relapsing-remitting multiple sclerosis MedDRA version: 21.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
Immunic AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 o 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 o =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 o 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 o 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 - 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 o abstain from sexual intercourse with a female partner (acceptable only if it is the patient’s usual form of birth control/lifestyle choice), or o use adequate barrier contraception during treatment with the IMP and until at least 30 days after the last intake of the IMP, and o if they have a female partner of childbearing potential, the partner should use a highly effective contraceptive method as outlined in inclusion criterion 5 o 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. Writ
Exclusion criteria
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-associated encephalomyelitis (i.e. presence of anti-NMO [aquaporin-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) 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: o claustrophobic conditions o unable to receive Gd-based MRI-contrast agents due to history of hypersensitivity to Gd-based contrast agents, or severe renal insufficiency o 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 a normality (including blood chemistry and urinalysis)7 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Cohort 1 (i.e. the main study): Primary • To evaluate the efficacy of 45 mg/day IMU-838 in the treatment of RRMS based on MRI assessments Cohort 2 (i.e. the sub-study): Primary • To obtain more efficacy and safety data of IMU-838 in patients with RRMS and to allow pharmacodynamic modelling of the dose response.;Secondary Objective: Secondary • To evaluate the efficacy of 30 mg/day IMU-838 in the treatment of RRMS based on magnetic resonance imaging (MRI) assessments • To evaluate the safety and tolerability of 30 mg/day and 45 mg/day IMU-838 in RRMS patients Tertiary • To evaluate PD effects of IMU-838 in RRMS patients • To evaluate IMU-838 trough values and population PK • To evaluate the effects of IMU-838 on treatment satisfaction in patients with RRMS;Primary end point(s): Efficacy Cohort 1 (C1): Difference between 45 mg/day IMU-838 and placebo in the cumulative number of combined unique active (CUA) MRI lesions up to Week 24 Cohort 2 (C2): Between-treatment differences in the cumulative number of CUA MRI and Gd+ lesions up to Week 24 ;Timepoint(s) of evaluation of this end point: Up to Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary (hierarchical testing to primary efficacy) Efficacy C1: Difference between 30 mg/day IMU-838 and placebo in the cumulative number of CUA MRI lesions up to Week 24 Secondary Efficacy • C1: Difference between 45 mg/day IMU-838 and 30 mg/day IMU-838 in the cumulative number of CUA MRI lesions at Week 24 • C1: 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 following MRI parameters and C2: Between-treatment differences in the following MRI parameters: o C1+C2: Mean number of CUA lesions per patient per scan at Weeks 6, 12, 18 and 24 o C1: Cumulative number of CUA MRI lesions up to Weeks 6, 12, and 18 o C2: Cumulative number of CUA MRI lesions up to Weeks 6, 12, 18, and 24 o C1: Volume changes of T2 lesions at Weeks 6, 12, 18 and 24 compared to Baseline o C1+C2: T2-lesion load at Weeks 6, 12, 18 and 24 compared to Baseline o C1+C2: T1-lesion load at Weeks 6, 12, 18 and 24 compared to Baseline o C1+C2: Cumulative number of new Gd+ lesions up to Weeks 6, 12, 18 and 24 o C1+C2: Cumulative number of new T2 lesions up to Weeks 6, 12, 18 and 24 o C1+C2: Cumulative number of new T1 lesions up to Weeks 6, 12, 18 and 24 o C1+C2: Proportion of patients without new Gd+ lesions over 24 weeks o C1+C2: Proportion of patients without new or enlarging T2-weighted lesions over 24 weeks o C1: Proportion of patients with CUA lesions at Week 24 o C1: Proportion of patients with Gd+ lesions at Week 24 o C1: Proportion of patients with T2 lesions at Week 24 • C1: Differences between individual treatments and between the pooled 30 mg/day and 45 mg/day groups and placebo in the following relapse-related clinical endpoints: o Mean annualized relapse rate (during main and extended treatment period) o Proportion of relapse-free patients up to Week 24 and at extended periods thereafter o Time to relapse at time of final analysis of main part • C2: Number of relapses in each tr | — |
Countries
Bulgaria, Germany, Poland, Romania, Ukraine
Contacts
Public ContactChief Medical Officer
Immunic AG
Outcome results
None listed