Clinical trial • Phase III • Neurology

Vidofludimus calcium for Relapsing multiple sclerosis

Phase III trial of Vidofludimus calcium for Relapsing multiple sclerosis.

Overview

Trial Therapeutic Area
Neurology
Trial Disease
Relapsing multiple sclerosis
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
03-09-2024
First CTIS Authorization Date
15-10-2024

Trial design

Randomised, placebo for imu-838 tablets (matching placebo with identical appearance/labeling); dosing schedule matched to imu-838: 15 mg tablet once daily days 1–7 then 30 mg tablet once daily starting day 8 (placebo administered on same schedule to maintain blinding).-controlled Phase III trial in Germany, Lithuania, Bulgaria and others.

Randomised
Yes
Comparator
Placebo for IMU-838 Tablets (matching placebo with identical appearance/labeling); dosing schedule matched to IMU-838: 15 mg tablet once daily Days 1–7 then 30 mg tablet once daily starting Day 8 (placebo administered on same schedule to maintain blinding).
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
736
Trial Duration For Participant
504

Stratification factors

  • EDSS (≤2.5 vs >2.5)
  • Age (<40 vs ≥40 years)

Eligibility

Recruits 736 Vulnerable population flag selected (isVulnerablePopulationSelected = true). Participants must be able to read and understand provided information and provide written informed consent prior to any trial-related procedure; no description of assent or consent by proxy for minors is provided..

Pregnancy Exclusion
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).
Vulnerable Population
Vulnerable population flag selected (isVulnerablePopulationSelected = true). Participants must be able to read and understand provided information and provide written informed consent prior to any trial-related procedure; no description of assent or consent by proxy for minors is provided.

Inclusion criteria

  • {"criterion_text":"- 1. 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.\n- 4. 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.\n- 5. EDSS score between 0 and 5.5 (inclusive) at SV1.\n- 6. 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.\n- 7. 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.\n- 8. 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.\n- 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

  • {"criterion_text":"- 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).\n- 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."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- 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)","definition_or_measurement_approach":"Time to first confirmed relapse determined by the Independent Neurology Evaluation Committee (INEC); relapse must occur after start of treatment administration and before end of main period (EOMP)."}

Secondary endpoints

  • {"endpoint_text":"- Key secondary efficacy: 1) Total number of new and/or enlarging T2-MRI lesions from baseline (BL, SV2) until Week 48","definition_or_measurement_approach":"Total number of new and/or enlarging T2 MRI lesions measured from baseline (SV2) until Week 48."}

Recruitment

Planned Sample Size
736
Recruitment Window Months
70
Consent Approach
Written informed consent provided by the participant prior to any trial-related procedure; participants must be able to read and understand the trial information. Multiple language ICF/SIS documents are available (documents listed for English, Bulgarian, Lithuanian, Polish, German, Russian and Ukrainian). Reconsent and withdrawal forms are provided; specific age-based assent not applicable (adult-only population).

Geography

Total Number Of Sites
26
Total Number Of Participants
314

Germany

Earliest CTIS Part Ii Submission Date
16-09-2024
Latest Decision Or Authorization Date
21-04-2026
Processing Time Days
582
Number Of Sites
1
Number Of Participants
50

Sites

Site Name
Universitaet Muenster
Department Name
Klinik für Neurologie mit Institut für Translational Neurologie
Contact Person Name
Luisa Klotz
Contact Person Email
luisa.klotz@ukmuenster.de

Lithuania

Earliest CTIS Part Ii Submission Date
16-09-2024
Latest Decision Or Authorization Date
21-04-2026
Processing Time Days
582
Number Of Sites
1
Number Of Participants
20

Sites

Site Name
Lietuvos sveikatos mokslu universiteto ligonine Kauno klinikos
Department Name
Neurology department
Contact Person Name
Renata Balnyte
Contact Person Email
renatabalnyte@gmail.com

Bulgaria

Earliest CTIS Part Ii Submission Date
16-09-2024
Latest Decision Or Authorization Date
22-04-2026
Processing Time Days
583
Number Of Sites
23
Number Of Participants
224

Sites

Site Name
Medical Center Exacta Medica OOD
Department Name
Office of Nervous Diseases
Contact Person Name
Albena Antimova
Contact Person Email
a.antimova@mail.bg
Site Name
University Multiprofile Hospital For Active Treatment St. Ivan Rilski EAD
Department Name
Neurology Clinic
Contact Person Name
Penko Shotekov
Contact Person Email
shotekov@abv.bg
Site Name
Multiprofile Hospital For Active Treatment Avis Medika OOD
Department Name
Department of Nervous Diseases
Contact Person Name
Hristo Lilovski
Contact Person Email
hristolilovski@gmail.com
Site Name
Multiprofile Hospital For Active Treatment In Neurology And Psychiatry St. Naum EAD
Department Name
Clinic of nervous diseases for movement disorders, Department for Multiple Sclerosis
Contact Person Name
Ivan Milanov
Contact Person Email
prof.ivan.milanov@gmail.com
Site Name
Mnogoprofilna Bolnitsa Za Aktivno Lechenie Puls AD
Department Name
Department of Nervous Diseases
Contact Person Name
Sasho Kastrev
Contact Person Email
kastrev@hotmail.com
Site Name
Multi-profile Hospital for Active Treatment Heart and Brain EAD
Department Name
Second department of neurological diseases
Contact Person Name
Ivan Dimitrov
Contact Person Email
indimitrov@yahoo.com
Site Name
Multi-profile Hospital for Active Treatment Heart and Brain EAD
Department Name
Clinic of Neurology Diseases
Contact Person Name
Plamen Bozhinov
Contact Person Email
psbozhinov@yahoo.com
Site Name
Alexandrovska University Hospital
Department Name
Neurology Clinic
Contact Person Name
Ivaylo Tarnev
Contact Person Email
itournev@emhpf.org
Site Name
MBAL Sveta Marina EAD
Department Name
First Clinic of Neurology Diseases
Contact Person Name
Ara Kaprelyan
Contact Person Email
arakapri07@yahoo.co.uk
Site Name
Medical Center Vita 1 Ltd.
Department Name
Neurology Office
Contact Person Name
Plamen Petkov
Contact Person Email
pn.petkov@abv.bg
Site Name
Multiprofile Hospital For Active Treatment In Neurology And Psychiatry St. Naum EAD
Department Name
Clinic for Intensive treatment of neurological diseases
Contact Person Name
Paraskeva Stamenova
Contact Person Email
par.stamenova@gmail.com
Site Name
Multispecialty hospital for active treatment Sveta Sofia EOOD
Department Name
Department of neurological diseases
Contact Person Name
Emil Olevski
Contact Person Email
emil_olevski@abv.bg
Site Name
Uniteversity Muliprofile Hospital For Active Treatment Tsaritsa Yoanna-Isul EAD
Department Name
Clinic for intensive treatment of nervous diseases
Contact Person Name
Evgenia Vasileva-Ruscheva
Site Name
Diagnostic And Consultative Center Neoclinic EAD
Department Name
Office of Nervous Diseases
Contact Person Name
Rosen Ikonomov
Contact Person Email
drros@abv.bg
Site Name
Military Medical Academy
Department Name
Clinic of Neurology Diseases
Contact Person Name
Stratieva Stratina
Contact Person Email
stratina@abv.bg
Site Name
University Multiprofile Hospital For Active Treatment Dr. Georgi Stranski EAD
Department Name
Neurology Clinic
Contact Person Name
Maya Danovska
Contact Person Email
mdanovska@yahoo.com
Site Name
Military Medical Academy
Department Name
Clinic of Nervous Disease
Contact Person Name
Hristina Dimitrova
Contact Person Email
drhrisi@abv.bg
Site Name
Alexandrovska University Hospital
Department Name
Neurology Clinic
Contact Person Name
Latchezar Traykov
Contact Person Email
traykov_l@yahoo.fr
Site Name
Universitetska Mnogoprofilna Bolnitsa Za Aktivno Lechenie Medika Ruse OOD
Department Name
Department of Neurology Diseases
Contact Person Name
Rositsa Krasteva
Contact Person Email
rosikrasteva@abv.bg
Site Name
University Multiprofile Hospital For Active Treatment Kaspela EOOD
Department Name
Department of Neurology Diseases
Contact Person Name
Anastasiya Trenova
Contact Person Email
atrenova@yahoo.com
Site Name
University Multiprofile Hospital For Active Treatment And Emergency Medicine N I Pirogov
Department Name
Department of Neurology Diseases
Contact Person Name
Maria Dimitrova
Contact Person Email
dr.m.i.dimitrova@gmail.com
Site Name
University Multiprofile Hospital For Active Treatment Saint Georgi EAD
Department Name
Neurology Clinic
Contact Person Name
Georgi Slavov
Contact Person Email
dr.georgi.slavov@gmail.com
Site Name
Medical Institute Ministry Of Interior
Department Name
Clinic of Nervous Diseases
Contact Person Name
Kosta Kostov
Contact Person Email
drkostov@abv.bg

Poland

Earliest CTIS Part Ii Submission Date
16-09-2024
Latest Decision Or Authorization Date
21-04-2026
Processing Time Days
582
Number Of Sites
1
Number Of Participants
20

Sites

Site Name
Niepubliczny Zaklad Opieki Zdrowotnej Neuromed M. I M. Nastaj. sp.p.
Contact Person Name
Marcin Nastaj
Contact Person Email
marcinnastaj@gmail.com

Sponsor

Primary sponsor

Full Name
Immunic AG
Organisation Type
Pharmaceutical company
Country Of Registered Address
Germany

Contract research organisations

Name
FGK Clinical Research GmbH
Responsibilities
code 11
Name
Worldwide Clinical Trials Holdings Inc.
Responsibilities
codes 1,10,11,12,2,6,7,8,9
Name
WCG Clinical - Trifecta
Responsibilities
code 15; Patient and clinical outcome scores

Third parties

  • {"country":"Germany","full_name":"FGK Clinical Research GmbH","duties_or_roles":"code 11","organisation_type":"Pharmaceutical company"}
  • {"country":"Spain","full_name":"Suvoda LLC","duties_or_roles":"code 3","organisation_type":"Industry"}
  • {"country":"Germany","full_name":"SCRATCH Pharmacovigilance GmbH & Co. KG","duties_or_roles":"code 8","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"Cerba Research","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"France","full_name":"Keosys","duties_or_roles":"code 15; Technical MRI qualification of participating sites, set up of portal for upload of MRI images","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Germany","full_name":"MENAL Gesellschaft fuer medizinische und naturwissenschaftliche Laboranalytik mbH","duties_or_roles":"code 15; PK data analysis and modelling","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Worldwide Clinical Trials Holdings Inc.","duties_or_roles":"codes 1,10,11,12,2,6,7,8,9","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"WCG Clinical - Trifecta","duties_or_roles":"code 15; Patient and clinical outcome scores","organisation_type":"SME"}
  • {"country":"Bulgaria","full_name":"Resbiomed OOD","duties_or_roles":"codes 1,12","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Germany","full_name":"MVZ Medizinisches Labor Nord MLN GmbH","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"Italy","full_name":"Siena Imaging S.r.l.","duties_or_roles":"codes 15 (MRI post processing, central MRI reading/data analysis) and 4","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Medidata Solutions International Limited","duties_or_roles":"code 7","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Autocruitment LLC","duties_or_roles":"code 15; Screening patients services for Bulgaria, Lithuania, Poland, and Romania","organisation_type":"Industry"}
  • {"country":"Bulgaria","full_name":"Resbiomed OOD (additional listing in thirdParties)","duties_or_roles":"codes 1,12","organisation_type":"Hospital/Clinic/Other health care facility"}

Investigational products

Investigational Product Name
IMU-838 15 mg tablets
Active Substance
Vidofludimus calcium
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Authorised
Starting Dose
15 mg once daily (Days 1–7)
Dose Levels
15 mg; 30 mg
Frequency
Once daily
Maximum Dose
30 mg
Dose Escalation Increase
Initial 15 mg once daily (Days 1–7) then increase to 30 mg once daily (from Day 8)
Investigational Product Name
IMU-838 30 mg tablet
Active Substance
Vidofludimus calcium
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Authorised
Starting Dose
30 mg once daily (from Day 8)
Dose Levels
15 mg; 30 mg
Frequency
Once daily
Maximum Dose
30 mg
Dose Escalation Increase
Initial 15 mg once daily (Days 1–7) then 30 mg once daily
Investigational Product Name
Placebo for IMU-838 Tablets
Modality
Other
Routes Of Administration
Oral (matching placebo)
Route
Oral
Starting Dose
Placebo matching 15 mg once daily (Days 1–7)
Dose Levels
Placebo matched to 15 mg then 30 mg schedule
Frequency
Once daily
Dose Escalation Increase
Placebo given on same schedule: initial placebo '15 mg' equivalent Days 1–7 then '30 mg' equivalent from Day 8

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