Efficacy, Safety, and Tolerability of Vidofludimus Calcium in Progressive Multiple Sclerosis: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial
- Trial ID
- 2024-514617-35-00
- Protocol
- P2-IMU-838-PMS
- Sponsor
- Immunic AG
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this multicenter, randomized, double-blind, placebo-controlled study is to evaluate the **efficacy** of IMU-838 compared to placebo in patients with progressive forms of Multiple Sclerosis. This will be assessed through quantitative magnetic resonance imaging (MRI) analysis for whole brain atrophy using the Structural Image Evaluation using Normalization of Atrophy (SIENA) method during the Main Treatment period. The clinical relevance of this objective lies in its potential to provide insights into the effectiveness of IMU-838 in slowing or preventing brain atrophy, a critical factor in the progression of Multiple Sclerosis.
Participants
The clinical trial involves a total of **237 participants** diagnosed with **progressive forms of Multiple Sclerosis**. The study population includes both male and female adults aged 18 to 65 years. Participants were selected based on specific criteria, including the absence of relapse in the last 24 months and a diagnosis of either secondary progressive multiple sclerosis (SPMS) or primary progressive multiple sclerosis (PPMS) according to established criteria. The participants exhibit an Expanded Disability Status Scale (EDSS) score ranging from 3.0 to 6.5. The trial population includes individuals with evidence of disability worsening not related to a relapse within the last 24 months. Lifestyle considerations such as diet and physical activity are not specified. The study includes a vulnerable population, and participants are required to comply with specific contraceptive measures to prevent pregnancy during the trial. The selection process ensures that participants are willing and able to adhere to the study protocol, with informed consent obtained prior to any study-related procedures.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy, safety, and tolerability of IMU-838 in patients with **progressive multiple sclerosis**. The trial aims to assess the efficacy of IMU-838 versus placebo by measuring whole brain atrophy using quantitative magnetic resonance imaging (MRI) analysis during the Main Treatment (MT) period. The study involves the administration of IMU-838 in two dosages, 22.5 mg and 45 mg tablets, alongside a placebo, all administered orally. The trial is expected to run until December 31, 2032, with recruitment having started on November 15, 2021.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on specific criteria, such as age, disease status, and disability progression. Following successful screening, participants will be randomized to receive either the active treatment or placebo. The study includes multiple follow-up visits to monitor safety, efficacy, and adherence to the protocol. These visits will involve assessments such as MRI scans, clinical evaluations, and laboratory tests. The end-of-study visit will conclude the participant's involvement, where final assessments will be conducted to evaluate the primary and secondary endpoints.
The expected length of participant involvement is up to 120 weeks, with conditions for early termination including non-compliance with the protocol, adverse events, or withdrawal of consent. The primary endpoint is the annualized rate of percent brain volume change during the MT period, while secondary endpoints include the time to 24-week confirmed disability worsening. The trial is conducted under strict ethical guidelines, ensuring the safety and well-being of participants 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 the **IMU-838 22.5 mg tablet**, which contains the active substance **vidofludimus calcium**. This pharmaceutical form is a tablet intended for **oral use**. The maximum daily dose for this formulation is 45 mg, with a total maximum dose of 50 mg over a treatment period of up to 7 days. The administration schedule is designed to ensure participant compliance, with dosing monitored throughout the trial.
The second experimental medication is the **IMU-838 45 mg tablet**, also containing **vidofludimus calcium**. This formulation is similarly a tablet for **oral use**. The maximum daily dose is 45 mg, with a total maximum dose of 50 mg, but the treatment period extends up to 120 days. As with the 22.5 mg tablet, dosing schedules are carefully monitored to ensure adherence and to evaluate the efficacy and safety of the treatment in patients with progressive multiple sclerosis.
In addition to the experimental medications, a **placebo** is used as a comparator in this double-blind, placebo-controlled study. The placebo is designed to match the **IMU-838 tablets** in appearance but does not contain the active substance **vidofludimus calcium**. The use of a placebo allows for the assessment of the true efficacy and safety of the experimental treatments by providing a baseline for comparison. The placebo administration follows the same oral route and dosing schedule as the active treatments to maintain the study's blinding integrity.
Efficacy
The efficacy of IMU-838 in patients with Progressive Multiple Sclerosis (PMS) will be assessed through a multicenter, randomized, double-blind, placebo-controlled study. The primary endpoint for evaluating efficacy is the annualized rate of percent brain volume change (PBVC) during the Main Treatment (MT) period. This will be measured using quantitative magnetic resonance imaging (MRI) analysis, specifically employing the Structural Image Evaluation using Normalization of Atrophy (SIENA) method. Secondary endpoints include the time to 24-week confirmed disability worsening, assessed on a composite of the Expanded Disability Status Scale (EDSS), 9-Hole Peg Test (9-HPT), or Timed 25-foot Walk (T25-FW) during the MT period.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Adult patients, age 18 to 65 years (inclusive). 2. No evidence of relapse in the last 24 months before randomization, AND Patients diagnosed with either a) SPMS, in patients showing evidence of Gd+ MRI lesions (active SPMS) in the brain or spinal cord, or without Gd+ MRI lesions (non-active SPMS) in the last 12 months, OR b) PPMS according to 2017 revised McDonald Criteria and the 2013 revised classification of disease courses with a disease duration of the progressive disease of ≤10 years
- EDSS score at screening between 3.0 to 6.5 (both inclusive)
- Evidence of disability worsening not temporarily related to a relapse in the last 24 months before randomization, adjudicated by a central independent reviewer, and documented as: a) An increase of EDSS of at least 1.0 point with Screening EDSS of up to 5.5 (inclusive) and 0.5 point for Screening EDSS 6.0 or 6.5 (as documented in patient files in the last 24 months before randomization), OR b) A 20% worsening (or more) in 25-foot walk time or 9-hole peg test time in either hand (as documented in patient files in the last 24 months before randomization), OR c) A written summary of the clinical evidence of disability worsening in the previous 24 months before randomization through a retrospective assessment of disease worsening from patient files.
- 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 at Day 1 (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 of 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 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 [e.g., 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.
- 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 Note: Simultaneous use of male and female condoms with or without any other contraception methods is not permitted. c) If they have a female partner of childbearing potential, the partner should use a highly effective contraceptive method as outlined in inclusion criterion 4. 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.
- Written informed consent given by the patient before the beginning of any study-related procedure. For more information, please refer to Clinical Study Protocol.
- Inclusion Criteria for the OLE Period 1. Completed 120 weeks of MT period or have confirmed 24-week disability worsening or the patient was in the MT period when the study reached the MT termination event, at which time, the patient could enter the OLE period.
Exclusion Criteria
- MS-related exclusion criteria: 1. Any disease other than MS that may better explain the signs and symptoms, including a history of complete transverse myelitis. 2. Clinical signs or presence of laboratory findings suggestive for neuromyelitis optica spectrum disorders (NMOSD) or myelin oligodendrocyte glycoprotein (MOG)-associated encephalomyelitis (i.e., presence of aquaporin-4 antibodies or anti-MOG antibodies). 3. Any MRI finding, atypical for MS, including but not limited to a longitudinally extensive spinal cord lesion. 4. Any active and uncontrolled coexisting autoimmune disease, other than MS (except for type 1 diabetes mellitus and inflammatory bowel disease).
- Therapy-related exclusion criteria: 5. Any previous or current use of the following MS treatments: a) alemtuzumab or belimumab, including their biosimilars, b) cladribine, c) total lymphoid irradiation, and d) bone marrow or stem cell transplantation. 6. Any use of the following MS treatments before the date of randomization (see table in study protocol) 7. Any use of adrenocorticotrophic hormone (ACTH) or occasional use of systemic corticosteroids (oral or intravenous) 30 days before SV2. 8. Use of any investigational product within 8 weeks or 5× the respective PK half-life before the date of informed consent, whichever is longer, and throughout the study. For some investigational products, prolonged biological effects beyond 8 weeks should be considered. For more information, please refer to Clinical Study Protocol.
- Exclusion Criteria for the OLE Period: Patients meeting any of the following criteria will be ineligible to participate in the OLE Period of the study: 1. Any ongoing, clinically significant (as assessed by the Investigator) treatment-emergent AE or laboratory abnormality (including blood biochemistry and urinalysis) that can jeopardize the patient's safety, in agreement with the medical monitor. 2. Significant study or treatment non-compliance (<80% or >125%) during the MT period, and/or inability or unwillingness to follow instructions by study personnel. 3. The lack of interpretable BL or EoMT MRI or the omission of more than one other MRI during the MT. 4. Use of experimental/investigational drug (except for COVID-19 vaccines approved by emergency use authorization or similar expanded access schemes) and/or participation in another clinical study of an investigational drug throughout the duration of the OLE treatment period.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Recruiting | 15 Nov 2021 | 95 |
 Czechia | Recruiting | 15 Nov 2021 | 9 |
 Germany | Recruiting | 15 Nov 2021 | 13 |
 The Netherlands | Recruiting | 15 Nov 2021 | — |
 Poland | Recruiting | 15 Nov 2021 | 102 |
 Romania | Recruiting | 15 Nov 2021 | 3 |
| Netherlands | — | — | 8 |
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 | 7 | PRD10879434 |
Placebo for IMU-838 Tablets | Placebo | N/A | — | — | — | N/A |
IMU-838 45 mg tablet | Test | TABLET | ORAL USE | 45 | 120 | PRD10879487 |