Relapsing Multiple SclerosisPhase 4ESCALATENCT02241785
Natalizumab as an Efficacy Switch in Participants With Relapsing Multiple Sclerosis After Failure on Other Therapies
A Phase 4 study testing natalizumab in people with Relapsing Multiple Sclerosis, run by Biogen at 11 sites in United States.
Trial summary
The primary objective of the study is to determine the efficacy of natalizumab (Tysabri, BG00002) in participants with relapsing forms of multiple sclerosis (MS) who have failed Gilenya or BRACET (Betaseron, Rebif, Avonex, Copaxone, Extavia, Tecfidera) as measured by the proportion of participants with no evidence of… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Relapsing 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
- 47 participants
- Where
- 11 sitesUnited States
- Study dates
- 30 Sep 2014to 2 May 2016
- 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
- Subjects of childbearing potential must practice effective contraception from Day -1 and be willing and able to continue contraception for duration of the study.
- Must have documented diagnosis of relapsing MS (McDonald 2010 Criteria [Polman 2011]) at Screening.
- Must have been treated with Gilenya or Betaseron, Rebif, Avonex, Copaxone, Extavia, Tecfidera (BRACET) for at least the 12 months prior to Screening with no interruption of treatment greater than 1 month. Prior treatment with natalizumab is allowed; however, there must be a minimum 1 year since last natalizumab infusion and the Screening visit of this study, and if discontinuation of natalizumab in the past was not due to intolerance, anti-natalizumab antibodies, or efficacy loss.
- Must have had disease activity in the 6 months prior to Screening while on Gilenya or BRACET (as defined by at least 1 gadolinium enhancing lesion OR at least 2 new T2 lesions compared with magnetic resonance imaging done within 12 months of screening OR clinical relapse, or Expanded Disability Status Scale [EDSS] progression of 1 point)
- Must have an EDSS score from 0 to 5.5 inclusive at Screening.
- Must have lymphocyte count that is documented as at or above the lower limit of normal (LLN) by the day before the first Tysabri infusion. If lymphocytes have not returned to LLN or above the day before the first Tysabri infusion (day 0), the subject has screen failed. The subject who screen fails is eligible to undergo Rescreening once; if additional Rescreening is considered, please contact the study medical monitor.
Who cannot join
- History or positive test result at Screening for human immunodeficiency virus.
- History or positive test result at Screening for hepatitis C virus antibody or current hepatitis B infection (defined as positive for hepatitis B surface antigen and/or hepatitis core antibody).
- Prior treatment with natalizumab (either commercially or through a clinical study) within 1 year of Day -1.
- Contraindications to treatment with natalizumab as described in the Prescribing Information for each of the participating countries.
- Known allergy to natalizumab or any of its ingredients, or known to be anti-natalizumab antibody positive.
- Diagnosis of primary progressive MS, secondary progressive MS, and/or progressive-relapsing MS.
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- An MS relapse that has occurred within the 30 days prior to Day -1 and/or the subject has not stabilized from a previous relapse prior to Day -1.
- Known active malignancies (subjects with cutaneous basal cell carcinoma that has been completely excised prior to study entry remain eligible).
- History of severe opportunistic infections (including progressive multifocal leukoencephalopathy) or any clinically significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, and renal, or other major disease, as determined by the Investigator
- Clinically severe active infection within 1 month prior to Screening.
- Females breastfeeding, pregnant, or planning to become pregnant; women who are not post-menopausal or surgically sterile who are unwilling to practice contraception; women who have a positive pregnancy test result at Day -1.
- Prior history of immunosuppressant use (e.g., mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate, cladribine, rituximab) in the last 12 months prior to Screening. Prior history of alemtuzumab use at any point in the past.
- NOTE: Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Research Site
Akron, Ohio, 44320
Research Site
Aurora, Colorado, 80045
Research Site
Cleveland, Ohio, 44195
Research Site
Des Moines, Iowa, 50314
Research Site
Fullerton, California, 92835
Research Site
Knoxville, Tennessee, 37922
Research Site
Plainview, New York, 11803
Research Site
Raleigh, North Carolina, 27607-6010
Research Site
Round Rock, Texas, 78681
Research Site
St Louis, Missouri, 63110
Research Site
Tacoma, Washington, 98405
About this study
Official title: A Phase 4 Multicenter, Open-Label, Single Arm Study to Evaluate Switching From BRACET/Gilenya® to Natalizumab in Subjects With Relapsing Forms of Multiple Sclerosis (MS)
The primary objective of the study is to determine the efficacy of natalizumab (Tysabri, BG00002) in participants with relapsing forms of multiple sclerosis (MS) who have failed Gilenya or BRACET (Betaseron, Rebif, Avonex, Copaxone, Extavia, Tecfidera) as measured by the proportion of participants with no evidence of disease activity (NEDA) at Year 1. The secondary objectives in this study population are: change in total T1 hypointense and total T2 hyperintense lesion volume; proportion of participants with NEDA at Year 2; evaluation of the impact of natalizumab on annualized relapse rate (ARR); and change in Multiple Sclerosis Impact Scale-29 (MSIS-29) physical impact score.
- Conditions
- Relapsing Multiple Sclerosis
- Being tested
- natalizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
natalizumabDrug
Also called BG00002, Tysabri
Administered as specified in the treatment arm
| Study group | Role | What they receive |
|---|---|---|
| natalizumab | Experimental | natalizumab 300 mg intravenously (IV) every 4 weeks Receives: Drug: natalizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Participants With No Evidence of Disease Activity (NEDA) From Reset Baseline (Week 8) to Week 56
The proportion of participants with NEDA, defined as follows: no Expanded Disability Status Scale (EDSS) progression (12-week sustained); no relapses; no gadolinium enhancing (Gd+) lesions; no new or enlarging T2 hyperintense lesions over 48 weeks after resetting the Baseline at Week 8 to remove contribution of combined unique active (CUA) lesions that occurred prior to Week 8, when natalizumab was not yet active. The EDSS quantifies disability in 8 functional systems. The final EDSS score is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.
Measured: Reset Baseline (Week 8) to Week 56
Secondary outcomes (4)
Change in T1 Unenhancing Lesion Volume and T2 Lesion Volume From Baseline (Day -1) to Reset Baseline (Week 8)
As measured by magnetic resonance imaging.
Measured: Baseline (Day -1) to Reset Baseline (Week 8)
Proportion of Participants With NEDA From Week 8 (Reset Baseline) to Week 104
Proportion of participants with NEDA from Week 8 (Reset Baseline) to Week 104 (with no 12-week confirmed EDSS progression determined at Week 116). NEDA was defined as follows: no EDSS progression (12-week sustained); no relapses; no Gd+ lesions; no new or enlarging T2 hyperintense lesions over 48 weeks after resetting the Baseline at Week 8 to remove contribution of CUA lesions that occurred prior to Week 8, when natalizumab was not yet active. The EDSS quantifies disability in 8 functional systems. The final EDSS score is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.
Measured: from Week 8 (Reset Baseline) to Week 104
Pre- and Post-Natalizumab Infusion Annualized Relapse Rate (ARR) Comparison at Month 12
An MS relapse was defined as the onset of new or recurrent neurological symptoms lasting at least 24 hours, accompanied by new objective abnormalities on a neurological examination, and not explained solely by non-MS processes such as fever, infection, severe stress, or drug toxicity. 95% confidence interval is based on a Poisson regression model.
Measured: From 12 months prior to natalizumab infusion and 12 months post-natalizumab infusion
Change in MSIS-29 Physical Impact Scores From Baseline (Day -1) to Reset Baseline (Week 8)
The MSIS-29 is a brief self-administered MS-specific instrument measuring physical (20 items) and mental/psychological (9 items) impact of MS. The physical score is generated by summing individual items and then transforming to a scale with a range of 0 to 100, where high scores indicate worse health.
Measured: Baseline (Day -1) to Reset Baseline (Week 8)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2014 (estimated)
- Study start30 Sep 2014
- Primary completion2 May 2016
- Study completion2 May 2016
Why it stopped: Business Decision
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.
- Other trials for Relapsing 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Biogen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02241785
- Sponsor's protocol ID
- 101MS409
- Other IDs
- 2013-005586-39
- Acronym
- ESCALATE
- Status last verified
- Apr 2017
- First submitted
- 12 Sep 2014
- Last updated
- 5 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 4 Multicenter, Open-Label, Single Arm Study to Evaluate Switching From BRACET/Gilenya® to Natalizumab in Subjects With Relapsing Forms of Multiple Sclerosis (MS)
- ClinicalTrials.gov ID
- NCT02241785
- Acronym / sponsor ID
- ESCALATE / 101MS409
- Conditions
- Relapsing Multiple Sclerosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business Decision
- Enrolment
- 47 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- 30 Sep 2014 (actual)
- Primary completion
- 2 May 2016 (actual)
- Study completion
- 2 May 2016 (actual)
- First posted
- 16 Sep 2014 (estimated)
- Results
- Posted 5 Jun 2017
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 determine the efficacy of natalizumab (Tysabri, BG00002) in participants with relapsing forms of multiple sclerosis (MS) who have failed Gilenya or BRACET (Betaseron, Rebif, Avonex, Copaxone, Extavia, Tecfidera) as measured by the proportion of participants with no evidence of disease activity (NEDA) at Year 1. The secondary objectives in this study population are: change in total T1 hypointense and total T2 hyperintense lesion volume; proportion of participants with NEDA at Year 2; evaluation of the impact of natalizumab on annualized relapse rate (ARR); and change in Multiple Sclerosis Impact Scale-29 (MSIS-29) physical impact score.
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: natalizumabnatalizumab 300 mg intravenously (IV) every 4 weeks |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Subjects of childbearing potential must practice effective contraception from Day -1 and be willing and able to continue contraception for duration of the study.
- Must have documented diagnosis of relapsing MS (McDonald 2010 Criteria [Polman 2011]) at Screening.
- Must have been treated with Gilenya or Betaseron, Rebif, Avonex, Copaxone, Extavia, Tecfidera (BRACET) for at least the 12 months prior to Screening with no interruption of treatment greater than 1 month. Prior treatment with natalizumab is allowed; however, there must be a minimum 1 year since last natalizumab infusion and the Screening visit of this study, and if discontinuation of natalizumab in the past was not due to intolerance, anti-natalizumab antibodies, or efficacy loss.
- Must have had disease activity in the 6 months prior to Screening while on Gilenya or BRACET (as defined by at least 1 gadolinium enhancing lesion OR at least 2 new T2 lesions compared with magnetic resonance imaging done within 12 months of screening OR clinical relapse, or Expanded Disability Status Scale [EDSS] progression of 1 point)
- Must have an EDSS score from 0 to 5.5 inclusive at Screening.
Key exclusion criteria (13 listed)
- History or positive test result at Screening for human immunodeficiency virus.
- History or positive test result at Screening for hepatitis C virus antibody or current hepatitis B infection (defined as positive for hepatitis B surface antigen and/or hepatitis core antibody).
- Prior treatment with natalizumab (either commercially or through a clinical study) within 1 year of Day -1.
- Contraindications to treatment with natalizumab as described in the Prescribing Information for each of the participating countries.
- Known allergy to natalizumab or any of its ingredients, or known to be anti-natalizumab antibody positive.
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: BG00002, TysabriAdministered as specified in the treatment arm | Drug | natalizumab |
Primary outcome
Proportion of Participants With No Evidence of Disease Activity (NEDA) From Reset Baseline (Week 8) to Week 56
Time frame: Reset Baseline (Week 8) to Week 56
The proportion of participants with NEDA, defined as follows: no Expanded Disability Status Scale (EDSS) progression (12-week sustained); no relapses; no gadolinium enhancing (Gd+) lesions; no new or enlarging T2 hyperintense lesions over 48 weeks after resetting the Baseline at Week 8 to remove contribution of combined unique active (CUA) lesions that occurred prior to Week 8, when natalizumab was not yet active. The EDSS quantifies disability in 8 functional systems. The final EDSS score is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.
4 secondary outcomes
Change in T1 Unenhancing Lesion Volume and T2 Lesion Volume From Baseline (Day -1) to Reset Baseline (Week 8)
Time frame: Baseline (Day -1) to Reset Baseline (Week 8)
Proportion of Participants With NEDA From Week 8 (Reset Baseline) to Week 104
Time frame: from Week 8 (Reset Baseline) to Week 104
Pre- and Post-Natalizumab Infusion Annualized Relapse Rate (ARR) Comparison at Month 12
Time frame: From 12 months prior to natalizumab infusion and 12 months post-natalizumab infusion
Change in MSIS-29 Physical Impact Scores From Baseline (Day -1) to Reset Baseline (Week 8)
Time frame: Baseline (Day -1) to Reset Baseline (Week 8)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing natalizumab in people with Relapsing Multiple Sclerosis, run by Biogen at 11 sites in United States.
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 13 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: stopped early, as of the sponsor's last update on 5 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. 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 5 Jun 2017). 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?
Proportion of Participants With No Evidence of Disease Activity (NEDA) From Reset Baseline (Week 8) to Week 56 (time frame: Reset Baseline (Week 8) to Week 56). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Jun 2017.