Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

MRI Trial to exPlore the efficAcy and Safety of IMU-838 in Relapsing Remitting Multiple Sclerosis (EMPhASIS) (EMPhASIS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03846219
Recruitment Status : Recruiting
First Posted : February 19, 2019
Last Update Posted : February 19, 2019
Sponsor:
Information provided by (Responsible Party):
Immunic AG

Brief Summary:

This is a Phase 2 multicenter, double-blind, placebo-controlled, randomized, parallel-group trial to assess the efficacy and safety of 2 once-daily oral doses of IMU-838 (vidofludimus calcium), a small molecule inhibitor of dihydroorotate dehydrogenase (DHODH), 30 mg/day and 45 mg/day, in patients with RRMS and evidence of active disease.

The trial consists of a screening period, a blinded 24-week main treatment period, and an optional initially blinded, then open-label extended treatment period of up to 9.5 years.

About 40 centers are planned to participate in Romania, Bulgaria, Ukraine, and Poland; potential additional centers in Hungary and Croatia. In total, 195 patients are planned to be randomized 1:1:1 to treatment with 30 mg/day or 45 mg/day IMU-838, or placebo (65 patients each) in the main treatment period. During the extended treatment period, patients will be re-randomized such that patients previously on placebo will be re-randomized 1:1 to treatment with 30 g/day or 45 mg/day IMU-838, all other patients will be re-randomized to the same treatment they previously received.


Condition or disease Intervention/treatment Phase
Relapsing-Remitting Multiple Sclerosis (RRMS) Drug: IMU-838 (30 mg/day) Drug: IMU-838 (45 mg/day) Drug: Placebo Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 195 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a Phase 2 multicenter, double-blind, placebo-controlled, randomized, parallel-group trial to assess the efficacy and safety of 2 once-daily oral doses of IMU-838 (30 mg/day and 45 mg/day) in patients with RRMS and evidence of active disease. The trial consists of a screening period, a blinded 24-week main treatment period, and an optional initially blinded, then open-label extended treatment period of up to 9.5 years.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Trial participants, treating and evaluating physicians, central MRI readers and all other personnel directly involved in the conduct of the trial will be blinded to treatment assignments during the main treatment period and for the initial time of the extended treatment period. The evaluating physician will also be blinded to any clinical outcome or treatment change.

Once the results of the main treatment period are available, treating physicians, participants, and other involved personnel, except for the evaluating physician, will be unblinded. The evaluating physician will remain blinded to patients' clinical characteristics and treatment assignment during the entire clinical trial.

Primary Purpose: Treatment
Official Title: Randomized, Double-blind, Placebo-controlled, Multicenter Phase 2 Trial Assessing the Effect of IMU-838 on Disease Activity, as Measured by Magnetic Resonance Imaging (MRI), as Well as Safety and Tolerability in Patients With Relapsing-remitting Multiple Sclerosis (RRMS)
Actual Study Start Date : January 28, 2019
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : June 2030

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: IMU-838 (30 mg/day)

Tablet containing 15 mg Vidofludimus calcium (IM90838). Once-daily oral dose of 30 mg consists of 2 tablets.

Duration: until the end of the main treatment period (24 weeks) and, optionally, during the extended treatment period (up to 9.5 years).

Drug: IMU-838 (30 mg/day)
  • Main treatment period: All patients will receive half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then start taking the full assigned dose from Day 7 onwards (2 tablets once daily).
  • Extended treatment period (optional): patients will receive 30 mg/day IMU-838 for up to 9.5 years. Patients on active treatment during the main treatment period will be randomized to continue their previous treatment assignment. Identical to the start of the main treatment period, all patients will receive half the assigned dose during the first 7 days of the extended treatment period and will then continue with the full assigned dose.

Once the results of the main treatment period are available, investigators and patients currently in the extended treatment period will be unblinded and investigators may then recommend switching the dose to a more effective dose or to an equally effective dose but with a lower risk for adverse events.

Other Name: Vidofludimus Calcium, Oral Tablet (30 mg/day)

Experimental: IMU-838 (45 mg/day)

Tablet containing 22.5 mg Vidofludimus calcium (IM90838). Once-daily oral dose of 45 mg consists of 2 tablets.

Duration: until the end of the main treatment period (24 weeks) and, optionally, during the extended treatment period (up to 9.5 years).

Drug: IMU-838 (45 mg/day)
  • Main treatment period: All patients will receive half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then start taking the full assigned dose from Day 7 onwards (2 tablets once daily).
  • Extended treatment period (optional): patients will receive 45 mg/day IMU-838 for up to 9.5 years. Patients on active treatment during the main treatment period will be randomized to continue their previous treatment assignment. Identical to the start of the main treatment period, all patients will receive half the assigned dose during the first 7 days of the extended treatment period and will then continue with the full assigned dose.

Once the results of the main treatment period are available, investigators and patients currently in the extended treatment period will be unblinded and investigators may then recommend switching the dose to a more effective dose or to an equally effective dose but with a lower risk for adverse events.

Other Name: Vidofludimus Calcium, Oral Tablet (45 mg/day)

Placebo Comparator: Placebo

Tablet containing no active ingredient. The placebo tablets will be identical to the IMU-838 tablets in terms of appearance, constitution of inactive ingredients, and packaging. Once-daily oral dose consists of 2 active compound-free tablets.

Duration: until the end of the main treatment period (24 weeks). For the optional extended treatment period, patients receiving placebo during the main treatment period will be randomized to 30 or 45 mg/day IMU-838.

Drug: Placebo
  • Main treatment period: All patients will receive 1 tablet per day during the first 7 days of the main treatment period and then start taking 2 tablets once daily from Day 7 onwards.
  • Extended treatment period (optional): Patients receiving placebo during the main treatment period will be randomized to 30 or 45 mg/day IMU-838. Identical to the start of the main treatment period, all patients will receive half the assigned dose during the first 7 days of the extended treatment period and will then continue with the full assigned dose.

Once the results of the main treatment period are available, investigators and patients currently in the extended treatment period will be unblinded and investigators may then recommend switching the dose to a more effective dose or to an equally effective dose but with a lower risk for adverse events.





Primary Outcome Measures :
  1. Difference between 45 mg/day IMU-838 and placebo in the cumulative number of combined unique active (CUA) MRI lesions [ Time Frame: Up to Week 24 ]
    Efficacy Endpoint

  2. Difference between 30 mg/day IMU-838 and placebo in the cumulative number of combined unique active (CUA) MRI lesions [ Time Frame: Up to Week 24 ]
    Efficacy Endpoint; Key secondary (hierarchical testing to primary efficacy)


Secondary Outcome Measures :
  1. Difference between 45 mg/day IMU-838 and 30 mg/day IMU-838 in the cumulative number of combined unique active (CUA) MRI lesions [ Time Frame: At Week 24 ]
    Efficacy Endpoint

  2. Difference between 30 mg/day IMU-838 and placebo, 45 mg/day IMU-838 and placebo, and 30 mg/day and 45 mg/day IMU-838 for the Mean number of CUA lesions per patient per scan at Weeks 6, 12, 18 and 24 [ Time Frame: Throughout the main treatment period (Day 0 - Week 24) ]

    MRI parameter

    Efficacy Endpoint


  3. Difference between 30 mg/day IMU-838 and placebo, 45 mg/day IMU-838 and placebo, and 30 mg/day and 45 mg/day IMU-838 for the Cumulative number of CUA MRI lesions up to Weeks 6, 12, and 18 [ Time Frame: Throughout the main treatment period (Day 0 - Week 24) ]

    MRI parameter

    Efficacy Endpoint


  4. Difference between 30 mg/day IMU-838 and placebo, 45 mg/day IMU-838 and placebo, and 30 mg/day and 45 mg/day IMU-838 for the Volume changes of T2 lesions at Weeks 6, 12, 18 and 24 compared to Baseline [ Time Frame: Throughout the main treatment period (Day 0 - Week 24) ]

    MRI parameter

    Efficacy Endpoint


  5. Difference between 30 mg/day IMU-838 and placebo, 45 mg/day IMU-838 and placebo, and 30 mg/day and 45 mg/day IMU-838 for the T2-lesion load at Weeks 6, 12, 18 and 24 compared to Baseline [ Time Frame: Throughout the main treatment period (Day 0 - Week 24) ]

    MRI parameter

    Efficacy Endpoint


  6. Difference between 30 mg/day IMU-838 and placebo, 45 mg/day IMU-838 and placebo, and 30 mg/day and 45 mg/day IMU-838 for the T1-lesion load at Weeks 6, 12, 18 and 24 compared to Baseline [ Time Frame: Throughout the main treatment period (Day 0 - Week 24) ]

    MRI parameter

    Efficacy Endpoint


  7. Difference between 30 mg/day IMU-838 and placebo, 45 mg/day IMU-838 and placebo, and 30 mg/day and 45 mg/day IMU-838 for the Cumulative number of new Gd+ lesions up to Weeks 6, 12, 18 and 24 [ Time Frame: Throughout the main treatment period (Day 0 - Week 24) ]

    MRI parameter

    Efficacy Endpoint


  8. Difference between 30 mg/day IMU-838 and placebo, 45 mg/day IMU-838 and placebo, and 30 mg/day and 45 mg/day IMU-838 for the Cumulative number of new T2 lesions up to Weeks 6, 12, 18 and 24 [ Time Frame: Throughout the main treatment period (Day 0 - Week 24) ]

    MRI parameter

    Efficacy Endpoint


  9. Difference between 30 mg/day IMU-838 and placebo, 45 mg/day IMU-838 and placebo, and 30 mg/day and 45 mg/day IMU-838 for the Cumulative number of new T1 lesions up to Weeks 6, 12, 18 and 24 [ Time Frame: Throughout the main treatment period (Day 0 - Week 24) ]

    MRI parameter

    Efficacy Endpoint


  10. Difference between 30 mg/day IMU-838 and placebo, 45 mg/day IMU-838 and placebo, and 30 mg/day and 45 mg/day IMU-838 for the Proportion of patients without new Gd+ lesions over 24 weeks [ Time Frame: Throughout the main treatment period (Day 0 - Week 24) ]

    MRI parameter

    Efficacy Endpoint


  11. Difference between 30 mg/day IMU-838 and placebo, 45 mg/day IMU-838 and placebo, and 30 mg/day and 45 mg/day IMU-838 for the Proportion of patients without new or enlarging T2-weighted lesions over 24 weeks [ Time Frame: Throughout the main treatment period (Day 0 - Week 24) ]

    MRI parameter

    Efficacy Endpoint


  12. Difference between 30 mg/day IMU-838 and placebo, 45 mg/day IMU-838 and placebo, and 30 mg/day and 45 mg/day IMU-838 for the Proportion of patients with CUA lesions at Week 24 [ Time Frame: Throughout the main treatment period (Day 0 - Week 24) ]

    MRI parameter

    Efficacy Endpoint


  13. Difference between 30 mg/day IMU-838 and placebo, 45 mg/day IMU-838 and placebo, and 30 mg/day and 45 mg/day IMU-838 for the Proportion of patients with Gd+ lesions at Week 24 [ Time Frame: Throughout the main treatment period (Day 0 - Week 24) ]

    MRI parameter

    Efficacy Endpoint


  14. Difference between 30 mg/day IMU-838 and placebo, 45 mg/day IMU-838 and placebo, and 30 mg/day and 45 mg/day IMU-838 for the Proportion of patients with T2 lesions at Week 24 [ Time Frame: Throughout the main treatment period (Day 0 - Week 24) ]

    MRI parameter

    Efficacy Endpoint


  15. Differences between treatments in changes of disease activity as measured by the Mean annualized relapse rate [ Time Frame: Throughout the clinical trial, up to 10 years ]
    Efficacy Endpoint

  16. Differences between treatments in changes of disease activity as measured by the Mean change in the Expanded Disability Status Scale (EDSS) as compared to Baseline during the main and extended period (every 12 weeks starting at Week 12) [ Time Frame: Throughout the clinical trial, up to 10 years ]

    The EDSS is a widely used and validated instrument evaluating the functional systems of the CNS to describe disease progression and the efficacy of MS therapy. The composite rating system ranges from 0 (normal neurological status) to 10 (death due to MS) in 0.5-unit increments.

    Efficacy Endpoint


  17. Differences between treatments in changes of disease activity as measured by the Proportion of patients with EDSS progression during the main and extended period (every 12 weeks starting at Week 12, and cumulatively) [ Time Frame: Throughout the clinical trial, up to 10 years ]

    The EDSS is a widely used and validated instrument evaluating the functional systems of the CNS to describe disease progression and the efficacy of MS therapy. The composite rating system ranges from 0 (normal neurological status) to 10 (death due to MS) in 0.5-unit increments.

    Efficacy Endpoint


  18. Differences between treatments in changes of disease activity as measured by the Proportion of relapse-free patients at 12-week intervals [ Time Frame: Throughout the clinical trial, up to 10 years ]
    Efficacy Endpoint

  19. Correlation of MRI-based assessments with quartiles of IMU-838 trough levels [ Time Frame: At Week 6 and Week 24 ]
    Efficacy Endpoint

  20. Number of Participants with AEs [ Time Frame: Throughout the clinical trial, up to 10 years ]
    Safety Endpoint

  21. Number of Participants with serious AEs [ Time Frame: Throughout the clinical trial, up to 10 years ]
    Safety Endpoint

  22. Number of Participants with ClinicallySignificant Laboratory Abnormalities (as assessed by the investigator) [ Time Frame: Throughout the clinical trial, up to 10 years ]
    Safety Endpoint

  23. Number of Participants with AEs of special interest: Red blood cell urine positive, at least of moderate intensity [ Time Frame: Throughout the clinical trial, up to 10 years ]
    Safety Endpoint

  24. Number of Participants with AEs of special interest: Hematuria [ Time Frame: Throughout the clinical trial, up to 10 years ]
    Safety Endpoint

  25. Number of Participants with AEs of special interest: Retroperitoneal colicky pain with suspected or confirmed nephrolithiasis [ Time Frame: Throughout the clinical trial, up to 10 years ]
    Safety Endpoint

  26. Proportion of patients treated with 30 mg/day or 45 mg/day IMU-838 as compared to placebo who experienced at least one of the following AEs: [ Time Frame: Throughout the clinical trial, up to 10 years ]
    • Neutropenia
    • Lymphopenia
    • Diarrhea
    • Alopecia
    • Hemorrhage
    • Abnormalities in alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), and total bilirubin with both elevations ˃1.5 x ULN and ≥35% elevated compared to Baseline

    Safety Endpoint


  27. 12-lead electrocardiogram (ECG): heart rate [ Time Frame: Throughout the clinical trial, up to 10 years ]
    Safety Endpoint

  28. 12-lead electrocardiogram (ECG): PQ-interval [ Time Frame: Throughout the clinical trial, up to 10 years ]
    Safety Endpoint

  29. 12-lead electrocardiogram (ECG): QRS-interval [ Time Frame: Throughout the clinical trial, up to 10 years ]
    Safety Endpoint

  30. 12-lead electrocardiogram (ECG): QT-interval [ Time Frame: Throughout the clinical trial, up to 10 years ]
    Safety Endpoint

  31. 12-lead electrocardiogram (ECG): heart rate-corrected QTc interval (according to Bazett's formula) [ Time Frame: Throughout the clinical trial, up to 10 years ]
    Safety Endpoint

  32. Physical examination [ Time Frame: Throughout the clinical trial, up to 10 years ]

    Physical examinations will cover the following body systems: general appearance, skin, neck (including thyroid), throat, lungs, heart, abdomen, back, lymph nodes, extremities, vascular, neurological systems, and, if applicable, others. Any new clinically significant finding compared to Screening Visit 1 must be documented as AE. Any clinically significant finding at Screening Visit 1 must be documented in the medical history section of the eCRF.

    Safety Endpoint


  33. Vital signs: height [ Time Frame: at Screening ]

    Height in centimeters will be recorded without shoes. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

    Safety Endpoint


  34. Vital signs: weight [ Time Frame: Throughout the clinical trial, up to 10 years ]

    Weight in kilograms will be recorded without shoes. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

    Safety Endpoint


  35. Vital signs: body temperature (ºC) [ Time Frame: Throughout the clinical trial, up to 10 years ]

    Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

    Safety Endpoint


  36. Vital signs: respiratory rate [ Time Frame: Throughout the clinical trial, up to 10 years ]

    Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

    Safety Endpoint


  37. Vital signs: pulse rates [ Time Frame: Throughout the clinical trial, up to 10 years ]

    Pulse must be measured with the patient in a seated position, after at least 5 minutes at rest.

    Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

    Safety Endpoint


  38. Vital signs: systolic and diastolic blood pressures [ Time Frame: Throughout the clinical trial, up to 10 years ]

    Blood pressure (systolic and diastolic) must be measured with the patient in a seated position, after at least 5 minutes at rest.

    Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

    Safety Endpoint


  39. Micro ribonucleic acid-122 expression [ Time Frame: Change from Baseline to 4 hours after first dose ]
    Safety Endpoint

  40. Presence of John Cunningham virus (JCV) deoxyribonucleic acid (DNA) in urine in patients with detectable JCV-DNA in urine [ Time Frame: At Screening Visit 1, at Week 24, and at end of study visit (EoS visit 30 days (+14 days) after last IMP intake) ]
    Safety Endpoint

  41. Population Pharmacokinetics: minimum IMU-838 plasma concentration over the dosing interval (Cmin) [ Time Frame: At Week 6 (3-10 hours post-dose) ]
    One single measurement between 3 and 10 hours post-dose Pharmacokinetics

  42. Population Pharmacokinetics: maximum IMU-838 plasma concentration over the dosing interval (Cmax) [ Time Frame: At Week 6 (3-10 hours post-dose) ]
    One single measurement between 3 and 10 hours post-dose Pharmacokinetics

  43. Population Pharmacokinetics: area under the IMU-838 plasma concentration-time curve over the dosing interval (AUC0-τ) [ Time Frame: At Week 6 (3-10 hours post-dose) ]
    One single measurement between 3 and 10 hours post-dose Pharmacokinetics

  44. Population Pharmacokinetics: IMU-838 apparent clearance following oral dosing (CL/F) [ Time Frame: At Week 6 (3-10 hours post-dose) ]
    One single measurement between 3 and 10 hours post-dose Pharmacokinetics

  45. Population Pharmacokinetics: IMU-838 apparent volume of distribution (V/F) [ Time Frame: At Week 6 (3-10 hours post-dose) ]
    One single measurement between 3 and 10 hours post-dose Pharmacokinetics

  46. Plasma trough levels of IMU-838 [ Time Frame: At Days 7 and Weeks 6, 12, 18, and 24 ]
    Pharmacokinetics

  47. Changes from Baseline in Th1 lymphocyte subset as measured by flow cytometry [ Time Frame: At Weeks 6 and 24 (in selected Biomarker Centers only) ]
    Pharmacodynamics

  48. Changes from Baseline in Th17 lymphocyte subset as measured by flow cytometry [ Time Frame: At Weeks 6 and 24 (in selected Biomarker Centers only) ]
    Pharmacodynamics

  49. Changes from Baseline in Treg lymphocyte subset as measured by flow cytometry [ Time Frame: At Weeks 6 and 24 (in selected Biomarker Centers only) ]
    Pharmacodynamics

  50. Changes from Baseline in serum neurofilament [ Time Frame: At Week 24 ]
    Pharmacodynamics

  51. Treatment Satisfaction Questionnaire for Medication (TSQM) [ Time Frame: At Week 6, Week 24 and end of study visit (EoS visit 30 days (+14 days) after last IMP intake) ]

    The TSQM is a reliable and valid instrument to assess patients' satisfaction with medication, providing scores on 4 scales: side effects, performance, convenience and global satisfaction.

    Scale values include (listed from worst to best outcome):

    1. Extremely Dissatisfied,
    2. Very Dissatisfied,
    3. Dissatisfied,
    4. Somewhat Satisfied,
    5. Satisfied,
    6. Very Satisfied,
    7. Extremely Satisfied

    Health outcome




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria for the main treatment period

  1. Male or female patient (age ≥18 to 55 years, inclusive)
  2. Diagnosis of RRMS according to the revised McDonald criteria (2017) Note: The diagnosis of MS (including "dissemination in time") must have been established before the patient is screened for the trial.
  3. Disease activity evidenced

    • by either at least 2 relapses in the last 24 months, or at least 1 relapse in the last 12 months before randomization (relapses must have been assessed and documented by a physician in the patient files), AND
    • ≥1 documented Gd+ MS-related brain lesion, in the last 6 months before informed consent (date of MRI examination as well as copy of MRI report or representative image has to be available and accessible as patient source data at the study site)
  4. Expanded Disability Status Scale (EDSS) score between 0 and 4.0 (inclusive) at Screening Visit 1
  5. Female patients

    • must be of non-child-bearing potential i.e. surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before Screening Visit 1) or post menopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause), or
    • if of child-bearing potential, must have a negative pregnancy test at Screening Visit 1 (blood test) and before the first IMP intake (Day 0 urine test). They must agree not to attempt to become pregnant, must not donate ova, and must use a highly effective contraceptive method (see below) together with a barrier method between trial consent and 30 days after the last intake of the of the IMP.

    Highly effective forms of birth control are those with a failure rate less than 1% per year and include:

    • oral, intravaginal, or transdermal combined (estrogen and progestogen containing) hormonal contraceptives associated with inhibition of ovulation
    • oral, injectable, or implantable progestogen-only hormonal contraceptives associated with inhibition of ovulation
    • intrauterine device or intrauterine hormone-releasing system
    • bilateral tubal occlusion
    • vasectomized partner (i.e. the patient's male partner underwent effective surgical sterilization before the female patient entered the clinical trial and is the sole sexual partner of the female patient during the clinical trial)
    • sexual abstinence (acceptable only if it is the patient's usual form of birth control/lifestyle choice; periodic abstinence [e.g. calendar, ovulation, symptothermal, postovulation methods] and withdrawal are no acceptable methods of contraception)

    Barrier methods of contraception include:

    • Condom (without spermicidal foam/gel/film/cream/suppository or fat- or oil-containing lubricants)
    • Occlusive cap (diaphragm or cervical/vault caps) with spermicidal gel/film/cream/suppository
  6. Male patients must agree not to father a child or to donate sperm starting at Screening Visit 1, throughout the clinical trial and for 30 days after the last intake of the IMP. Male patients must also

    • abstain from sexual intercourse with a female partner (acceptable only if it is the patient's usual form of birth control/lifestyle choice), or
    • use adequate barrier contraception during treatment with the IMP and until at least 30 days after the last intake of the IMP, and
    • if they have a female partner of childbearing potential, the partner should use a highly effective contraceptive method as outlined in inclusion criterion 5
    • if they have a pregnant partner, they must use condoms while taking the IMP to avoid exposure of the fetus to the IMP
  7. Willingness and ability to comply with the protocol
  8. Written informed consent given prior to any trial-related procedure

Inclusion criteria for optional extended treatment period

  1. 24 weeks of main treatment
  2. Valid baseline MRI and Week 24 MRI, as well as 2 additional post-dose MRIs

Exclusion criteria

MS-related exclusion criteria

  1. Any disease other than MS that may better explain the signs and symptoms, including history of complete transverse myelitis
  2. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from these
  3. Clinical signs or presence of laboratory findings suggestive for neuromyelitis optica (NMO) spectrum disorders or MOG-IgG-associated encephalomyelitis (i.e. presence of anti-NMO [acquaporin-4] antibodies or anti-MOG-antibodies)
  4. MS types other than RRMS
  5. Any MRI finding, atypical for MS, including but not limited to a longitudinally extensive spinal cord lesion
  6. Any active and uncontrolled coexisting autoimmune disease, other than MS (except for type 1 diabetes mellitus and inflammatory bowel disease)
  7. An MS relapse within 30 days before Screening Visit 1 and/or during the screening period (until Day 0)

    Therapy exclusion criteria

  8. Any previous or current use of the following MS treatments: monoclonal antibodies (natalizumab, alemtuzumab, daclizumab, ocrelizumab, anti-CD4, rituximab or belimumab, including their biosimilars), total lymphoid irradiation, bone marrow transplantation, stem cell transplantation, or any use of DHODH inhibitors, including teriflunomide (Aubagio™) or leflunomide (Arava™)
  9. Any use of the following MS treatments within 12 months before the date of informed consent: any cytokine (other than interferon) or anti-cytokine therapy, intravenous immunoglobulin, mitoxantrone, cytotoxic or immunosuppressive therapy (including, but not limited to azathioprine and cyclophosphamide, excluding only systemic steroids or adrenocorticotrophic hormone [ACTH]), tofacitinib, methotrexate, mycophenolate mofetil, mycophenolate sodium, fingolimod, any calcineurin inhibitors (e.g. tacrolimus, cyclosporine, or pimecrolimus)
  10. Any use of the following MS treatments within 30 days before the date of informed consent: interferon-β, glatiramer acetate, dimethyl fumarate and plasmapheresis
  11. Within 30 days before the baseline MRI: Use of systemic corticosteroids (intravenous or oral) or ACTH
  12. Use of the following concomitant medications is prohibited at Screening Visit 1 and throughout the duration of the trial:

    • any medication known to significantly increase urinary elimination of uric acid, in particular lesinurad (Zurampic™) as well as uricosuric drugs such as probenecid
    • treatments for any malignancy, in particular irinotecan, paclitaxel, tretinoin, bosutinib, sorafinib, enasidenib, erlotinib, regorafenib, pazopanib and nilotinib
    • any drug significantly restricting water diuresis, in particular vasopressin and vasopressin analogs
    • use of rosuvastatin at daily doses higher than 10 mg
  13. Use of any investigational product within 8 weeks or 5 x the respective half-life before the date of informed consent, whichever is longer, and throughout the duration of the trial

    Immune response exclusion criteria

  14. Conditions negatively affecting the immune response such as previous organ transplant
  15. Clinically significantly low lymphocyte and/or neutrophil count (Common Terminology Criteria for AEs Grade of 2 or higher), i.e.

    • lymphocyte count <800/mm³ (0.8 x 109/L), and/or
    • neutrophil count <1,500/mm³ (1.5 x 109/L)
  16. History of chronic systemic infections within 6 months before the date of informed consent, including but not limited to tuberculosis, human immunodeficiency virus (HIV), hepatitis B or C
  17. Positive IFNγ release assay for Mycobacterium tuberculosis at Screening Visit 1
  18. Positive hepatitis B virus surface antigen (HBsAg), hepatitis B core antibody (HBcAb), positive HCV and/or HIV-antigen-antibody test at Screening Visit 1
  19. Any live vaccinations within 30 days before the date of informed consent except for the influenza vaccine Other medical history and concomitant disease exclusion criteria
  20. Presence of the following laboratory values at Screening Visit 1:

    • platelet count <100,000/mm³ (<100 109/L)
    • serum creatinine >1.5 x ULN
    • total bilirubin, ALT, or GGT >1.5 x ULN
    • Serum uric acid levels at Screening Visit 1 >1.2 x ULN (for women >6.8 mg/dL, for men >8.4 mg/dL)
    • indirect (unconjugated) bilirubin >1.2 x ULN (i.e. >1.1 mg/dL)
  21. Known history of nephrolithiasis or underlying condition with a strong association of nephrolithiasis, including hereditary hyperoxaluria or hereditary hyperuricemia
  22. History or clinical diagnosis of gout
  23. Renal impairment defined as estimated glomerular filtration rate ≤60 mL/min/1.73m²
  24. Known or suspected Gilbert syndrome
  25. Diagnosis or suspected liver function impairment which may cause fluctuating liver function tests during this trial, as assessed by the investigator
  26. History or presence of serious or acute heart disease such as uncontrolled cardiac dysrhythmia or arrhythmia, uncontrolled angina pectoris, cardiomyopathy, or uncontrolled congestive heart failure (New York Heart Association [NYHA] class 3 or 4) Note: NYHA class 3: Cardiac disease resulting in marked limitation of physical activity. Patients are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, or anginal pain. NYHA class 4: Cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.
  27. Clinically relevant, severe pulmonary diseases, uncontrolled hypertension, or poorly controlled diabetes
  28. Concurrent malignancy or prior malignancy within the previous 10 years except for the following: adequately-treated non-melanoma skin cancer and adequately-treated cervical cancer
  29. History or presence of any major medical or psychiatric illness (such as severe depression, psychosis, bipolar disorder), history of suicide attempt, or current suicidal ideation that in the opinion of the investigator could create undue risk to the patient or could affect adherence with the trial protocol
  30. Epilepsy or seizures not adequately controlled by treatment
  31. Any other substantial medical condition that in the opinion of the investigator could create undue risk to the patient or could affect adherence with the trial protocol

    General exclusion criteria

  32. Current or past (within 12 months of Screening Visit 1) alcohol or drug abuse
  33. Any condition that would prevent the patient from undergoing an MRI scan, including:

    • claustrophobic conditions
    • unable to receive Gd-based MRI-contrast agents due to history of hypersensitivity to Gd based contrast agents, or severe renal insufficiency
    • presence of metallic implants incompatible with brain MRI
  34. Legal incapacity, limited legal capacity, or any other condition that makes the patient unable to understand the patient information and informed consent form
  35. Pregnant or breastfeeding
  36. An employee of an investigator or sponsor or an immediate relative of an investigator
  37. Patients institutionalized due to judicial or administrative order

Exclusion criteria for optional extended treatment period

  1. Any ongoing, clinically significant (as assessed by the investigator) treatment-emergent (started after intake of IMP) AE or laboratory abnormality (including blood chemistry and urinalysis)
  2. Significant treatment or trial non-compliance during the main treatment period (as assessed by the investigator), and/or inability or unwillingness to follow instructions by trial personnel
  3. Treatment compliance <70% during the main treatment period
  4. Significant protocol deviations during the main treatment period that are assessed by the investigator to negatively affect further patient cooperation in this trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03846219


Contacts
Layout table for location contacts
Contact: Andreas Muehler +49 89 2500 794 64 andreas.muehler@immunic.de

Locations
Layout table for location information
Bulgaria
UMHAT "Dr.Georgi Stranski" EAD Pleven Department of Professional Diseases Recruiting
Pleven, Bulgaria, 5800
Contact: Maya Danovska, Assoc. Prof.         
UMHAT"Dr. Georgi Stranski" EAD, Clinic of Neurology Diseases Recruiting
Pleven, Bulgaria, 5800
Contact: Plamen Bozhinov, Prof.         
UMHAT "Sveti Ivan Rilski" EAD Sofia Clinic of Neurological Diseases Recruiting
Sofia, Bulgaria, 1431
Contact: Penko Shotekov, Prof.         
Sponsors and Collaborators
Immunic AG
Investigators
Layout table for investigator information
Study Director: Andreas Muehler Immunic AG

Layout table for additonal information
Responsible Party: Immunic AG
ClinicalTrials.gov Identifier: NCT03846219     History of Changes
Other Study ID Numbers: P2-IMU-838-MS
2018-001896-19 ( EudraCT Number )
First Posted: February 19, 2019    Key Record Dates
Last Update Posted: February 19, 2019
Last Verified: February 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Immunic AG:
RRMS
Multiple Sclerosis (MS)

Additional relevant MeSH terms:
Layout table for MeSH terms
Sclerosis
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Calcium
Calcium, Dietary
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Bone Density Conservation Agents