis of a relapsing form of MS
Treatment with natalizumab according to locally approved prescribing information
Other protocol defined inclusion/exclusion criteria may apply

Trial locations and contacts

33 sites in 3 countries.

Country

City, postcode or hospital

33 sites in 3 countries

United States20 sites

Research Site
Atlanta, Georgia, 30309
Research Site
Atlanta, Georgia, 30327
Research Site
Boston, Massachusetts, 2135
Research Site
Boston, Massachusetts, 2215
Research Site
Buffalo, New York, 14203
Research Site
Charlotte, North Carolina, 28207
Research Site
Chicago, Illinois, 60612
Research Site
Cleveland, Ohio, 44195
Research Site
Cullman, Alabama, 35058
Research Site
Des Moines, Iowa, 50314
Research Site
Fort Collins, Colorado
Research Site
Lake Barrington, Illinois, 60010
Research Site
Latham, New York, 12110
Research Site
Patchogue, New York, 11772
Research Site
Pompano Beach, Florida, 33060
Research Site
Raleigh, North Carolina, 27607
Research Site
Salt Lake City, Utah, 84103
Research Site
San Francisco, California, 94117
Research Site
Seattle, Washington, 98111
Research Site
Uniontown, Ohio

Other trials in United States

Germany7 sites

Research Site
Bochum, North Rhine-Westphalia, 44791
Research Site
Dresden, Saxony, 1307
Research Site
Freiburg im Breisgau, Baden-Wurttemberg, 79106
Research Site
Hamburg, Free and Hanseatic City of Hamburg, 20246
Research Site
Hennigsdorf, Brandenburg, 16761
Research Site
Marburg, Hesse, 35039
Research Site
München, Bavaria, 81675

Other trials in Germany

Spain6 sites

Research Site
Barcelona, Barcelona, 8035
Research Site
El Palmar, Murcia, 30120
Research Site
L'Hospitalet de Llobregat, Barcelona, 8907
Research Site
Málaga, Malaga, 29010
Research Site
Valencia, Valencia, 46009
Research Site
Valencia, Valencia, 46010

Other trials in Spain

About this study

Official title: Randomized Treatment Interruption of Natalizumab

This is a randomized, rater blinded trial in patients who interrupt treatment with natalizumab with or without being treated with other immunomodulatory drugs, or continue treatment with natalizumab.

The main purpose of this study is to find out the following, when participants stop taking natalizumab for 24 weeks:

when MS symptoms return, and
if other drugs for MS may help control MS symptoms during the natalizumab-interruption period.

This study will also explore how quickly the effects of natalizumab return after resuming natalizumab dosing.

Conditions: Relapsing Remitting Multiple Sclerosis
Being tested: natalizumab, interferon beta 1-a, methylprednisolone, IV placebo, glatiramer acetate
Keywords: MS
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
300 mg intravenous every 4 weeks
interferon beta 1-aDrug
30 ug intramuscular once per week
methylprednisoloneDrug
1000 mg intravenous every 4 weeks
IV placeboOther
placebo intravenous every 4 weeks
glatiramer acetateDrug
20 mg subcutaneous once daily

Study groups in NCT01071083
Study group	Role	What they receive
natalizumab	Active comparator	Not described Receives: Drug: natalizumab
IV placebo	Placebo comparator	Not described Receives: Other: IV placebo
interferon β-1a, glatiramer acetate, or methylprednisolone	Active comparator	Not described Receives: Drug: interferon beta 1-a; Drug: methylprednisolone; Drug: glatiramer acetate

What is being measured

The primary outcome is the main question the study is designed to answer.

Time Course to Return of Radiological and/or Clinical Evidence of Multiple Sclerosis Activity, as Measured by the Percentage of Subjects Who Met Magnetic Resonance Imaging (MRI) and/or Clinical Relapse Rescue Criteria.
Rescue criteria were: 1) central reader MRI finding of 1 new gadolinium-enhancing (Gd+) lesion of >0.8 cubic centimeters in volume or 2 or more Gd+ lesions of any size 2) clinical relapse. Clinical relapse was new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, as defined by: an increase of ≥1 grade in ≥2 functional scales of the Expanded Disability Status Scale (EDSS); an increase of ≥2 grades in 1 functional scale of the EDSS; or an increase of >0.5 in EDSS if the previous EDSS was ≤5.5, or ≥0.5 if the previous EDSS was >5.5
Measured: 28 Weeks

Secondary outcomes (1)

Time Course to Return of Radiological Activity, as Measured by the Percentage of Subjects Who Met Magnetic Resonance Imaging (MRI) Rescue Criteria.
MRI rescue criteria were the presence of 1 new gadolinium-enhancing (Gd+) lesion of >0.8 cubic centimeters in volume or 2 or more Gd+ lesions of any size, according to the central MRI reader.
Measured: 28 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2010Nov 2011

First posted19 Feb 2010 (estimated)
Study startMar 2010
Primary completionNov 2011
Study completionNov 2011

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 (2)Papers the sponsor has linked to this study.
Other trials for Relapsing Remitting Multiple SclerosisStudies 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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 175 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01071083
Sponsor's protocol ID: 101MS205
Acronym: RESTORE
Status last verified: Nov 2012
First submitted: 17 Feb 2010
Last updated: 19 Sep 2013
Results posted: Yes, on ClinicalTrials.gov

Publications

Fox RJ, Cree BAC, de Seze J, Gold R, Hartung HP, Jeffery D, Kappos L, Montalban X, Weinstock-Guttman B, Singh CM, Altincatal A, Belviso N, Avila RL, Ho PR, Su R, Engle R, Sangurdekar D, de Moor C, Fisher E, Kieseier BC, Rudick RA. Temporal Relationship Between Serum Neurofilament Light Chain and Radiologic Disease Activity in Patients With Multiple Sclerosis. Neurology. 2024 May 14;102(9):e209357. doi: 10.1212/WNL.0000000000209357. Epub 2024 Apr 22.
PubMed 38648580
Nakamura K, Brown RA, Narayanan S, Collins DL, Arnold DL; Alzheimer's Disease Neuroimaging Initiative. Diurnal fluctuations in brain volume: Statistical analyses of MRI from large populations. Neuroimage. 2015 Sep;118:126-32. doi: 10.1016/j.neuroimage.2015.05.077. Epub 2015 Jun 3.
PubMed 26049148

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 19 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomized Treatment Interruption of Natalizumab
ClinicalTrials.gov ID: NCT01071083
Acronym / sponsor ID: RESTORE / 101MS205
Conditions: Relapsing Remitting Multiple Sclerosis
Keywords: MS
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 175 participants (actual)
Lead sponsor: BiogenIndustry (pharma, biotech, devices)
Collaborators: Elan Pharmaceuticals
Study start: Mar 2010
Primary completion: Nov 2011 (actual)
Study completion: Nov 2011 (actual)
First posted: 19 Feb 2010 (estimated)
Results: Posted 30 Jan 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This is a randomized, rater blinded trial in patients who interrupt treatment with natalizumab with or without being treated with other immunomodulatory drugs, or continue treatment with natalizumab.

The main purpose of this study is to find out the following, when participants stop taking natalizumab for 24 weeks:

when MS symptoms return, and
if other drugs for MS may help control MS symptoms during the natalizumab-interruption period.

This study will also explore how quickly the effects of natalizumab return after resuming natalizumab dosing.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
natalizumab	Active comparator	Drug: natalizumab
IV placebo	Placebo comparator	Other: IV placebo
interferon β-1a, glatiramer acetate, or methylprednisolone	Active comparator	Drug: interferon beta 1-a, Drug: methylprednisolone, Drug: glatiramer acetate

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

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
natalizumab300 mg intravenous every 4 weeks	Drug	natalizumab
interferon beta 1-a30 ug intramuscular once per week	Drug	interferon β-1a, glatiramer acetate, or methylprednisolone
methylprednisolone1000 mg intravenous every 4 weeks	Drug	interferon β-1a, glatiramer acetate, or methylprednisolone
IV placeboplacebo intravenous every 4 weeks	Other	IV placebo
glatiramer acetate20 mg subcutaneous once daily	Drug	interferon β-1a, glatiramer acetate, or methylprednisolone

Primary outcome

Time Course to Return of Radiological and/or Clinical Evidence of Multiple Sclerosis Activity, as Measured by the Percentage of Subjects Who Met Magnetic Resonance Imaging (MRI) and/or Clinical Relapse Rescue Criteria.
Time frame: 28 Weeks
Rescue criteria were: 1) central reader MRI finding of 1 new gadolinium-enhancing (Gd+) lesion of >0.8 cubic centimeters in volume or 2 or more Gd+ lesions of any size 2) clinical relapse. Clinical relapse was new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, as defined by: an increase of ≥1 grade in ≥2 functional scales of the Expanded Disability Status Scale (EDSS); an increase of ≥2 grades in 1 functional scale of the EDSS; or an increase of >0.5 in EDSS if the previous EDSS was ≤5.5, or ≥0.5 if the previous EDSS was >5.5

1 secondary outcome

Time Course to Return of Radiological Activity, as Measured by the Percentage of Subjects Who Met Magnetic Resonance Imaging (MRI) Rescue Criteria.
Time frame: 28 Weeks

Results and safety

Results posted to the registry on 30 Jan 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Intravenous Placebo	42	35
Natalizumab	45	43
Interferon β-1a	17	12
Glatiramer Acetate	17	15
Methylprednisolone	54	46

Primary outcome: Time Course to Return of Radiological and/or Clinical Evidence of Multiple Sclerosis Activity, as Measured by the Percentage of Subjects Who Met Magnetic Resonance Imaging (MRI) and/or Clinical Relapse Rescue Criteria.

Time frame: 28 Weeks. Number. Unit: Percentage of subjects meeting criteria

Measure	Natalizumab n = 45	Intravenous Placebo n = 41	Interferon β-1a n = 14	Glatiramer Acetate n = 15	Methylprednisolone n = 52
Value	4.7	60.5	28.6	53.3	54.8

Population analysed: Of the randomized subjects, data from 167 subjects were used in efficacy analyses. Eight subjects were excluded from the analyses: 3 subjects had major protocol deviations and 5 subjects discontinued study participation prior to Week 4 Visit.

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Intravenous Placebo	1 of ?	35 of ?	Not reported
Natalizumab	1 of ?	38 of ?	Not reported
Interferon β-1a	1 of ?	15 of ?	Not reported
Glatiramer Acetate	1 of ?	15 of ?	Not reported
Methylprednisolone	1 of ?	42 of ?	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 38648580Fox RJ, Cree BAC, de Seze J, Gold R, Hartung HP, Jeffery D, Kappos L, Montalban X, Weinstock-Guttman B, Singh CM, Altincatal A, Belviso N, Avila RL, Ho PR, Su R, Engle R, Sangurdekar D, de Moor C, Fisher E, Kieseier BC, Rudick RA. Temporal Relationship Between Serum Neurofilament Light Chain and Radiologic Disease Activity in Patients With Multiple Sclerosis. Neurology. 2024 May 14;102(9):e209357. doi: 10.1212/WNL.0000000000209357. Epub 2024 Apr 22.
Derived from this study: PubMed 26049148Nakamura K, Brown RA, Narayanan S, Collins DL, Arnold DL; Alzheimer's Disease Neuroimaging Initiative. Diurnal fluctuations in brain volume: Statistical analyses of MRI from large populations. Neuroimage. 2015 Sep;118:126-32. doi: 10.1016/j.neuroimage.2015.05.077. Epub 2015 Jun 3.

Related trials for Relapsing Remitting Multiple Sclerosis

Active, not recruiting
Myrosinase Bioactivated Gglucoraphanin for the Treatment of Neurodegenerative Diseases (GRA-MYR-ND)
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Recruiting
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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.

The record lists no contact. Use the official record to reach the sponsor.

33 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing natalizumab, interferon beta 1-a and methylprednisolone in people with Relapsing Remitting Multiple Sclerosis, run by Biogen at 33 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

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 19 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in United States, Germany, Spain. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 30 Jan 2013). 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?

Time Course to Return of Radiological and/or Clinical Evidence of Multiple Sclerosis Activity, as Measured by the Percentage of Subjects Who Met Magnetic Resonance Imaging (MRI) and/or Clinical Relapse Rescue Criteria. (time frame: 28 Weeks). 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 NCT01071083, which also lists 2 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 19 Sep 2013.