VIDOFLUDIMUS CALCIUM for Relapsing-remitting multiple sclerosis

Inclusion criteria

• {"criterion_text":"- Main treatment period 1. Male or female patient (age ≥18 to 55 years, inclusive)\n- 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.\n- 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)\n- Main treatment period 4. Expanded Disability Status Scale (EDSS) score between 0 and 4.0 (inclusive) at Screening Visit 1\n- 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\n- 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\n- Main treatment period 7. Willingness and ability to comply with the protocol\n- Main treatment period 8. Written informed consent given prior to any trial-related procedure\n- 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

• {"criterion_text":"- 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)\n- 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\n- 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"}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Measured by MRI: cumulative number of combined unique active (CUA) MRI lesions up to Week 24 for C1 (45 mg/day vs placebo). For C2, between-treatment differences in cumulative number of CUA MRI lesions and gadolinium-enhancing (Gd+) MRI lesions up to Week 24."}

Secondary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Cumulative number of CUA MRI lesions up to Week 24 measured by MRI; hierarchical testing relative to primary efficacy"}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Between-treatment comparison of cumulative CUA MRI lesions at Week 24 as measured by MRI"}
• {"endpoint_text":"- Efficacy: 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","definition_or_measurement_approach":"Between-treatment comparisons of cumulative CUA MRI lesions (MRI-based measures) at specified timepoints"}
• {"endpoint_text":"- 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: Mean annualized relapse rate (during main and extended treatment period); Proportion of relapse-free patients up to Week 24 and at extended periods thereafter; Time to relapse at time of final analysis of main part","definition_or_measurement_approach":"Clinical relapse assessments documented by physician; calculation of annualized relapse rate, proportion relapse-free up to Week 24, and time-to-relapse analyses"}
• {"endpoint_text":"- C2: Number of relapses in each treatment arm","definition_or_measurement_approach":"Count of physician-documented relapses per arm"}
• {"endpoint_text":"- C1: Differences between treatments in changes of disease activity as measured by the following clinical parameters: Mean change in the EDSS as compared to Baseline during the main and extended period (every 12 weeks starting at Week 12); Proportion of patients with EDSS progression during the main and extended period (every 12 weeks starting at Week 12, and cumulatively)","definition_or_measurement_approach":"EDSS scores assessed at baseline and every 12 weeks (then every 24 weeks in OLE after protocol amendment); mean change and proportion with progression calculated"}
• {"endpoint_text":"- C2: Change of EDSS from Baseline to Weeks 12 and 24 C1: Correlation of MRI-based assessments with quartiles of IMU-838 trough levels at Week 6 and Week 24 C2: Correlation of MRI-based assessments with quartiles of IMU-838 trough levels at Week 24","definition_or_measurement_approach":"EDSS change from baseline at Weeks 12 and 24; correlations between MRI outcomes and plasma trough concentrations (PK) at specified weeks"}
• {"endpoint_text":"- Safety C1+C2: AEs, serious AEs and clinically significant laboratory abnormalities (as assessed by the investigator)","definition_or_measurement_approach":"Adverse events collected and categorized; laboratory abnormalities per protocol-defined criteria and investigator assessment"}
• {"endpoint_text":"- C1+C2: AEs of special interest: Red blood cell urine positive, at least of moderate intensity; Hematuria; Retroperitoneal colicky pain with suspected or confirmed nephrolithiasis","definition_or_measurement_approach":"Events of special interest monitored and recorded per protocol definitions (urinalysis, clinical assessments)"}
• {"endpoint_text":"- C1: Proportion of patients treated with 30 mg/day or 45 mg/day IMU 838 as compared to placebo who experienced at least one of the following AEs","definition_or_measurement_approach":"Proportion of patients experiencing specified AEs compared between arms"}
• {"endpoint_text":"- C2: Proportion of patients treated with 10 mg/day as compared to placebo who experienced at least one of the following AEs:Neutropenia; Lymphopenia; Diarrhea; Alopecia; Hemorrhage; Abnormalities in alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, and total bilirubin with both elevations ˃1.5 x ULN and ≥35% elevated compared to Baseline","definition_or_measurement_approach":"Proportion with listed laboratory/clinical AEs compared between arms; labs measured and compared to ULN and baseline"}
• {"endpoint_text":"- ECG, physical examination, and vital signs","definition_or_measurement_approach":"Standard safety assessments: ECGs, physical exams, vitals at scheduled visits"}
• {"endpoint_text":"- C1: Micro ribonucleic acid-122 expression (Change from Baseline to 4 hours after first dose)","definition_or_measurement_approach":"miRNA-122 expression measured in samples pre-dose and 4 hours post first dose; change from baseline assessed"}
• {"endpoint_text":"- C1: Presence of John Cunningham virus (JCV) deoxyribonucleic acid (DNA) in urine in patients with detectable JCV-DNA in urine at Screening Visit 1, at Week 24, and at EoS","definition_or_measurement_approach":"JCV DNA presence in urine measured by molecular assay at screening, Week 24 and end of study"}
• {"endpoint_text":"- C1+C2: Time to treatment discontinuation for any reason","definition_or_measurement_approach":"Time from randomization to treatment discontinuation recorded and analyzed"}
• {"endpoint_text":"- C1+C2: Rate of treatment discontinuations up to Week 24","definition_or_measurement_approach":"Proportion/rate of discontinuations up to Week 24"}
• {"endpoint_text":"- Pharmacokinetics C1+C2: Population PK at Week 6 (3-10 hours post-dose) C1+C2: Plasma trough levels of IMU-838 at Days 7 and Weeks 6, 12, 18, and 24","definition_or_measurement_approach":"Population PK sampling at Week 6 (3–10 hours post-dose) and trough plasma levels at specified timepoints"}
• {"endpoint_text":"- Pharmacodynamics C1: Changes from Baseline in lymphocyte subset parameters as measured by flow cytometry at Weeks 6 and 24 (in selected Biomarker Centers only)","definition_or_measurement_approach":"Flow cytometry assessments of lymphocyte subsets at baseline and Weeks 6 and 24 (selected centers)"}
• {"endpoint_text":"- C1: Changes from Baseline in biased T-cell clonal repertoire based on T-cell receptor deep sequencing at Weeks 6 and 24 (in selected Biomarker Centers only)","definition_or_measurement_approach":"T-cell receptor deep sequencing at baseline and Weeks 6 and 24 in selected biomarker centers; analysis of clonal repertoire changes"}
• {"endpoint_text":"- C1+C2: Changes from Baseline in serum neurofilament at Week 24 C2: Changes in serum C4 (7α-hydroxy-4-cholesten-3-one) C2: Changes in serum fibroblast growth factor 19 (FGF-19)","definition_or_measurement_approach":"Serum biomarker assays for neurofilament, C4, and FGF-19 at baseline and Week 24"}
• {"endpoint_text":"- Health outcome (C1) Treatment Satisfaction Questionnaire for Medication at Week 6, Week 24 and EoS","definition_or_measurement_approach":"Patient-reported Treatment Satisfaction Questionnaire for Medication administered at specified visits"}

Methods

• K1_Recruitment arrangements_Declaration documents present (declarations of recruitment arrangements) for multiple countries (document titles present in documents list).
• Digital advertising materials for Poland: 'K2_Recruitment material_advertising website_pl', 'K2_Recruitment material_website banner_pl', 'K2_Recruitment material_advertising leaflet_pl' (website/banner/leaflet channels indicated in documents list).

Bulgaria

Earliest CTIS Part Ii Submission Date

19-08-2024

Latest Decision Or Authorization Date

13-03-2026

Processing Time Days

571

Number Of Sites

14

Number Of Participants

57

Germany

Earliest CTIS Part Ii Submission Date

04-09-2024

Latest Decision Or Authorization Date

17-03-2026

Processing Time Days

559

Number Of Sites

1

Number Of Participants

20

Romania

Earliest CTIS Part Ii Submission Date

19-08-2024

Latest Decision Or Authorization Date

23-03-2026

Processing Time Days

581

Number Of Sites

2

Number Of Participants

5

Poland

Earliest CTIS Part Ii Submission Date

19-08-2024

Latest Decision Or Authorization Date

16-03-2026

Processing Time Days

574

Number Of Sites

5

Number Of Participants

60

Primary sponsor

Full Name

Immunic AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Contract research organisations

Name

FGK Clinical Research GmbH

Responsibilities

sponsorDuties codes: ["5"]

Name

WCT Worldwide Clinical Trials GER GmbH

Responsibilities

sponsorDuties codes: ["8"]

Name

Clinical Trial Center S.R.L.

Responsibilities

sponsorDuties codes: ["1","12"]

Third parties

• {"country":"Belgium","full_name":"PharmaLex Belgium","duties_or_roles":"sponsorDuties codes: [\"10\"]","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"MVZ Medizinisches Labor Nord MLN GmbH","duties_or_roles":"sponsorDuties codes: [\"4\"]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Quanterix Corp.","duties_or_roles":"sponsorDuties codes: [\"4\"]","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"WCT Worldwide Clinical Trials GER GmbH","duties_or_roles":"sponsorDuties codes: [\"8\"]","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"SCRATCH Pharmacovigilance GmbH & Co. KG","duties_or_roles":"sponsorDuties codes: [\"8\"]","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Siena Imaging S.r.l.","duties_or_roles":"sponsorDuties codes: [\"4\"]","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"FGK Clinical Research GmbH","duties_or_roles":"sponsorDuties codes: [\"5\"]","organisation_type":"Pharmaceutical company"}
• {"country":"Romania","full_name":"Clinical Trial Center S.R.L.","duties_or_roles":"sponsorDuties codes: [\"1\",\"12\"]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"MENAL Gesellschaft fuer medizinische und naturwissenschaftliche Laboranalytik mbH","duties_or_roles":"sponsorDuties codes: [\"4\"]","organisation_type":"Pharmaceutical company"}
• {"country":"Ukraine","full_name":"Dila LLC","duties_or_roles":"sponsorDuties codes: [\"4\"]","organisation_type":"Industry"}
• {"country":"Germany","full_name":"Universitaetsklinikum Muenster AöR","duties_or_roles":"sponsorDuties codes: [\"4\"]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"France","full_name":"Keosys","duties_or_roles":"sponsorDuties codes: [\"7\"]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Germany","full_name":"Verum.De GmbH","duties_or_roles":"sponsorDuties codes: [\"1\"]","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"IMGM Laboratories GmbH","duties_or_roles":"sponsorDuties codes: [\"4\"]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Anju Software Inc.","duties_or_roles":"sponsorDuties codes: [\"3\",\"7\"]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Bulgaria","full_name":"Resbiomed OOD","duties_or_roles":"sponsorDuties codes: [\"1\"]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Switzerland","full_name":"Neurostatus-UHB AG","duties_or_roles":"sponsorDuties codes: [\"15\"] value: \"Secondary Pads, EDSS scoring pads\"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Nuvisan GmbH","duties_or_roles":"sponsorDuties codes: [\"4\"]","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"GBA Central Lab Services GmbH","duties_or_roles":"sponsorDuties codes: [\"4\"]","organisation_type":"Laboratory/Research/Testing facility"}