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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-001442-15 | EudraCT Number |
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Based on recent publications, determination of natalizumub washout period was no longer relevant.
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This study evaluated disease control during different lengths of treatment transition from natalizumab to fingolimod.
Patient were screened, signed an informed consent at visit 1, at the 2nd visit, all patient received a baseline infusion of Natalizumub and subsequently randomized to one of 3 treatment arms. At the randomization visit, the Washout Phase started, and eligible patients were randomized 1:1:1 to one of three treatment groups:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 8-week washout + Fingolimod (FTY720) | Experimental | 8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day |
|
| 12-week washout + Fingolimod (FTY720) | Experimental | 12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day |
|
| 16-week washout + Fingolimod (FTY720) | Experimental | 16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fingolimod | Drug | Fingolimod 0.5 mg capsules for oral administration once daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) Through 8 Weeks of Fingolimod Treatment | Active lesions were measured on brain MRI scans, performed at week 8, compared to the prior scan. The primary variable was analyzed by fitting a negative binomial regression model adjusted for washout group. | Number of active T2 lesions from last natalizumab dose through 8 weeks of fingolimod treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) up to the Initiation of Fingolimod Treatment | Lesions were measured by MRIs and the number of active (new or newly enlarging) T2 lesions was calculated from baseline to beginning of treatment. | 8, 12 and 16 weeks (number of active T2 lesions during the washout period only) |
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Inclusion Criteria:
Patients must:
Exclusion Criteria:
Patients with:
Other protocol-defined inclusion/exclusion criteria may apply
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Box Hill | Victoria | 3128 | Australia | ||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28856176 | Derived | Derfuss T, Kovarik JM, Kappos L, Savelieva M, Chhabra R, Thakur A, Zhang Y, Wiendl H, Tomic D. alpha4-integrin receptor desaturation and disease activity return after natalizumab cessation. Neurol Neuroimmunol Neuroinflamm. 2017 Aug 25;4(5):e388. doi: 10.1212/NXI.0000000000000388. eCollection 2017 Sep. |
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142 Participants were randomized to 3 washout groups in a ratio of 1:1:1
Of the 158 patients screened, 142 patients were randomized.
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| ID | Title | Description |
|---|---|---|
| FG000 | 8-week Washout + Fingolimod (FTY720) | 8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day |
| FG001 | 12-week Washout + Fingolimod (FTY720) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Placebo | Drug | Matching placebo in capsules for oral administration once daily. |
|
| Number of Active (New or Newly Enlarging) T2 Lesions During the First 8 Weeks of Fingolimod Treatment | Lesions were measured by MRIs and the number of active (new or newly enlarging) T2 lesions was calculated for first 8 weeks of fingolimod treatment. | Number of active T2 lesions during 8 wks of fingolimod treatment |
| Number of Active (New or Newly Enlarging) T2 Lesions During the 24 Weeks After the Last Natalizumab Infusion (Baseline) | Lesions will be measured by MRIs and the number of active (new or newly enlarging) T2 lesions will be calculated for 24 weeks from baseline. | Baseline up to 24 weeks |
| Change From Baseline in Expanded Disability Status Scale (EDSS) by Washout Group | Kurtzke's Expanded Disability Status Scale (EDSS) measures the changes in neurologic impairment, either chronic (progression over time), or acute (MS relapses). The EDSS steps range from 0 (normal) to 10 (death due to MS). Relapse severity is assessed based on severity of neurologic impairment as evaluated using the EDSS. | Baseline to week 16 and week 32 |
| Cumulative Number of Gadolinium-enhancing T1 Lesions From the Last Natalizumab Infusion | Gadolinium-enhancing lesions will be measured on post-contrast T1-weighted brain MRI scans | 8 weeks and 24 weeks |
| Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Washout Period | Adverse events were summarized by the number of patients having any adverse event overall. | Baseline to maximum of 16 weeks |
| Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Fingolimod Treatment | Adverse events were summarized by the number of patients having any adverse event overall. | Baseline to maximum of 16 weeks |
| Heidelberg |
| Victoria |
| 3084 |
| Australia |
| Novartis Investigative Site | Vienna | 1010 | Austria |
| Novartis Investigative Site | Prague | 128 08 | Czechia |
| Novartis Investigative Site | Prague | 150 00 | Czechia |
| Novartis Investigative Site | Teplice | 415 29 | Czechia |
| Novartis Investigative Site | Helsinki | 00100 | Finland |
| Novartis Investigative Site | Ostfildern | Baden-Wurttemberg | 73760 | Germany |
| Novartis Investigative Site | Celle | Germany | 29223 | Germany |
| Novartis Investigative Site | Bad Mergentheim | 97980 | Germany |
| Novartis Investigative Site | Berlin | 10713 | Germany |
| Novartis Investigative Site | Berlin | 12163 | Germany |
| Novartis Investigative Site | Bielefeld | 33647 | Germany |
| Novartis Investigative Site | Bochum | 44791 | Germany |
| Novartis Investigative Site | Erbach im Odenwald | 64711 | Germany |
| Novartis Investigative Site | Erfurt | 99089 | Germany |
| Novartis Investigative Site | Hamburg | 22083 | Germany |
| Novartis Investigative Site | Itzehoe | 25524 | Germany |
| Novartis Investigative Site | Kandel | 76870 | Germany |
| Novartis Investigative Site | Krefeld | 47805 | Germany |
| Novartis Investigative Site | Leipzig | 04275 | Germany |
| Novartis Investigative Site | Münster | 48149 | Germany |
| Novartis Investigative Site | Neuburg am Inn | 86633 | Germany |
| Novartis Investigative Site | Neuruppin | 16816 | Germany |
| Novartis Investigative Site | Rüdersdorf | 15562 | Germany |
| Novartis Investigative Site | Siegen | 57076 | Germany |
| Novartis Investigative Site | Ulm | 89073 | Germany |
| Novartis Investigative Site | Athens | GR | 115 25 | Greece |
| Novartis Investigative Site | Ioannina | GR | 455 00 | Greece |
| Novartis Investigative Site | Thessaloniki | GR | 570 10 | Greece |
| Novartis Investigative Site | Athens | GR 151 25 | Greece |
| Novartis Investigative Site | Athens | GR-106 76 | Greece |
| Novartis Investigative Site | Budapest | 1074 | Hungary |
| Novartis Investigative Site | Budapest | 1085 | Hungary |
| Novartis Investigative Site | Ashkelon | 78278 | Israel |
| Novartis Investigative Site | Jerusalem | 91120 | Israel |
| Novartis Investigative Site | Milan | MI | 20132 | Italy |
| Novartis Investigative Site | Cefalù | PA | 90015 | Italy |
| Novartis Investigative Site | Málaga | Andalusia | 29010 | Spain |
| Novartis Investigative Site | Seville | Andalusia | 41009 | Spain |
| Novartis Investigative Site | Barcelona | Barcelona | 08025 | Spain |
| Novartis Investigative Site | Barcelona | Catalonia | 08035 | Spain |
| Novartis Investigative Site | Madrid | Madrid | 28046 | Spain |
| Novartis Investigative Site | Basel | 4031 | Switzerland |
12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day
| FG002 | 16-week Washout + Fingolimod (FTY720) | 16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day |
| Full Analysis Set (FAS) |
|
| Modified Full Analysis Set |
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| COMPLETED |
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| NOT COMPLETED |
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Randomized set includes all subjects who receive a randomization number, regardless of whether or not they receive study medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | 8-week Washout + Fingolimod (FTY720) | 8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day |
| BG001 | 12-week Washout + Fingolimod (FTY720) | 12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day |
| BG002 | 16-week Washout + Fingolimod (FTY720) | 16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) Through 8 Weeks of Fingolimod Treatment | Active lesions were measured on brain MRI scans, performed at week 8, compared to the prior scan. The primary variable was analyzed by fitting a negative binomial regression model adjusted for washout group. | The modified Full Analysis Set (mFAS) included all patients in the Full Analysis Set who completed 8 weeks of fingolimod treatment and provided an MRI scan at this time point. The analysis of primary variable was performed on the mFAS. | Posted | Mean | Standard Deviation | Count of Active T2 Lesions | Number of active T2 lesions from last natalizumab dose through 8 weeks of fingolimod treatment |
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| Secondary | Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) up to the Initiation of Fingolimod Treatment | Lesions were measured by MRIs and the number of active (new or newly enlarging) T2 lesions was calculated from baseline to beginning of treatment. | The Full Analysis Set (FAS) included all randomized patients who had at least one recorded dose of natalizumab at the Week 0 visit, analyzed according to the washout group assigned at randomization | Posted | Mean | Standard Deviation | Count of active T2 lesions | 8, 12 and 16 weeks (number of active T2 lesions during the washout period only) |
| |||||||||||||||||||||||||||||||||
| Secondary | Number of Active (New or Newly Enlarging) T2 Lesions During the First 8 Weeks of Fingolimod Treatment | Lesions were measured by MRIs and the number of active (new or newly enlarging) T2 lesions was calculated for first 8 weeks of fingolimod treatment. | The Full Analysis Set (FAS) included all randomized patients who had at least one recorded dose of natalizumab at the Week 0 visit, analyzed according to the washout group assigned at randomization | Posted | Mean | Standard Deviation | Count of Active T2 Lesions | Number of active T2 lesions during 8 wks of fingolimod treatment |
| |||||||||||||||||||||||||||||||||
| Secondary | Number of Active (New or Newly Enlarging) T2 Lesions During the 24 Weeks After the Last Natalizumab Infusion (Baseline) | Lesions will be measured by MRIs and the number of active (new or newly enlarging) T2 lesions will be calculated for 24 weeks from baseline. | The Full Analysis Set (FAS) included all randomized patients who had at least one recorded dose of natalizumab at the Week 0 visit, analyzed according to the washout group assigned at randomization | Posted | Mean | Standard Deviation | Count of Active T2 Lesions | Baseline up to 24 weeks |
| |||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Expanded Disability Status Scale (EDSS) by Washout Group | Kurtzke's Expanded Disability Status Scale (EDSS) measures the changes in neurologic impairment, either chronic (progression over time), or acute (MS relapses). The EDSS steps range from 0 (normal) to 10 (death due to MS). Relapse severity is assessed based on severity of neurologic impairment as evaluated using the EDSS. | The Full Analysis Set (FAS) included all randomized patients who had at least one recorded dose of natalizumab at the Week 0 visit, analyzed according to the washout group assigned at randomization. | Posted | Mean | Standard Deviation | Units on a scale | Baseline to week 16 and week 32 |
| |||||||||||||||||||||||||||||||||
| Secondary | Cumulative Number of Gadolinium-enhancing T1 Lesions From the Last Natalizumab Infusion | Gadolinium-enhancing lesions will be measured on post-contrast T1-weighted brain MRI scans | The Full Analysis Set (FAS) included all randomized patients who had at least one recorded dose of natalizumab at the Week 0 visit, analyzed according to the washout group assigned at randomization. | Posted | Mean | Standard Deviation | Number of Gd enhanced T1 Lesions | 8 weeks and 24 weeks |
| |||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Washout Period | Adverse events were summarized by the number of patients having any adverse event overall. | The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod | Posted | Number | participants | Baseline to maximum of 16 weeks |
| ||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Fingolimod Treatment | Adverse events were summarized by the number of patients having any adverse event overall. | The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod | Posted | Number | participants | Baseline to maximum of 16 weeks |
|
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Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 8-week Washout + Fingolimod (FTY720) | 8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day | 2 | 50 | 17 | 50 | ||
| EG001 | 12-week Washout + Fingolimod (FTY720) | 12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day | 5 | 42 | 7 | 42 | ||
| EG002 | 16-week Washout + Fingolimod (FTY720) | 16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day | 4 | 50 | 14 | 50 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bradycardia | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Cholecystitis acute | Hepatobiliary disorders | MedDRA | Systematic Assessment |
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| Cholelithiasis | Hepatobiliary disorders | MedDRA | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
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| Femur fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
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| Electrocardiogram T wave inversion | Investigations | MedDRA | Systematic Assessment |
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| Heart rate decreased | Investigations | MedDRA | Systematic Assessment |
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| Epilepsy | Nervous system disorders | MedDRA | Systematic Assessment |
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| Multiple sclerosis relapse | Nervous system disorders | MedDRA | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA | Systematic Assessment |
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| Depression suicidal | Psychiatric disorders | MedDRA | Systematic Assessment |
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| Major depression | Psychiatric disorders | MedDRA | Systematic Assessment |
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| Mental disorder due to a general medical condition | Psychiatric disorders | MedDRA | Systematic Assessment |
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| Personality change | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
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| Oral herpes | Infections and infestations | MedDRA | Systematic Assessment |
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| Sinusitis | Infections and infestations | MedDRA | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
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Study was terminated due to new data on nataluzimab washout prior to treatment with other disease modifying treatments. The power to detect statistically significant differences between the washout groups based on the (-)binomial is estimated 30-40%.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharnaceuticals | 862-778-8300 |
| ID | Term |
|---|---|
| D020529 | Multiple Sclerosis, Relapsing-Remitting |
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D000068876 | Fingolimod Hydrochloride |
| ID | Term |
|---|---|
| D013110 | Sphingosine |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D011409 | Propylene Glycols |
| D006018 | Glycols |
| D000588 | Amines |
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