Relapsing Multiple Sclerosis active Relapsing Multiple Sclerosis (RMS)
Conditions
Interventions
Patients will be randomly assigned in a 1:1 ratio to receive either IMU-838 or placebo in a double-blind fashion. For the first week (Days 1 to 7), patients will take a 15 mg tablet of IMU 838 or plac
defined as confirmed relapse or confirmed disability progression during the double-blind treatment). Patients with a confirmed MSBE will be required to re-consent to one of the 3 study continuation op
Eligible patients will be randomized (1:1) in a blinded fashion to either placebo or IMU-838.
Treatment
Sponsors
Immunic AG
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: 1. Male or female patient (age =18 to =55 years). 2. Patients with an established diagnosis of MS according to 2017 McDonald Criteria . 3. Patients with RMS comprising of relapsing remitting MS (RRMS) and active secondary progressive MS, both defined according to Lublin criteria 1996 and 2014.a a Patients are eligible for this trial if their disease modifying treatment has failed due to efficacy, safety, or tolerability issues, if they have contraindications or no access to treatment, or if they refuse the offered MS treatment. 4. Active disease as defined by Lublin 2014 evidenced prior to Screening by: a. At least 2 relapsesa in the last 24 months before randomization, or b. At least 1 relapsea in the last 12 months before randomization , or c. A positive Gd+ MRI scan (brain and/or spine) in the last 12 months prior to randomization. aRelapses must have been assessed and documented by a physician in the patient files. 5. EDSS score between 0 and 5.5 (inclusive) at SV1. 6. Female patients: a. must be of non-childbearing potential, ie, surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before SV1) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause), or b. if of childbearing potential, must have a negative pregnancy test at SV1 (blood test) and before the first IMP intake (Day 1 blood or 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 study consent and 30 days after the last intake of the IMP. c. highly effective forms of birth control are those with a failure rate less than 1% per year and include: i. oral, intravaginal, or transdermal combined (estrogen and progestogen containing) hormonal contraceptives associated with inhibition of ovulation. ii. oral, injectable, or implantable progestogen-only hormonal contraceptives associated with inhibition of ovulation. iii. intrauterine device or intrauterine hormone-releasing system. iv. bilateral tubal occlusion. v. vasectomized partner (ie, the patient’s male partner underwent effective surgical sterilization before the female patient entered the clinical study and is the sole sexual partner of the female patient during the clinical study). vi. sexual abstinence (acceptable only if it is the patient’s usual form of birth control/lifestyle choice; periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception). d. Barrier methods of contraception include: i. condom. ii. occlusive cap (diaphragm or cervical/vault caps) with spermicidal gel/film/cream/suppository. 7. Male patients must agree not to father a child or to donate sperm starting at SV1, throughout the clinical study, and for 30 days after the last intake of the IMP. Male patients must also: a. abstain from sexual intercourse with a female partner (acceptable only if it is the patient’s usual form of birth control/lifestyle choice), or b. use adequate barrier contraception during treatment with the IMP and until at least 30 days after the last intake of the IMP, and c. if they have a female partner of childbearing potential, the partner should use a highly effective contraceptive method as outlined in inclusion criterion 5. d. if they have a pregnant partner, they must us
Exclusion criteria
Exclusion criteria: Exclusion Criteria for the Main Period of the Study Multiple sclerosis-related exclusion criteria: 1. Patients with non-active secondary progressive MS and primary progressive MS. 2. Any disease other than MS that may better explain the signs and symptoms, including history of complete transverse myelitis. 3. Clinical signs or presence of laboratory findings suggestive for neuromyelitis optica (NMO) spectrum disorders or myelin oligodendrocyte glycoprotein (MOG)-IgG-associated encephalomyelitis. 4. Any MRI finding, which puts in question the MS diagnosis, including but not limited to a longitudinally extensive spinal cord lesion. 5. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or adequately treated cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence full remission at the current time. 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 ending within 30 days before SV1 and/or during the Screening Period (until Day 1). 8. Any corticosteroid treatment for relapse given within 30 days before SV2. Therapy exclusion criteria: 9. Use of experimental/investigational drug (with the exception of COVID-19 vaccines approved by emergency use authorization) within 8 weeks or 5 times the respective half-life before the date of informed consent, whichever is longer, and throughout the duration of the study; and/or participation in drug clinical studies within 6 months prior to Screening (For selected approved marketed products, if used as an investigational drug, exclusion criterion 11 applies). 10. Any previous treatment with: a. total lymphoid irradiation b. bone marrow transplantation c. stem cell transplantation d. cladribine, alemtuzumab, or belimumab, including their biosimilars Lifelong: • cyclophosphamide • mitoxantrone, if cumulative life-time dose >60 mg/m² or if evidence of cardiotoxicity following mitoxantrone treatment Within 12 months: • any use of DHODH inhibitors, including teriflunomide or leflunomide • anti-CD 19/20 (ocrelizumab, rituximab, ofatumumab, including their biosimilars and investigational products) • mitoxantrone • daclizumab Within 6 months: • natalizumab • calcineurin inhibitors (eg, tacrolimus, cyclosporine, or pimecrolimus) • immunoglobulins • azathioprine Within 3 months: • plasmapheresis • any cytokine (other than interferon) or anti-cytokine therapy • methotrexate • Sphingosine-1-receptor (S1P) modulators (including, but not limited, fingolimod, siponimod, and ozanimod) • Tofactinib • mycophenolate mofetil or mycophenolate sodium • recurrent pulsed intravenous or intrathecal corticosteroid treatments. Within 30 days • dimethyl fumarate, monomethyl fumarate, and diroximel fumarate • slow-release (pegylated) forms of interferons or depot formulations of glatiramer acetate Within 7 days • interferon-ß • glatiramer acetate 12. Any use of adrenocorticotrophic hormone (ACTH) or occasional use of systemic corticosteroids (oral or intravenous) 30 days before SV2. 13. Any use of the following concomitant medications is prohibited during Screening and throughout the duration of the study: a. any medication known to significantly increase urinary elimination of uric acid, in particular lesinurad, as well as uricosuric drugs such as probene
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Name: The primary objective is to demonstrate the efficacy of IMU-838 versus placebo in adult patients with active RMS in delaying the occurrences of relapses based on time to first relapse (T2FR);Timepoints: Time to first confirmed relapse, as determined by the Independent Neurology Evaluation Committee (INEC), relapse occurred after the start of treatment administration and before the end of the main period (EOMP), censored at a maximum of 72 weeks, Visit 8 (V8)/EOMP;Measure: Hazard ratio (HR) for relapsefree survival between patients randomized to IMU-838 and placebo | — |
Secondary
| Measure | Time frame |
|---|---|
| Name: The secondary efficacy objective is to evaluate the effect of IMU-838 versus placebo on volume of new T2-lesions;Timepoints: Changes in total volume of new T2-lesions from baseline (BL, SV2) magnetic resonance imaging (MRI) until Week 24 MRI;Measure: Mean difference in the volume of new T2 lesions between IMU- 838- and placebo-treated patients, on a logarithmic scale;Name: The secondary efficacy objective is to evaluate the effect of IMU-838 versus placebo on disability progression;Timepoints: Time to 12-week confirmed disability worsening (12wCDW) as assessed on Expanded Disability Status Scale (EDSS); as defined in this protocol during the MP (censored until at Week 72/EOMP visit but with confirmation potentially done within EP, if applicable);Measure: HR for no worsening survival between IMU-838- and placebotreated patients;Name: The secondary efficacy objective is to evaluate the effect of IMU-838 versus placebo on cognitive performance;Timepoints: Time to confirmed clinically relevant changes in Symbol Digit Modalities Test (SDMT) in the MP (censored Week 72/EOMP);Measure: HR for no changes survival between IMU-838- and placebotreated patients;Name: The secondary efficacy objective is to the effect of IMU-838 versus placebo on whole brain atrophy;Timepoints: Annualized rate of percentage changes in whole brain volume from BL MRI to until V8/EOMP MRI;Measure: Difference in mean rate of the percentage change in whole brain volume between IMU-838- and placebo-treated patients | — |
Countries
Albania, Belarus, Bosnia and Herzegovina, Bulgaria, Colombia, Estonia, Georgia, Greece, India, Jordan, Latvia, Lebanon, Lithuania, Mexico, Peru, Poland, Republic of Moldova, Republic of Serbia, Romania, Russian Federation, South Africa, The Former Yugoslav Rep of Macedonia, Turkey, Ukraine, United Kingdom, United States of America
Contacts
Public ContactAziz Zoghbi
Director of Country Oversight and Manageme nt MENA, Gulf and Africa
Outcome results
None listed