Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of Vidofludimus Calcium on MRI-Assessed Disease Activity in Relapsing-Remitting Multiple Sclerosis
- Trial ID
- 2024-516739-29-00
- Protocol
- P2-IMU-838-MS
- Sponsor
- Immunic AG
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 2 trial is to evaluate the **efficacy** of 45 mg/day IMU-838 in the treatment of **relapsing-remitting multiple sclerosis** (RRMS) based on magnetic resonance imaging (MRI) assessments. This is clinically relevant as MRI is a critical tool in assessing disease activity and progression in RRMS, providing insights into the potential therapeutic benefits of IMU-838. Additionally, the sub-study aims to obtain more efficacy and safety data of IMU-838 in patients with RRMS and to allow pharmacodynamic modeling of the dose response. This will contribute to understanding the optimal dosing and safety profile of IMU-838, which is essential for its potential use in clinical practice.
Participants
The clinical trial involves a total of **128 participants** diagnosed with **relapsing-remitting multiple sclerosis** (RRMS). The study population includes both male and female subjects, aged between 18 and 55 years. Participants were selected based on specific criteria, including a confirmed diagnosis of RRMS according to the revised McDonald criteria (2017) and documented disease activity. The general health status of participants is characterized by an Expanded Disability Status Scale (EDSS) score ranging from 0 to 4.0. Lifestyle considerations such as diet and physical activity are not specified, but participants must adhere to specific contraceptive measures if of childbearing potential. The trial does not provide additional information on the lifestyle or habits of the participants. The selection process ensures that the trial population is representative of individuals with RRMS, with a focus on obtaining efficacy and safety data for the investigational product, IMU-838.
Plans and Procedures
The clinical trial is a **randomized, double-blind, placebo-controlled** Phase 2 study designed to evaluate the efficacy and safety of **IMU-838** in patients with **relapsing-remitting multiple sclerosis** (RRMS). The trial aims to assess the effect of IMU-838 on disease activity, as measured by magnetic resonance imaging (MRI), over a period of 24 weeks. The study involves two cohorts: the main study cohort and a sub-study cohort, each with specific objectives related to efficacy and safety data collection. The trial is expected to conclude by December 31, 2029, with recruitment having commenced on February 1, 2019.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of RRMS, and disease activity. The main treatment period requires participants to have an Expanded Disability Status Scale (EDSS) score between 0 and 4.0. Female participants of child-bearing potential must adhere to strict contraceptive measures, while male participants must agree to avoid fathering a child during the trial. Following the screening, participants will be randomized to receive either IMU-838 or a placebo, administered orally in tablet form.
Study visits will occur at regular intervals to monitor safety and efficacy, with MRI assessments conducted to evaluate the primary endpoint of the cumulative number of combined unique active (CUA) MRI lesions. Secondary endpoints include differences in relapse rates and changes in EDSS scores. Participants will also be monitored for adverse events and laboratory abnormalities. The end-of-study visit will mark the completion of the 24-week treatment period, with an optional extended treatment period available for those meeting specific continuation criteria.
Participant involvement is expected to last for the duration of the 24-week treatment period, with the possibility of extension based on MRI results and other criteria. Conditions that may lead to early termination from the study include non-compliance with the protocol, significant adverse events, or withdrawal of consent. The trial's design ensures rigorous monitoring and data collection to achieve its objectives while maintaining participant safety and adherence to ethical standards.
Treatment
The clinical trial involves the administration of **IMU-838**, a chemically synthesized medication containing the active substance **vidofludimus calcium**. The pharmaceutical form of IMU-838 is a tablet, and it is available in three different dosages: 15 mg, 22.5 mg, and 30 mg. The tablets are administered orally. The maximum daily dose of IMU-838 is 45 mg, with a total maximum dose of 50 mg over a treatment period of up to 120 days. The medication is not formulated for pediatric use and is not classified as an orphan drug. The trial aims to evaluate the efficacy and safety of IMU-838 in patients with relapsing-remitting multiple sclerosis (RRMS), with a focus on disease activity as measured by magnetic resonance imaging (MRI).
A placebo is also utilized in this study as a comparator treatment. The placebo is designed to match the IMU-838 tablets in appearance but does not contain the active substance **vidofludimus calcium**. The placebo is administered in the same manner as the active treatment, ensuring that the study remains double-blind. This allows for an unbiased assessment of the efficacy and safety of IMU-838 by comparing it to the placebo group. The use of a placebo is critical in determining the true therapeutic effect of the experimental medication.
Efficacy
The efficacy of the investigational product, **vidofludimus calcium** (IMU-838), will be assessed in a Phase 2 clinical trial involving patients with relapsing-remitting multiple sclerosis (RRMS). The primary efficacy endpoint for Cohort 1 is the difference between 45 mg/day IMU-838 and placebo in the cumulative number of combined unique active (CUA) MRI lesions up to Week 24. For Cohort 2, the primary endpoint is the between-treatment differences in the cumulative number of CUA MRI and Gd+ lesions up to Week 24.
Secondary efficacy endpoints include the difference between 30 mg/day IMU-838 and placebo in the cumulative number of CUA MRI lesions up to Week 24, and the difference between 45 mg/day and 30 mg/day IMU-838 in the cumulative number of CUA MRI lesions at Week 24. Additional secondary endpoints involve relapse-related clinical endpoints such as mean annualized relapse rate, proportion of relapse-free patients, and time to relapse. Changes in disease activity will also be measured by the Expanded Disability Status Scale (EDSS) at specified intervals.
Assessments will be conducted using magnetic resonance imaging (MRI) to evaluate disease activity, with MRI-based assessments correlated with quartiles of IMU-838 trough levels at Weeks 6 and 24. The trial will also monitor changes in serum neurofilament levels and other biomarkers at Week 24. Patient-reported outcomes will be collected using the Treatment Satisfaction Questionnaire for Medication at Week 6, Week 24, and the end of the study.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Main treatment period 1. Male or female patient (age ≥18 to 55 years, inclusive)
- Main treatment period 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.
- Main treatment period 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)
- Main treatment period 4. Expanded Disability Status Scale (EDSS) score between 0 and 4.0 (inclusive) at Screening Visit 1
- Main treatment period 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
- Main treatment period 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
- Main treatment period 7. Willingness and ability to comply with the protocol
- Main treatment period 8. Written informed consent given prior to any trial-related procedure
- Inclusion criteria for optional extended treatment period 1. Compleated 24 weeks of main treatment 2. Baseline MRI, a Week 24 MRI, as well as 2 additional post-dose MRIs Continuation criteria for optional extended treatment period 1. In case the initial Week 24 MRI was not evaluated at least partially assessable, availability of a repeated Week 24 MRI 2. Week 24 MRI (initial or repeated one, if applicable) evaluated at least partially assessable
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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Recruiting | 01 Feb 2019 | 57 |
 Germany | Recruiting | 01 Feb 2019 | 20 |
 Poland | Recruiting | 01 Feb 2019 | 60 |
 Romania | Recruiting | 01 Feb 2019 | 5 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
IMU-838 22.5 mg tablet | Test | TABLET | ORAL USE | 45 | 120 | PRD10879434 |
IMU-838 15 mg tablets | Test | TABLET | ORAL USE | 45 | 120 | PRD9427315 |
IMU-838 30 mg tablet | Test | TABLET | ORAL USE | 45 | 120 | PRD10879486 |
Placebo for IMU-838 Tablets | Placebo | N/A | — | — | — | N/A |