Relapsing-Remitting Multiple SclerosisPhase 2NCT01416155

Extension Study to Evaluate Safety and Efficacy of Natalizumab in Japanese Participants With Relapsing-Remitting Multiple Sclerosis

A Phase 2 study testing natalizumab in people with Relapsing-Remitting Multiple Sclerosis and Multiple Sclerosis, run by Biogen at 22 sites in Japan.

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

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Relapsing-Remitting Multiple Sclerosis, Multiple Sclerosis
What is being tested?: natalizumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 97 participants
Where: 22 sitesJapan
Study dates: Oct 2010to Dec 2014
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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Ability to understand the purpose and risks of the study and provide signed and dated informed consent and any authorizations required by local law.
Subjects who participated in and completed all protocol-related evaluations through Week 24 of Study 101MS203 (NCT01440101).
Subjects participating in study 101MS204 (NCT01416155) participated either in the open label pharmacokinetics-pharmacodynamics study or placebo-controlled study of natalizumab 300 mg q4wks (parts A and B of study 101MS203, respectively).
Subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 12 weeks after their last dose of study treatment.
Must be willing to remain free from concomitant immunosuppressive or immunomodulatory treatment (including interferon beta [IFNβ] and long-term systemic corticosteroids) for the duration of the study.

Who cannot join

Any significant change in medical history since Study 101MS203 (NCT01440101), including laboratory tests, or current clinically important condition that in the opinion of the Investigator would have excluded the subject's participation in the previous study. The Investigator must re-review the subject's medical fitness for participation and consider diseases that would preclude treatment.
Subjects from Study 101MS203 (NCT01440101) who discontinued study treatment due to an adverse event.
Subjects who are determined to be persistently positive for anti-BG0002 antibodies based on prior testing.
Treatment History
Treatment with any of the following medications between last dose of study treatment in Study 101MS203 (NCT01440101) and the start of this study: intravenous immunoglobulin (IVIg), plasmapheresis, cytapheresis, immunosuppressant medications (e.g., mitoxantrone, azathioprine, cyclophosphamide, methotrexate, cyclosporine, FTY720), immunomodulatory medications (including IFNβ and glatiramer acetate [GA]) total lymphoid irradiation, cladribine, T-cell or T-cell receptor vaccination, any murine protein, any other therapeutic monoclonal antibody, or any 4-aminopyridine or related products.
Miscellaneous

Show all 11Show fewer

For female subjects, unless postmenopausal for at least 1 year or surgically sterile (does not include tubal ligation), unwillingness to practice effective contraception, as defined by the Investigator, during the study. Women considering becoming pregnant while on study are to be excluded.
Female subjects who are currently pregnant or breast feeding, including subjects whose pregnancy test is positive at Week 0.
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 any other condition, clinical finding, or reason that in the opinion of the Investigator and/or the Sponsor makes the subject unsuitable for enrollment into the study.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

22 sites in 1 country.

City, postcode or hospital

22 sites in 1 country

Japan22 sites

Research Site
Bunkyo-ku, Tokyo, 113-8431
Research Site
Bunkyo-ku, Tokyo, 113-8519
Research Site
Chiba, Chiba, 260-8677
Research Site
Fukuoka, Fukuoka, 812-8582
Research Site
Hiroshima, Hiroshima, 734-8551
Research Site
Kawagoe, Saitama, 350-8550
Research Site
Kodaira, Tokyo, 187-8551
Research Site
Kyoto, Kyoto, 604-8453
Research Site
Kyoto, Kyoto, 606-8507
Research Site
Kyoto, Kyoto, 616-8255
Research Site
Morioka, Iwate, 020-8505
Research Site
Niigata, Niigata, 951-8520
Research Site
Osaka, Osaka, 556-0016
Research Site
Ōta-ku, Tokyo, 145-0065
Research Site
Sapporo, Hokkaido, 060-8648
Research Site
Sapporo, Hokkaido, 063-0005
Research Site
Sendai, Miyagi, 980-8574
Research Site
Suita, Osaka, 565-0871
Research Site
Tokorozawa, Saitama, 359-8513
Research Site
Tsukuba, Ibaraki, 305-8576
Research Site
Ube, Yamaguchi, 755-8505
Research Site
Yokohama, Kanagawa, 232-0024

Other trials in Japan

About this study

Official title: A Long-Term, Open-Label, Multicenter, Extension Study to Evaluate Safety and Efficacy of BG00002 in Japanese Subjects With Relapsing-Remitting Multiple Sclerosis

The primary objective of the study is to further evaluate the long-term safety and tolerability profiles of BG00002 (natalizumab) in Japanese participants with relapsing-remitting multiple sclerosis (RRMS). The secondary objective of this study is to further evaluate the long-term efficacy profile of BG00002 in Japanese participants with RRMS.

Read the detailed description

This is a multicenter, long-term, open-label, extension study in participants who have successfully completed Study 101MS203 (NCT01440101).

Conditions: Relapsing-Remitting Multiple Sclerosis, Multiple Sclerosis
Being tested: natalizumab
Medical subject headings: Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

natalizumabDrug
Also called Tysabri, BG00002

Study groups in NCT01416155
Study group	Role	What they receive
natalizumab	Experimental	300 mg intravenous (IV) infusions of natalizumab every 4 weeks until product is approved in Japan or development is discontinued in Japan, whichever comes first. Receives: Drug: natalizumab

What is being measured

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

Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs
An AE was any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigators, placed the subject at immediate risk of death (a life-threatening event); however, this did not include an event that, had it occurred in a more severe form, might have caused death; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigators, could have jeopardized the subject or may have required intervention to prevent one of the other outcomes listed in the definition above.
Measured: Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months
Number of Participants With Serum Antibodies to Natalizumab
Negative is defined as negative for antibodies at all post-baseline results. Transient positivity is defined as only 1 positive result. Persistent positivity is defined as 2 positive results separated by at least 6 to 12 weeks.
Measured: Day 1 up to approximately 50 months

Secondary outcomes (2)

Adjusted Annualized Relapse Rate
Clinical relapses are defined as new or recurrent neurologic symptoms, not associated with fever or infection, lasting for at least 24 hours, and accompanied by new objective neurological findings upon examination by the neurologist. The annualized relapse rate is calculated overall as the total number of relapses experienced in the study divided by the number of days followed in the study, and the ratio multiplied by 365. Obtained from a Poisson regression model, adjusted for the baseline relapse rate from study 101MS203 (NCT01440101).
Measured: Day 1 up to approximately 50 months
Mean Change From Baseline in the Assessment of Expanded Disability Status Scale (EDSS) up to Week 192
The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist.
Measured: Day 1 up to Week 192

Timeline

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

Oct 2010Dec 2014

First posted12 Aug 2011 (estimated)
Study startOct 2010
Primary completionDec 2014
Study completionDec 2014

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 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 97 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01416155
Sponsor's protocol ID: 101MS204
Status last verified: Dec 2015
First submitted: 24 Mar 2011
Last updated: 14 Jan 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Saida T, Kira JI, Kishida S, Yamamura T, Ohtsuka N, Ling Y, Torii S, Lucas N, Kuesters G, Steiner D, Tibung JT; Natalizumab Trial Principal Investigators. Safety and Efficacy of Natalizumab in Japanese Patients with Relapsing-Remitting Multiple Sclerosis: Open-Label Extension Study of a Phase 2 Trial. Neurol Ther. 2017 Jun;6(1):39-55. doi: 10.1007/s40120-016-0059-z. Epub 2016 Dec 5.
PubMed 27921221

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 14 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Long-Term, Open-Label, Multicenter, Extension Study to Evaluate Safety and Efficacy of BG00002 in Japanese Subjects With Relapsing-Remitting Multiple Sclerosis
ClinicalTrials.gov ID: NCT01416155
Acronym / sponsor ID: 101MS204
Conditions: Relapsing-Remitting Multiple Sclerosis, Multiple Sclerosis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 97 participants (actual)
Lead sponsor: BiogenIndustry (pharma, biotech, devices)
Study start: Oct 2010
Primary completion: Dec 2014 (actual)
Study completion: Dec 2014 (actual)
First posted: 12 Aug 2011 (estimated)
Results: Posted 14 Jan 2016

Clinical summary

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

Detailed description

This is a multicenter, long-term, open-label, extension study in participants who have successfully completed Study 101MS203 (NCT01440101).

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: natalizumab300 mg intravenous (IV) infusions of natalizumab every 4 weeks until product is approved in Japan or development is discontinued in Japan, whichever comes first.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Ability to understand the purpose and risks of the study and provide signed and dated informed consent and any authorizations required by local law.
Subjects who participated in and completed all protocol-related evaluations through Week 24 of Study 101MS203 (NCT01440101).
Subjects participating in study 101MS204 (NCT01416155) participated either in the open label pharmacokinetics-pharmacodynamics study or placebo-controlled study of natalizumab 300 mg q4wks (parts A and B of study 101MS203, respectively).
Subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 12 weeks after their last dose of study treatment.
Must be willing to remain free from concomitant immunosuppressive or immunomodulatory treatment (including interferon beta [IFNβ] and long-term systemic corticosteroids) for the duration of the study.

Key exclusion criteria (11 listed)

Any significant change in medical history since Study 101MS203 (NCT01440101), including laboratory tests, or current clinically important condition that in the opinion of the Investigator would have excluded the subject's participation in the previous study. The Investigator must re-review the subject's medical fitness for participation and consider diseases that would preclude treatment.
Subjects from Study 101MS203 (NCT01440101) who discontinued study treatment due to an adverse event.
Subjects who are determined to be persistently positive for anti-BG0002 antibodies based on prior testing.
Treatment History
Treatment with any of the following medications between last dose of study treatment in Study 101MS203 (NCT01440101) and the start of this study: intravenous immunoglobulin (IVIg), plasmapheresis, cytapheresis, immunosuppressant medications (e.g., mitoxantrone, azathioprine, cyclophosphamide, methotrexate, cyclosporine, FTY720), immunomodulatory medications (including IFNβ and glatiramer acetate [GA]) total lymphoid irradiation, cladribine, T-cell or T-cell receptor vaccination, any murine protein, any other therapeutic monoclonal antibody, or any 4-aminopyridine or related products.

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: Tysabri, BG00002	Drug	natalizumab

Primary outcome

Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs
Time frame: Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months
An AE was any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigators, placed the subject at immediate risk of death (a life-threatening event); however, this did not include an event that, had it occurred in a more severe form, might have caused death; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigators, could have jeopardized the subject or may have required intervention to prevent one of the other outcomes listed in the definition above.
Number of Participants With Serum Antibodies to Natalizumab
Time frame: Day 1 up to approximately 50 months
Negative is defined as negative for antibodies at all post-baseline results. Transient positivity is defined as only 1 positive result. Persistent positivity is defined as 2 positive results separated by at least 6 to 12 weeks.

2 secondary outcomes

Adjusted Annualized Relapse Rate
Time frame: Day 1 up to approximately 50 months
Mean Change From Baseline in the Assessment of Expanded Disability Status Scale (EDSS) up to Week 192
Time frame: Day 1 up to Week 192

Results and safety

Results posted to the registry on 14 Jan 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Natalizumab	97	39

Primary outcome: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs

Time frame: Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months. Number. Unit: participants

Measure	Natalizumab n = 97
Participants with an event	92
Participants with a moderate or severe event	52
Participants with a severe event	10
Participants with an event related to study drug	33
Participants with an SAE	29
Participants with an SAE related to study drug	7
Participants discontinuing treatment due to event	10
Participants withdrawing from study due to event	10

Population analysed: Safety population: all participants who received at least 1 dose of study treatment.

Primary outcome: Number of Participants With Serum Antibodies to Natalizumab

Time frame: Day 1 up to approximately 50 months. Number. Unit: participants

Measure	Natalizumab n = 96
Participants negative	91
Participants positive at any time	5
Participants transiently positive	3
Participants positive at final evaluation only	2
Participants persistently positive	2

Population analysed: Immunogenicity population: all participants who had received at least 1 infusion of BG00002, were negative for BG00002 antibodies at baseline and had at least 1 nonmissing post-baseline assessment of antibody status.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Natalizumab	29 of 97 (29.9%)	78 of 97 (80.4%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 27921221Saida T, Kira JI, Kishida S, Yamamura T, Ohtsuka N, Ling Y, Torii S, Lucas N, Kuesters G, Steiner D, Tibung JT; Natalizumab Trial Principal Investigators. Safety and Efficacy of Natalizumab in Japanese Patients with Relapsing-Remitting Multiple Sclerosis: Open-Label Extension Study of a Phase 2 Trial. Neurol Ther. 2017 Jun;6(1):39-55. doi: 10.1007/s40120-016-0059-z. Epub 2016 Dec 5.

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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

22 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing natalizumab in people with Relapsing-Remitting Multiple Sclerosis and Multiple Sclerosis, run by Biogen at 22 sites in Japan.

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 5 inclusion and 11 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 14 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in Japan. 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 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 14 Jan 2016). 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?

Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs (time frame: Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months). The study lists 2 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 NCT01416155, 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 14 Jan 2016.