<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03783416</url>
  </required_header>
  <id_info>
    <org_study_id>012436</org_study_id>
    <secondary_id>2018-003686-34</secondary_id>
    <nct_id>NCT03783416</nct_id>
  </id_info>
  <brief_title>SIZOMUS Safety of Ixazomib Targeting Plasma Cells in Multiple Sclerosis</brief_title>
  <acronym>SIZOMUS</acronym>
  <official_title>Safety of Ixazomib Targeting Plasma Cells in Multiple Sclerosis: A Phase 1b Randomised, Double-blind, Placebo-controlled Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Queen Mary University of London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Takeda Pharmaceuticals International, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Queen Mary University of London</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study seeks to investigate safety and efficacy of ixazomib (NINLARO), a proteasome&#xD;
      inhibitor, in multiple sclerosis (MS). Participants will receive either ixazomib capsules or&#xD;
      placebo capsules for up to 24 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The production of antibodies in the form of oligoclonal bands (OCBs) from plasma cells (cells&#xD;
      involved in the body's immune response), is the hallmark of MS. Recent evidence suggests that&#xD;
      plasma cells are resident in the meninges (protective membranes of the brain and spinal cord)&#xD;
      of people with Multiple Sclerosis (pwMS). Ixazomib is a drug which has been effective in&#xD;
      treating multiple myeloma, a disease caused by aberrant plasma cells. The purpose of this&#xD;
      study is to investigate whether ixazomib can reduce or clear OCBs from the cerebrospinal&#xD;
      fluid (CSF) of pwMS. Participants will be randomly assigned to receive either ixazomib&#xD;
      capsules (active drug arm) or placebo capsules (placebo arm) for up to 24 months.&#xD;
      Participants with relapsing remitting MS (who are stable on disease modifying therapy) and&#xD;
      those with progressive MS (who are not on disease modifying therapy) will be invited to take&#xD;
      part in the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 20, 2020</start_date>
  <completion_date type="Anticipated">August 20, 2023</completion_date>
  <primary_completion_date type="Anticipated">August 20, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>This is a double-blind, randomised, placebo-controlled trial. Randomisation will be stratified by disease stage, i.e. RRMS (and established on DMT) versus progressive MS (and not on DMT). The expected study duration is 36 months (a 12-month recruitment period and a 24-month treatment period). There will be 72 participants: 48 on ixazomib; 24 on placebo.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety - Adverse events (AE) will be compared between active and placebo arm</measure>
    <time_frame>Baseline to 24 months</time_frame>
    <description>Proportion of AEs in the Ixazomib versus placebo arm in subjects with Relapsing Remitting Multiple Sclerosis (RRMS)&#xD;
Proportion of serious AEs (SAEs) in the Ixazomib versus placebo arm in subjects with RRMS&#xD;
Proportion of AEs in the Ixazomib versus placebo arm in subjects with progressive MS&#xD;
Proportion of serious AEs (SAEs) in the Ixazomib versus placebo arm in subjects with progressive MS&#xD;
Proportion of AEs in the Ixazomib versus placebo arm in all subjects (subjects with RRMS and subjects with progressive MS)&#xD;
Proportion of serious AEs (SAEs) in the Ixazomib versus placebo arm in all subjects (subjects with RRMS and subjects with progressive MS)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Efficacy - the proportion of OCB IgG negative subjects will be compared between active and placebo arm</measure>
    <time_frame>Baseline to 24 months</time_frame>
    <description>Proportion of all subjects (Relapsing Remitting Multiple Sclerosis and progressive Multiple Sclerosis subjects) negative for Oligoclonal Bands Immunoglobulin G (OCB IgG) antibodies measured in Cerebrospinal Fluid (CSF) in the Ixazomib versus placebo arm at 24 months&#xD;
Proportion of subjects negative for Oligoclonal Bands Immunoglobulin G (OCB IgG) antibodies measured in Cerebrospinal Fluid (CSF) in the Ixazomib versus placebo arm at 24 months in subjects with Relapsing Remitting Multiple Sclerosis (RRMS)&#xD;
Proportion of subjects negative for Oligoclonal Bands Immunoglobulin G (OCB IgG) antibodies measured in Cerebrospinal Fluid (CSF) in the Ixazomib versus placebo arm at 24 months in subjects with progressive Multiple Sclerosis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Magnetic Resonance Imaging (MRI)</measure>
    <time_frame>Baseline to 24 months</time_frame>
    <description>Change in T2 lesion load and gadolinium enhancing lesions on brain MRI with Ixazomib versus placebo arm at 24 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change In Expanded Disability Status Scale (EDSS) with Ixazomib versus placebo arm at 24 months. The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist</measure>
    <time_frame>Baseline to 24 months</time_frame>
    <description>Change in EDSS with ixazomib versus placebo at 24 months.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Exploratory endpoint - IgG FLC</measure>
    <time_frame>Baseline to 24 months</time_frame>
    <description>a. Proportion of all subjects who show reduction in total levels of Immunoglobulin G Free Light Chain (IgG FLC) in Cerebrospinal Fluid (CSF) at 24 months in the Ixazomib versus placebo arm.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory endpoint - CD19</measure>
    <time_frame>Baseline to 24 months</time_frame>
    <description>b. Proportion of all subjects who show change in levels of Cluster of Differentiation antigen 19 (CD 19) at 24 months in the Ixazomib versus placebo arm.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory endpoint - soluble CD 138</measure>
    <time_frame>Baseline to 24 months</time_frame>
    <description>c. Proportion of all subjects who show change in levels of soluble CD 138 at 24 months in the Ixazomib versus placebo arm</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory endpoint - CD 27</measure>
    <time_frame>Baseline to 24 months</time_frame>
    <description>d. Proportion of all subjects who show change in levels of soluble CD 27 at 24 months in the Ixazomib versus placebo arm</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory endpoint - neurofilament light chain</measure>
    <time_frame>Baseline to 24 months</time_frame>
    <description>e. Proportion of all subjects who show change in levels of neurofilament light chain at 24 months in the Ixazomib versus placebo arm</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory endpoint - neurofilament heavy chain</measure>
    <time_frame>Baseline to 24 months</time_frame>
    <description>f. Proportion of all subjects who show change in levels of neurofilament heavy chain at 24 months in the Ixazomib versus placebo arm</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory endpoint - neopterin</measure>
    <time_frame>Baseline to 24 months</time_frame>
    <description>g. Proportion of all subjects who show change in levels of neopterin at 24 months in the Ixazomib versus placebo arm</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory endpoint - cytokines profile</measure>
    <time_frame>Baseline to 24 months</time_frame>
    <description>h. Proportion of all subjects who show change in levels of cytokines profile at 24 months in the Ixazomib versus placebo arm</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory endpoint - GFAP</measure>
    <time_frame>Baseline to 24 months</time_frame>
    <description>i. Proportion of all subjects who show change in levels of Glial fibrillary acidic protein (GFAP) at 24 months in the Ixazomib versus placebo arm</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory endpoint - NCAM</measure>
    <time_frame>Baseline to 24 months</time_frame>
    <description>j. Proportion of all subjects who show change in levels of Neural cell adhesion molecule (NCAM) at 24 months in the Ixazomib versus placebo arm</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory endpoint - GAP43</measure>
    <time_frame>Baseline to 24 months</time_frame>
    <description>k. Proportion of all subjects who show change in levels of Growth Associated Protein 43 (GAP43) at 24 months in the Ixazomib versus placebo arm</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory endpoint - S100B</measure>
    <time_frame>Baseline to 24 months</time_frame>
    <description>l. Proportion of all subjects who show change in levels of S100 calcium-binding protein B (S100B) at 24 months in the Ixazomib versus placebo arm</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">72</enrollment>
  <condition>Relapsing Remitting Multiple Sclerosis</condition>
  <condition>Primary Progressive Multiple Sclerosis</condition>
  <condition>Secondary Progressive Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>Ixazomib (NINLARO®)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment will follow a 28-day cycle. Participants will take one Ixazomib (NINLARO) capsule orally on days 1, 8, and 15 of each 28-day cycle, followed by one treatment-free week, in sequence, for the duration of the trial.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Treatment will follow a 28-day cycle. Participants will take one placebo capsule orally on days 1, 8, and 15 of each 28-day cycle, followed by one treatment-free, in sequence, for the duration of the trial.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ixazomib (NINLARO®) capsules / Matching placebo capsules</intervention_name>
    <description>Participants will be treated for a maximum of 24 months</description>
    <arm_group_label>Ixazomib (NINLARO®)</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Each participant must meet all of the following inclusion criteria to be enrolled in the&#xD;
        study:&#xD;
&#xD;
          1. Male and female patients 18 to 65 years old at screening&#xD;
&#xD;
          2. Must have a diagnosis of MS, and:&#xD;
&#xD;
               -  Patients with RRMS must be on DMT&#xD;
&#xD;
               -  Patients with progressive MS must not be on DMT&#xD;
&#xD;
          3. Participants with RRMS must be on stable DMT (i.e. must not have had a relapse within&#xD;
             1 month prior to the screening visit). Patients on tecfidera, cladribine, ocrelizumab,&#xD;
             alemtuzumab, fingolimod or natalizumab must be enrolled with caution, at Chief&#xD;
             Investigator's (CI) discretion because of the lymphopenia caused by these drugs and&#xD;
             the risk of thrombocytopenia in 1-2 % of people after alemtuzumab&#xD;
&#xD;
          4. OCB positive CSF either from a previous CSF analysis or from the screening CSF&#xD;
             analysis&#xD;
&#xD;
          5. Able and willing to give written informed consent and comply with protocol&#xD;
             requirements with the understanding that consent may be withdrawn by the patient at&#xD;
             any time without prejudice to future medical care.&#xD;
&#xD;
          6. Agree to the use of effective contraception as follows:&#xD;
&#xD;
             Female patients must:&#xD;
&#xD;
               -  Be postmenopausal for at least 1 year before the screening visit (postmenopausal&#xD;
                  status confirmed by serum Follicle Stimulating Hormone (FSH) and oestrogen levels&#xD;
                  at screening or from a historical sample), OR&#xD;
&#xD;
               -  Surgically sterile, OR&#xD;
&#xD;
               -  If they are of childbearing potential, must agree to practice two effective&#xD;
                  methods of contraception concurrently from the time of signing the informed&#xD;
                  consent form until 90 days after the last dose of study drug, OR&#xD;
&#xD;
               -  Agree to practice true abstinence when this is in line with the preferred and&#xD;
                  usual lifestyle of the subject. Periodic abstinence e.g. calendar, ovulation,&#xD;
                  symptothermal, post-ovulation methods and withdrawal are not acceptable methods&#xD;
                  of contraception&#xD;
&#xD;
             Male patients must:&#xD;
&#xD;
               -  Even if surgically sterilized (post-vasectomy with documentation of azoospermia),&#xD;
                  agree to practice effective barrier contraception during the entire study&#xD;
                  treatment period and through to 90 days after the last dose of study drug, OR&#xD;
&#xD;
               -  Agree to practice true abstinence when this is in line with the preferred and&#xD;
                  usual lifestyle of the subject. Periodic abstinence e.g. calendar, ovulation,&#xD;
                  symptothermal, post-ovulation methods and withdrawal are not acceptable methods&#xD;
                  of contraception&#xD;
&#xD;
          7. Clinical laboratory values:&#xD;
&#xD;
               1. Absolute neutrophil count (ANC) ≥ 1 x 109/L&#xD;
&#xD;
               2. Platelet count ≥ 100 x 109/L&#xD;
&#xD;
               3. Total bilirubin ≤ 1.5 × the upper limit of the normal range (ULN)&#xD;
&#xD;
               4. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 3 × ULN.&#xD;
&#xD;
               5. Calculated creatinine clearance ≥ 30 mL/min&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants meeting any of the following exclusion criteria are not to be enrolled in&#xD;
             the study:&#xD;
&#xD;
               1. EDSS &gt; 8.5 at screening&#xD;
&#xD;
               2. MS relapse within 1 month prior to screening&#xD;
&#xD;
               3. Female patients who are lactating or have a positive serum pregnancy test at&#xD;
                  screening&#xD;
&#xD;
               4. Major surgery within 14 days before baseline&#xD;
&#xD;
               5. Any clinically relevant malignancy or infection, as per CI/PI (or delegate)&#xD;
                  decision, including a possible diagnosis of multiple myeloma: raised erythrocyte&#xD;
                  sedimentation rate (ESR) and positive urine Bence Jones protein at screening&#xD;
&#xD;
               6. Infection requiring systemic (intravenous) antibiotic therapy or other serious&#xD;
                  infection within 14 days before study enrolment. Urinary tract infections (UTIs)&#xD;
                  will be treated prior to baseline and may delay baseline&#xD;
&#xD;
               7. Evidence of current uncontrolled cardiovascular conditions, including&#xD;
                  uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic&#xD;
                  congestive heart failure, unstable angina, or myocardial infarction within 6&#xD;
                  months of screening&#xD;
&#xD;
               8. Systemic treatment, within 14 days before the first dose of ixazomib, with strong&#xD;
                  Cytochrome P450 Isoform 3A (CYP3A) inducers (rifampin, rifapentine, rifabutin,&#xD;
                  carbamazepine, phenytoin, phenobarbital), or use of St. John's Wort&#xD;
&#xD;
               9. History of active hepatitis B or C virus infection, or human immunodeficiency&#xD;
                  virus (HIV) positive or positive Tuberculin (TB) ELISPOT. If there is positive TB&#xD;
                  ELISPOT and the TB team decides to treat as latent TB, participants can be&#xD;
                  reassessed for inclusion after treatment&#xD;
&#xD;
              10. Any serious medical or psychiatric illness that could, in the investigator's&#xD;
                  opinion, potentially interfere with the completion of treatment according to this&#xD;
                  protocol&#xD;
&#xD;
              11. Known GI disease or GI procedure that could interfere with the oral absorption or&#xD;
                  tolerance of ixazomib including difficulty swallowing&#xD;
&#xD;
              12. Diagnosed or treated for malignancy within 2 years before study enrolment or&#xD;
                  previously diagnosed with another malignancy and have any evidence of residual&#xD;
                  disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type&#xD;
                  are not excluded if they have undergone complete resection&#xD;
&#xD;
              13. Patient has ≥ Grade 3 peripheral neuropathy, or Grade 2 with pain on clinical&#xD;
                  examination during the screening period&#xD;
&#xD;
              14. Participation in other clinical trials involving investigational (unlicensed)&#xD;
                  medicinal products, licensed medicinal products or alternative medicinal&#xD;
                  therapies, within 30 days of screening and throughout the duration of this trial.&#xD;
                  Participation in non-interventional, questionnaire or observational studies&#xD;
                  whilst enrolled in this study is permitted.&#xD;
&#xD;
              15. Patients that have previously been treated with ixazomib or participated in a&#xD;
                  study with ixazomib whether treated with ixazomib or placebo&#xD;
&#xD;
              16. Known allergy to any of the study medications, their analogues, or excipients in&#xD;
                  the various formulations of any agent&#xD;
&#xD;
              17. Any pre-existing central nervous system disease or involvement other than MS&#xD;
&#xD;
              18. History of uncontrolled drug or alcohol abuse within 6 months prior to screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Royal London Hospital, Barts Health NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <state>Greater London</state>
        <zip>E1 1BB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sharmilee Gnanapavan, MD</last_name>
      <phone>+44 2073777000</phone>
      <phone_ext>42157</phone_ext>
      <email>Sharmilee.gnanapavan@bartshealth.nhs.uk</email>
    </contact>
    <contact_backup>
      <last_name>Lucia Bianchi, PhD</last_name>
      <phone>+44 20 7882 2598</phone>
      <email>Lucia.bianchi@bartshealth.nhs.uk</email>
    </contact_backup>
    <investigator>
      <last_name>Sharmilee Gnanapavan, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>December 10, 2018</study_first_submitted>
  <study_first_submitted_qc>December 18, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 21, 2018</study_first_posted>
  <last_update_submitted>February 17, 2022</last_update_submitted>
  <last_update_submitted_qc>February 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Multiple Sclerosis, Relapsing-Remitting</mesh_term>
    <mesh_term>Multiple Sclerosis, Chronic Progressive</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ixazomib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03783416
org study id: 012436
secondary id: 2018-003686-34
nct id: NCT03783416
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study seeks to investigate safety and efficacy of ixazomib (NINLARO), a proteasome
      inhibitor, in multiple sclerosis (MS). Participants will receive either ixazomib capsules or
      placebo capsules for up to 24 months.
The production of antibodies in the form of oligoclonal bands (OCBs) from plasma cells (cells
      involved in the body's immune response), is the hallmark of MS. Recent evidence suggests that
      plasma cells are resident in the meninges (protective membranes of the brain and spinal cord)
      of people with Multiple Sclerosis (pwMS). Ixazomib is a drug which has been effective in
      treating multiple myeloma, a disease caused by aberrant plasma cells. The purpose of this
      study is to investigate whether ixazomib can reduce or clear OCBs from the cerebrospinal
      fluid (CSF) of pwMS. Participants will be randomly assigned to receive either ixazomib
      capsules (active drug arm) or placebo capsules (placebo arm) for up to 24 months.
      Participants with relapsing remitting MS (who are stable on disease modifying therapy) and
      those with progressive MS (who are not on disease modifying therapy) will be invited to take
      part in the study.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a double-blind, randomised, placebo-controlled trial. Randomisation will be stratified by disease stage, i.e. RRMS (and established on DMT) versus progressive MS (and not on DMT). The expected study duration is 36 months (a 12-month recruitment period and a 24-month treatment period). There will be 72 participants: 48 on ixazomib; 24 on placebo.
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Safety - Adverse events (AE) will be compared between active and placebo arm
time frame: Baseline to 24 months
description: Proportion of AEs in the Ixazomib versus placebo arm in subjects with Relapsing Remitting Multiple Sclerosis (RRMS)
Proportion of serious AEs (SAEs) in the Ixazomib versus placebo arm in subjects with RRMS
Proportion of AEs in the Ixazomib versus placebo arm in subjects with progressive MS
Proportion of serious AEs (SAEs) in the Ixazomib versus placebo arm in subjects with progressive MS
Proportion of AEs in the Ixazomib versus placebo arm in all subjects (subjects with RRMS and subjects with progressive MS)
Proportion of serious AEs (SAEs) in the Ixazomib versus placebo arm in all subjects (subjects with RRMS and subjects with progressive MS)
measure: Efficacy - the proportion of OCB IgG negative subjects will be compared between active and placebo arm
time frame: Baseline to 24 months
description: Proportion of all subjects (Relapsing Remitting Multiple Sclerosis and progressive Multiple Sclerosis subjects) negative for Oligoclonal Bands Immunoglobulin G (OCB IgG) antibodies measured in Cerebrospinal Fluid (CSF) in the Ixazomib versus placebo arm at 24 months
Proportion of subjects negative for Oligoclonal Bands Immunoglobulin G (OCB IgG) antibodies measured in Cerebrospinal Fluid (CSF) in the Ixazomib versus placebo arm at 24 months in subjects with Relapsing Remitting Multiple Sclerosis (RRMS)
Proportion of subjects negative for Oligoclonal Bands Immunoglobulin G (OCB IgG) antibodies measured in Cerebrospinal Fluid (CSF) in the Ixazomib versus placebo arm at 24 months in subjects with progressive Multiple Sclerosis
measure: Magnetic Resonance Imaging (MRI)
time frame: Baseline to 24 months
description: Change in T2 lesion load and gadolinium enhancing lesions on brain MRI with Ixazomib versus placebo arm at 24 months
measure: Change In Expanded Disability Status Scale (EDSS) with Ixazomib versus placebo arm at 24 months. The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist
time frame: Baseline to 24 months
description: Change in EDSS with ixazomib versus placebo at 24 months.
measure: Exploratory endpoint - IgG FLC
time frame: Baseline to 24 months
description: a. Proportion of all subjects who show reduction in total levels of Immunoglobulin G Free Light Chain (IgG FLC) in Cerebrospinal Fluid (CSF) at 24 months in the Ixazomib versus placebo arm.
measure: Exploratory endpoint - CD19
time frame: Baseline to 24 months
description: b. Proportion of all subjects who show change in levels of Cluster of Differentiation antigen 19 (CD 19) at 24 months in the Ixazomib versus placebo arm.
measure: Exploratory endpoint - soluble CD 138
time frame: Baseline to 24 months
description: c. Proportion of all subjects who show change in levels of soluble CD 138 at 24 months in the Ixazomib versus placebo arm
measure: Exploratory endpoint - CD 27
time frame: Baseline to 24 months
description: d. Proportion of all subjects who show change in levels of soluble CD 27 at 24 months in the Ixazomib versus placebo arm
measure: Exploratory endpoint - neurofilament light chain
time frame: Baseline to 24 months
description: e. Proportion of all subjects who show change in levels of neurofilament light chain at 24 months in the Ixazomib versus placebo arm
measure: Exploratory endpoint - neurofilament heavy chain
time frame: Baseline to 24 months
description: f. Proportion of all subjects who show change in levels of neurofilament heavy chain at 24 months in the Ixazomib versus placebo arm
measure: Exploratory endpoint - neopterin
time frame: Baseline to 24 months
description: g. Proportion of all subjects who show change in levels of neopterin at 24 months in the Ixazomib versus placebo arm
measure: Exploratory endpoint - cytokines profile
time frame: Baseline to 24 months
description: h. Proportion of all subjects who show change in levels of cytokines profile at 24 months in the Ixazomib versus placebo arm
measure: Exploratory endpoint - GFAP
time frame: Baseline to 24 months
description: i. Proportion of all subjects who show change in levels of Glial fibrillary acidic protein (GFAP) at 24 months in the Ixazomib versus placebo arm
measure: Exploratory endpoint - NCAM
time frame: Baseline to 24 months
description: j. Proportion of all subjects who show change in levels of Neural cell adhesion molecule (NCAM) at 24 months in the Ixazomib versus placebo arm
measure: Exploratory endpoint - GAP43
time frame: Baseline to 24 months
description: k. Proportion of all subjects who show change in levels of Growth Associated Protein 43 (GAP43) at 24 months in the Ixazomib versus placebo arm
measure: Exploratory endpoint - S100B
time frame: Baseline to 24 months
description: l. Proportion of all subjects who show change in levels of S100 calcium-binding protein B (S100B) at 24 months in the Ixazomib versus placebo arm
arm group label: Ixazomib (NINLARO®)
arm group type: Experimental
description: Treatment will follow a 28-day cycle. Participants will take one Ixazomib (NINLARO) capsule orally on days 1, 8, and 15 of each 28-day cycle, followed by one treatment-free week, in sequence, for the duration of the trial.
arm group label: Placebo
arm group type: Placebo Comparator
description: Treatment will follow a 28-day cycle. Participants will take one placebo capsule orally on days 1, 8, and 15 of each 28-day cycle, followed by one treatment-free, in sequence, for the duration of the trial.
intervention type: Drug
intervention name: Ixazomib (NINLARO®) capsules / Matching placebo capsules
description: Participants will be treated for a maximum of 24 months
arm group label: Ixazomib (NINLARO®)
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Multiple Sclerosis, Relapsing-Remitting
mesh term: Multiple Sclerosis, Chronic Progressive
mesh term: Sclerosis
mesh term: Ixazomib
sharing ipd: No