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A Study to Evaluate the Safety, Tolerability and Efficacy of AIN457 in Patients With Relapsing-remitting Multiple Sclerosis

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01433250
Collaborator
(none)
39
Enrollment
14
Locations
2
Arms
28
Duration (Months)
2.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study will assess the long-term safety and tolerability of AIN457 in patients with relapsing-remitting multiple sclerosis (RRMS). In addition the long-term pattern of maintenance of efficacy and health related quality of life will be explored.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
39 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open Label Extension Study to Evaluate the Safety, Tolerability and Efficacy of AIN457 in Patients With Relapsing-remitting Multiple Sclerosis
Study Start Date :
Feb 1, 2012
Actual Primary Completion Date :
Jun 1, 2014
Actual Study Completion Date :
Jun 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: AIN 457 Core

(10mg/kg i.v.). AIN 457 core study /AIN 457 Extension

Drug: AIN457
(10mg/kg i.v.).
Other Names:
  • AIN457 core/ AIN extension

    		•
    Experimental: AIN457 Placebo Core

    (10mg/kg i.v.). AIN 457 placebo core study /AIN 457 Extension

    Drug: AIN457
    (10mg/kg i.v.).
    Other Names:
  • AIN Placebo / AIN Extension

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Measure: Number of Subjects With Adverse Events, Number of Abnormalities in Safety Assessments [97 weeks]

      Safety outcomes will be described in Adverse events section as there was not an efficacy primary outcome

    Secondary Outcome Measures

    1. Distribution of Patients With Relapses to End of Study (EOS) (All Subjects) [week 97]

      Description: number of relapses based on neurological assessments and EDSS

    2. Number Lesions Measured in the Brain by Magnetic Resonance Imaging. T1 Weighted MRI [weeks 13,25,37,53,73 and 97]

      Measures of absolute number of gadolinium [Gd]-enhancing lesions on T1-weighted scans

    3. Number Lesions Measured in the Brain by Magnetic Resonance Imaging. T2 Weighted MRI [weeks 13,25,37,53,73 and 97]

      Measures of absolute number of gadolinium [Gd]-enhancing lesions on T2-weighted lesions

    4. Change in Brain Volume at End of Study. [week 97]

      Change in volume from start to end of study

    5. Measure of Disability: Expanded Disability Status Scale (EDSS). [Baseline to week 97]

      The EDSS is a scale for assessing neurological impairment in MS (Kurtzke 1983) including (1) a series of scores in each of eight functional systems, and (2) the EDSS steps (ranging from 0 (normal) to 10 (death due to MS). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, Cerebral and Other functions.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 55 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Was exposed to AIN457 or placebo in study CAIN457B2201 and completed the CAIN457B2201 study, up to at and including Visit 10 (week 24).
    Exclusion Criteria:
    1. Have been treated with:

    • immunosuppressive medications such as azathioprine or methotrexate within 1 month prior to enrollment, if lymphocyte count normal.

    • immunoglobulins and/or monoclonal antibodies (with the exception of AIN457) within 2 month prior to enrollment, or if the immunosuppressive effects are likely to persist at enrollment (such as presence of B cell depletion after rituximab treatment).

    1. Have received total lymphoid irradiation, bone marrow transplantation, alemtuzumab, cladribine, cyclophosphamide, mitoxantrone or other immunosuppressive treatments with long-lasting (over 6 months) or permanent effects.

    2. Have received any live or live attenuated vaccines (including live vaccines for varicella-zoster virus or measles) within 2 months prior to enrollment.

    3. A diagnosis of chronic disease of the immune system other than MS, or of an immunodeficiency syndrome.

    4. Current severe depression.

    5. Pregnant or nursing (lactating) women.

    6. Malignancy diagnosed since enrollment in the core study (except for successfully-treated basal or squamous cell carcinoma of skin).

    7. A new diagnosis of diabetes

    8. Positive testing for tuberculosis (QuantiFeron or chest X-ray).

    9. Subjects with clinically significant cardiac abnormalities

    10. Unable or unwilling to undergo multiple venipunctures

    11. Unable to undergo MRI scans due to newly acquired claustrophobia or metallic implants incompatible with MRI.

    Other protocol-defined inclusion/exclusion criteria may apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Hradec Kralove Czech Republic 500 05
    2 Novartis Investigative Site Ostrava-Moravska Ostrava Czech Republic
    3 Novartis Investigative Site Ostrava Czech Republic
    4 Novartis Investigative Site Praha 2 Czech Republic 128 08
    5 Novartis Investigative Site Teplice Czech Republic 415 29
    6 Novartis Investigative Site Kazan Russian Federation 420021
    7 Novartis Investigative Site Moscow Russian Federation 129128
    8 Novartis Investigative Site Nizhny Novgorod Russian Federation 603155
    9 Novartis Investigative Site Smolensk Russian Federation 214019
    10 Novartis Investigative Site Kharkiv Ukraine 61068
    11 Novartis Investigative Site Kharkiv Ukraine
    12 Novartis Investigative Site Kiev Ukraine
    13 Novartis Investigative Site Odessa Ukraine 65025
    14 Novartis Investigative Site Vinnitsya Ukraine 21005

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01433250
    Other Study ID Numbers:
    • CAIN457B2201E1
    • 2011-001629-25
    First Posted:
    Sep 13, 2011
    Last Update Posted:
    Mar 14, 2016
    Last Verified:
    Feb 1, 2016
    Keywords provided by Novartis Pharmaceuticals
    Multiple Sclerosis,
    demyelinating autoimmune diseases,
    interleukin-17,
    monoclonal human antibody
    Additional relevant MeSH terms:
    Multiple Sclerosis
    Multiple Sclerosis, Relapsing-Remitting
    Sclerosis
    Antibodies, Monoclonal

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title AIN457 Core / AIN457 Extension AIN Placebo/ AIN457 Extension
    Arm/Group Description AIN in core study , continued AIN in extension study ( 10 mg/Kg iv every four weeks) Placebo in core study and AIN in extension study (10 mg/kg iv every four weeks)
    Period Title: Overall Study
    STARTED 22 17
    COMPLETED 19 14
    NOT COMPLETED 3 3

    Baseline Characteristics

    Arm/Group Title AIN457/ AIN457 Placebo/AIN457 Total
    Arm/Group Description AIN in core study , continued AIN in extension study Placebo for core study and AIN in extension study Total of all reporting groups
    Overall Participants 22 17 39
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    36.1
    (10)
    34.2
    (8.71)
    35.3
    (9.39)
    Sex: Female, Male (Count of Participants)
    Female
    12
    54.5%
    12
    70.6%
    24
    61.5%
    Male
    10
    45.5%
    5
    29.4%
    15
    38.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    4.5%
    0
    0%
    1
    2.6%
    Not Hispanic or Latino
    20
    90.9%
    16
    94.1%
    36
    92.3%
    Unknown or Not Reported
    1
    4.5%
    1
    5.9%
    2
    5.1%

    Outcome Measures

    1. Primary Outcome
    Title Measure: Number of Subjects With Adverse Events, Number of Abnormalities in Safety Assessments
    Description Safety outcomes will be described in Adverse events section as there was not an efficacy primary outcome
    Time Frame 97 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title AIN/AIN PBO/AIN
    Arm/Group Description AIN core 24 weeks/AIN extension 1 year placebo first 24 weeks/ AIN extension for 52 weeks
    Measure Participants 22 17
    Number [participants]
    12
    54.5%
    8
    47.1%
    2. Secondary Outcome
    Title Distribution of Patients With Relapses to End of Study (EOS) (All Subjects)
    Description Description: number of relapses based on neurological assessments and EDSS
    Time Frame week 97

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title AIN/AIN PBO/AIN
    Arm/Group Description AIN core 24 weeks/AIN extension 1 year placebo first 24 weeks/ AIN extension for 52 weeks
    Measure Participants 22 17
    Number [Participants]
    9
    40.9%
    5
    29.4%
    3. Secondary Outcome
    Title Number Lesions Measured in the Brain by Magnetic Resonance Imaging. T1 Weighted MRI
    Description Measures of absolute number of gadolinium [Gd]-enhancing lesions on T1-weighted scans
    Time Frame weeks 13,25,37,53,73 and 97

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title AIN/AIN PBO/AIN
    Arm/Group Description AIN core 24 weeks/AIN extension 1 year placebo first 24 weeks/ AIN extension for 52 weeks
    Measure Participants 22 17
    week 13 T1 (n=22, 16)
    0.8
    2.0
    week 25 T1 (n=22, 16)
    0.6
    1.9
    week 37 T1 (n=22, 15)
    1.0
    0.8
    week 53 T1 (n=14, 6)
    0.3
    0.3
    wk 73 T1 (n=11,9)
    0.6
    0.2
    EOT (n=15,13)
    0.7
    0.5
    4. Secondary Outcome
    Title Number Lesions Measured in the Brain by Magnetic Resonance Imaging. T2 Weighted MRI
    Description Measures of absolute number of gadolinium [Gd]-enhancing lesions on T2-weighted lesions
    Time Frame weeks 13,25,37,53,73 and 97

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title AIN/AIN PBO/AIN
    Arm/Group Description AIN core 24 weeks/AIN extension 1 year placebo first 24 weeks/ AIN extension for 52 weeks
    Measure Participants 22 17
    week 13 T2 (n=22, 16)
    1.3
    2.2
    week 25 T2 (n=22, 16)
    0.8
    2.4
    week 37 T2 (n=22, 15)
    1.3
    1.3
    week 53 T2 (n=14, 6)
    0.4
    0.7
    wk 73 T2 (n=11,9)
    1.3
    0.9
    EOT T2 (n=15,13)
    1.1
    .07
    5. Secondary Outcome
    Title Change in Brain Volume at End of Study.
    Description Change in volume from start to end of study
    Time Frame week 97

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title AIN/AIN PBO/AIN
    Arm/Group Description AIN core 24 weeks/AIN extension 1 year placebo first 24 weeks/ AIN extension for 52 weeks
    Measure Participants 22 17
    Mean (Standard Deviation) [ml]
    -14.8968
    (63.73027)
    -30.4346
    (31.21800)
    6. Secondary Outcome
    Title Measure of Disability: Expanded Disability Status Scale (EDSS).
    Description The EDSS is a scale for assessing neurological impairment in MS (Kurtzke 1983) including (1) a series of scores in each of eight functional systems, and (2) the EDSS steps (ranging from 0 (normal) to 10 (death due to MS). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, Cerebral and Other functions.
    Time Frame Baseline to week 97

    Outcome Measure Data

    Analysis Population Description
    Not all patients may have been available at all time points for EDSS evaluation
    Arm/Group Title AIN/AIN PBO/AIN
    Arm/Group Description AIN core 24 weeks/AIN extension 1 year placebo first 24 weeks/ AIN extension for 52 weeks
    Measure Participants 22 17
    Baseline score 0
    1
    4.5%
    0
    0%
    Baseline score 1.0
    0
    0%
    2
    11.8%
    Baseline score 1.5
    5
    22.7%
    5
    29.4%
    Baseline score 2.0
    5
    22.7%
    2
    11.8%
    Baseline score 2.5
    1
    4.5%
    1
    5.9%
    Baseline score 3.0
    2
    9.1%
    4
    23.5%
    Baseline score 3.5
    2
    9.1%
    0
    0%
    Baseline score 4.0
    1
    4.5%
    1
    5.9%
    Baseline score 4.5
    2
    9.1%
    2
    11.8%
    Baseline score 5.0
    1
    4.5%
    0
    0%
    Baseline score 6.0
    1
    4.5%
    0
    0%
    WK25 score 0
    2
    9.1%
    0
    0%
    WK25 score 1
    1
    4.5%
    2
    11.8%
    WK25 score 1.5
    4
    18.2%
    5
    29.4%
    WK25 score 2.0
    4
    18.2%
    1
    5.9%
    WK25 score 2.5
    2
    9.1%
    1
    5.9%
    WK25 score 3.0
    2
    9.1%
    4
    23.5%
    WK25 score 4.0
    1
    4.5%
    1
    5.9%
    WK25 score 4.5
    3
    13.6%
    1
    5.9%
    WK25 score 5.0
    1
    4.5%
    0
    0%
    WK25 score 5.5
    0
    0%
    1
    5.9%
    WK25 score 6.0
    1
    4.5%
    0
    0%
    WK25 score 6.5
    1
    4.5%
    0
    0%
    Safety Week 53 score 0
    1
    4.5%
    0
    0%
    Safety Week 53 score 1.0
    1
    4.5%
    1
    5.9%
    Safety Week 53 score 1.5
    3
    13.6%
    3
    17.6%
    Safety Week 53 score 2.0
    4
    18.2%
    0
    0%
    Safety Week 53 score 3.0
    1
    4.5%
    1
    5.9%
    Safety Week 53 score 3.5
    1
    4.5%
    0
    0%
    Safety Week 53 score 4.0
    0
    0%
    1
    5.9%
    Safety Week 53 score 5.0
    1
    4.5%
    0
    0%
    Safety Week 53 score 5.5
    2
    9.1%
    0
    0%
    Safety Week 53 score 6.0
    1
    4.5%
    0
    0%
    WK73 score 0
    1
    4.5%
    1
    5.9%
    WK73 score 1.0
    2
    9.1%
    1
    5.9%
    WK73 score 1.5
    1
    4.5%
    5
    29.4%
    WK73 score 2.0
    2
    9.1%
    0
    0%
    WK73 score 3.0
    0
    0%
    1
    5.9%
    WK73 score 4.0
    1
    4.5%
    0
    0%
    WK73 score 5.5
    1
    4.5%
    0
    0%
    WK73 score 6.0
    1
    4.5%
    0
    0%
    End of treatment score 0
    1
    4.5%
    1
    5.9%
    End of treatment score1.0
    2
    9.1%
    1
    5.9%
    End of treatment score 1.5
    2
    9.1%
    5
    29.4%
    End of treatment score 2.0
    2
    9.1%
    1
    5.9%
    End of treatment score 2.5
    2
    9.1%
    1
    5.9%
    End of treatment score 3.0
    0
    0%
    3
    17.6%
    End of treatment score 3.5
    1
    4.5%
    0
    0%
    End of treatment score 4.0
    2
    9.1%
    0
    0%
    End of treatment score 4.5
    0
    0%
    1
    5.9%
    End of treatment score 5.5
    0
    0%
    1
    5.9%
    End of treatment score 6.0
    1
    4.5%
    0
    0%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Placebo(Core)/AIN457(Extension) AIN457(Core)/AIN457(Extension)
    Arm/Group Description Placebo(core)/AIN457(extension) AIN457(core)/AIN457(extension)
    All Cause Mortality
    Placebo(Core)/AIN457(Extension) AIN457(Core)/AIN457(Extension)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Placebo(Core)/AIN457(Extension) AIN457(Core)/AIN457(Extension)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/17 (0%) 2/22 (9.1%)
    Injury, poisoning and procedural complications
    Radius fracture 0/17 (0%) 1/22 (4.5%)
    Musculoskeletal and connective tissue disorders
    Osteochondrosis 0/17 (0%) 1/22 (4.5%)
    Other (Not Including Serious) Adverse Events
    Placebo(Core)/AIN457(Extension) AIN457(Core)/AIN457(Extension)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 8/17 (47.1%) 7/22 (31.8%)
    Cardiac disorders
    Angina pectoris 1/17 (5.9%) 0/22 (0%)
    Cardiomyopathy 1/17 (5.9%) 0/22 (0%)
    Gastrointestinal disorders
    Gastritis 1/17 (5.9%) 0/22 (0%)
    Infections and infestations
    Cystitis 1/17 (5.9%) 0/22 (0%)
    Laryngitis 1/17 (5.9%) 0/22 (0%)
    Nasopharyngitis 1/17 (5.9%) 1/22 (4.5%)
    Pharyngitis 0/17 (0%) 2/22 (9.1%)
    Respiratory tract infection viral 1/17 (5.9%) 2/22 (9.1%)
    Rhinitis 1/17 (5.9%) 0/22 (0%)
    Investigations
    C-reactive protein increased 1/17 (5.9%) 0/22 (0%)
    Metabolism and nutrition disorders
    Overweight 1/17 (5.9%) 0/22 (0%)
    Nervous system disorders
    Headache 1/17 (5.9%) 0/22 (0%)
    Migraine 1/17 (5.9%) 0/22 (0%)
    Psychiatric disorders
    Anxiety disorder 0/17 (0%) 2/22 (9.1%)
    Reproductive system and breast disorders
    Uterine cervical erosion 1/17 (5.9%) 0/22 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 0/17 (0%) 2/22 (9.1%)
    Vascular disorders
    Hypertension 1/17 (5.9%) 0/22 (0%)
    Varicose vein 0/17 (0%) 2/22 (9.1%)

    Limitations/Caveats

    Further development of secukinumab in MS is not being pursued and the extension study , CAIN457B2201E1, further enrollment stopped . Not completing enrollment of this study was not related to the safety or tolerability concerns observed in the study.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    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 the pooled data (ie, data from all sites) in the clinical trial

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone 862-778-8300
    Email
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01433250
    Other Study ID Numbers:
    • CAIN457B2201E1
    • 2011-001629-25
    First Posted:
    Sep 13, 2011
    Last Update Posted:
    Mar 14, 2016
    Last Verified:
    Feb 1, 2016