Phase 3 Randomized, Double‑Blind Study of IMU‑838 (vidofludimus calcium) versus Placebo in Adults with Relapsing Multiple Sclerosis
- Trial ID
- 2024-514618-11-00
- Protocol
- P3-IMU-838-RMS-01
- Sponsor
- Immunic AG
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of IMU-838 compared to placebo in adult patients with active **Relapsing Multiple Sclerosis** (RMS). The focus is on delaying the occurrences of relapses, specifically measuring the time to first relapse (T2FR). This is clinically relevant as it aims to provide a therapeutic option that could potentially reduce the frequency of relapses in RMS, thereby improving patient outcomes and quality of life.
Participants
The clinical trial involves a total of **627 participants** diagnosed with **Relapsing Multiple Sclerosis** (RMS). The study population includes both male and female adults aged between 18 and 55 years. Participants were selected based on their established diagnosis of multiple sclerosis according to the 2017 McDonald Criteria, with specific subtypes of relapsing-remitting MS and active secondary progressive MS as defined by the Lublin criteria. The trial population comprises individuals whose disease-modifying treatments have failed due to efficacy, safety, or tolerability issues, or those with contraindications or lack of access to treatment. Participants are required to have an **Expanded Disability Status Scale (EDSS)** score between 0 and 5.5. Lifestyle considerations such as diet and physical activity are not specified, but participants must comply with protocol requirements, including contraceptive measures for those of childbearing potential. The trial does not specify any particular lifestyle habits or restrictions beyond the medical criteria outlined.
Plans and Procedures
The clinical trial is a **randomized**, **double-blind**, controlled study designed to evaluate the efficacy, safety, and tolerability of IMU-838 compared to placebo in adults with **relapsing multiple sclerosis**. The trial is structured as a Phase 3 study and aims to demonstrate the efficacy of IMU-838 in delaying the occurrence of relapses, with the primary endpoint being the time to first confirmed relapse. The trial is expected to run until April 2032, with recruitment having commenced in February 2023.
Participants will be involved in the study for a maximum of 72 weeks, during which they will undergo a series of study visits. The sequence of visits includes an initial screening visit to confirm eligibility based on criteria such as age, diagnosis according to the 2017 McDonald Criteria, and evidence of active disease. Following the screening, participants will be randomized to receive either IMU-838 or placebo, administered orally in tablet form. The study includes regular follow-up visits to monitor safety and efficacy, with assessments such as MRI scans and evaluations of disability status using the Expanded Disability Status Scale (EDSS).
The end-of-study visit, scheduled at Week 72, will serve as the final assessment point, including a comprehensive evaluation of the primary and secondary endpoints. Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with the study protocol, or if the investigator deems it necessary for their safety. The trial's design ensures that all participants, regardless of their assigned treatment group, receive consistent monitoring and care throughout the study duration.
Treatment
The clinical trial involves the administration of **IMU-838**, a chemically synthesized medication, in two different dosages. The first experimental medication is **IMU-838 15 mg tablets**, containing the active substance **vidofludimus calcium**. This pharmaceutical form is a tablet, intended for **oral use**. The maximum daily dose for this formulation is 15 mg, with a total maximum dose of 50 mg over a treatment period of 1 day. The administration schedule is designed to ensure participant compliance, with dosing monitored throughout the trial.
The second experimental medication is **IMU-838 30 mg tablet**, also containing **vidofludimus calcium**. This formulation is similarly a tablet for **oral use**. The maximum daily dose for this formulation is 30 mg, with a total maximum dose of 50 mg over a treatment period of 100 days. The administration of this dosage is structured to maintain adherence to the dosing schedule, with compliance monitoring implemented as part of the trial protocol.
In addition to the experimental medications, a **placebo** is utilized in the study. The placebo is designed to match the **IMU-838 tablets** in appearance but does not contain the active substance **vidofludimus calcium**. The placebo serves as a comparator treatment to evaluate the efficacy and safety of **IMU-838** in participants with **relapsing multiple sclerosis**. The administration of the placebo follows the same oral route and dosing schedule as the active treatments, ensuring blinding and consistency across the study arms.
Efficacy
Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the **time to first confirmed relapse**, as determined by the Independent Neurology Evaluation Committee (INEC). This relapse must occur after the start of treatment administration and before the end of the main period, with data censored at a maximum of 72 weeks, corresponding to Visit 8 or the end of the main period (EOMP).
Secondary efficacy endpoints include several key measures: changes in the total volume of new T2-lesions from baseline magnetic resonance imaging (MRI) until Week 24; time to 12-week confirmed disability worsening (12wCDW) as assessed on the Expanded Disability Status Scale (EDSS), with data censored until Week 72 or EOMP; time to confirmed clinically relevant changes in the Symbol Digit Modalities Test (SDMT) during the main period, also censored at Week 72 or EOMP; and the annualized rate of percentage changes in whole brain volume from baseline MRI to the MRI at Visit 8 or EOMP. These endpoints will be measured and analyzed according to the protocol, ensuring a comprehensive evaluation of the treatment's efficacy in patients with relapsing multiple sclerosis.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male or female patient (age ≥18 to ≤55 years) 2. Patients with an established diagnosis of MS according to 2017 McDonald Criteria [41] 3. Patients with RMS comprising of relapsing remitting MS (RRMS) and active secondary progressive MS, both defined according to Lublin criteria 1996 and 2014. 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.
- Active disease as defined by Lublin 2014 evidenced prior to Screening by: a. At least 2 relapses(a) in the last 24 months before randomization, or b. At least 1 relapse(a) 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. (a) Relapses and/or Gd+ MRI lesions must have been assessed and documented by a physician in the patient files.
- EDSS score between 0 and 5.5 (inclusive) at SV1.
- Female patients: a. must be of non-childbearing potential, i.e., 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 trial 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 (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). vi.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 not acceptable methods of contraception). d.Barrier methods of contraception include: i.condom.
- Male patients must agree not to father a child or to donate sperm starting at SV1, throughout the clinical trial, 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 use condoms while taking the IMP to avoid exposure of the fetus to the IMP.
- Willingness and ability to comply with the protocol. 9. Patients are able to read and understand the given information about the trial (including their language capabilities) and provide written informed consent prior to any trial-related procedure.
- Inclusion criteria for the EP: 1.Completed full visit schedule of the MP up to 72 weeks of (with the V8/EOMP completed and no more than 1 regular study visit omitted), independent of the patient's treatment: a.Double-blind treatment, or b.active treatment option (ATO) within MP, or c.Rescue treatment outside this trial (observational phase) but with double-blind treatment of at least 24 weeks in this trial and approved by the sponsor. 2. Performed a full and complete Week 72 visit (Visit 8; which also serves as an EOMP visit and includes the Visit 8 MRI examination).
Exclusion Criteria
- Exclusion Criteria for the Main Period of the Trial: 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 of 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. Please refer to protocol for further exclusion criteria (Therapy, immune response, other medical history and concomitant disease as well as general exclusion criteria).
- Exclusion Criteria for the EP: 1. Any ongoing, clinically significant (as assessed by the investigator) TEAE (started after intake of IMP) or laboratory abnormality (including blood chemistry and urinalysis) that, upon discretion of the investigator, should prohibit further treatment with trial medication in this trial(a). 2. Significant treatment non-compliance (defined as having taken <70% of trial medication) or trial non-compliance during the MP (as assessed by the investigator, in consultation with the medical monitor), and/or inability or unwillingness to follow instructions by trial personnel. 3. Multiple significant protocol deviations during the MP that are assessed by the investigator, in consultation with the medical monitor, to negatively affect further patient cooperation in this trial. 4. Use of experimental/investigational drug (with the exception of COVID-19 vaccines) and/or participation in another clinical trial of an investigational drug throughout the duration of the EP. 5. Any treatment mentioned in the Therapy Exclusion Criteria 9, 10, 11, 12, and 13. (a) If a TEAE(s) is the reason for exclusion from the EP open-label treatment period, the eligibility can be re-assessed up to 12 weeks following the last treatment in the MP.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Not Recruiting | 13 Feb 2023 | 224 |
 Germany | Not Recruiting | 13 Feb 2023 | 50 |
 Lithuania | Not Recruiting | 13 Feb 2023 | 20 |
 Poland | Not Recruiting | 13 Feb 2023 | 20 |
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 |
|---|---|---|---|---|---|---|
Placebo for IMU-838 Tablets | Placebo | N/A | — | — | — | N/A |
IMU-838 15 mg tablets | Test | TABLET | ORAL USE | 15 | 1 | PRD9427315 |
IMU-838 30 mg tablet | Test | TABLET | ORAL USE | 30 | 100 | PRD10879486 |