Randomized, double-blind, placebo-controlled, multicenter Phase 2 trial assessing the effect of IMU-838 on disease activity, as measured by magnetic resonance imaging (MRI), as well as safety and tolerability in patients with relapsingremitting multiple sclerosis (RRMS) (EMPhASIS)

Start 23 Jan 2019 · Status Authorised, recruiting · 4 EU/EEA countries · 22 sites · Protocol P2-IMU-838-MS

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)

Status Authorised, recruiting

Participants planned 270

Countries 4

Sites 22

Relapsing-remitting multiple sclerosis

Cohort 1 (i.e. the main study): Primary • To evaluate the efficacy of 45 mg/day IMU-838 in the treatment of RRMS based on MRI assessments Cohort 2 (i.e. the sub-study): Primary • To obtain more efficacy and safety data of IMU-838 in patients with RRMS and to allow pharmacodynamic modelling of the dose response.

Key facts

Sponsor: Immunic AG
Participant type: Patients
Age range: 18-64 years
Gender: Male and Female
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
Trial duration: 23 Jan 2019 → ongoing
Decision date (initial): 2024-09-11
Transition trial: Yes
Low-intervention: No
Rare-disease indication: No
Vulnerable population: Yes

External identifiers

EU CT number: 2024-516739-29-00
EudraCT number: 2018-001896-19
ClinicalTrials.gov: NCT03846219

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Dose response, Pharmacokinetic, Efficacy, Pharmacogenetic

Cohort 1 (i.e. the main study):
Primary
• To evaluate the efficacy of 45 mg/day IMU-838 in the treatment of RRMS based on MRI assessments
Cohort 2 (i.e. the sub-study):
Primary
• To obtain more efficacy and safety data of IMU-838 in patients with RRMS and to allow pharmacodynamic modelling of the dose response.

Conditions and MedDRA coding

Relapsing-remitting multiple sclerosis

Version	Level	Code	Term	System organ class
21.1	PT	10063399	Relapsing-remitting multiple sclerosis	100000004852

Study design 6 periods

#	Title	Allocation	Blinding	Roles blinded
1	Screening period After the patient provided written informed consent, eligibility criteria will be checked and screening laboratory tests as well as a physical examination (including vital signs and electrocardiogram [ECG]) will be performed (Screening Visit 1). For eligible patients based on the assessments of Screening Visit 1, a baseline MRI (Screening Visit 2) will be performed which will serve as MRI reference for subsequent MRI assessments during the main treatment period. The quality of the baseline MRI will be evaluated by a central independent MRI reader; if the quality of the MRI is unacceptable, the baseline MRI may be repeated once per patient, and the repeated MRI will be used as baseline MRI. The central independent MRI reader will also assess the presence of Gadolinium-enhancing (Gd+) lesions as well as the number and volume of T2 lesions on the baseline MRI.	Not Applicable	None
2	IMU-838 30 mg Arm Main Treatment Period On Day 0, eligible patients will be randomized in a 1:1:1 ratio to once-daily oral treatment with 30 mg IMU-838 or 45 mg IMU-838, or placebo for 24 weeks. All patients will receive half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then start taking the full assigned dose from Day 7 onwards (2 tablets once daily). Clinic visits after Day 0 during the main treatment period will be scheduled at Day 7, and at Weeks 6, 12, 18, and 24, including trial MRI examinations at Weeks 6, 12, 18, and 24. At Week 24 (end-of-main treatment period, EoMT), patients will have the option to continue into the extended treatment period if they meet respective eligibility criteria including an MRI at Week 24.	Randomised Controlled	Double	[{"id":158247,"code":3,"name":"Monitor"},{"id":158248,"code":2,"name":"Investigator"},{"id":158246,"code":1,"name":"Subject"}]
3	IMU-838 45 mg Arm Main Treatment Period On Day 0, eligible patients will be randomized in a 1:1:1 ratio to once-daily oral treatment with 30 mg IMU-838 or 45 mg IMU-838, or placebo for 24 weeks. All patients will receive half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then start taking the full assigned dose from Day 7 onwards (2 tablets once daily). Clinic visits after Day 0 during the main treatment period will be scheduled at Day 7, and at Weeks 6, 12, 18, and 24, including trial MRI examinations at Weeks 6, 12, 18, and 24. At Week 24 (end-of-main treatment period, EoMT), patients will have the option to continue into the extended treatment period if they meet respective eligibility criteria including an MRI at Week 24.	Randomised Controlled	Double	[{"id":158251,"code":1,"name":"Subject"},{"id":158250,"code":2,"name":"Investigator"},{"id":158252,"code":3,"name":"Monitor"}]
4	Placebo Main Treatment Period On Day 0, eligible patients will be randomized in a 1:1:1 ratio to once-daily oral treatment with 30 mg IMU-838 or 45 mg IMU-838, or placebo for 24 weeks. All patients will receive half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then start taking the full assigned dose from Day 7 onwards (2 tablets once daily). Clinic visits after Day 0 during the main treatment period will be scheduled at Day 7, and at Weeks 6, 12, 18, and 24, including trial MRI examinations at Weeks 6, 12, 18, and 24. At Week 24 (end-of-main treatment period, EoMT), patients will have the option to continue into the extended treatment period if they meet respective eligibility criteria including an MRI at Week 24.	Randomised Controlled	Double	[{"id":158256,"code":2,"name":"Investigator"},{"id":158254,"code":3,"name":"Monitor"},{"id":158255,"code":1,"name":"Subject"}]
5	IMU-838 30 mg extended Treatment Period During the extended treatment period, patients were initially randomized to receive either 30 mg/day or 45 mg/day IMU-838. Patients receiving placebo will be randomized to 30 or 45 mg/day IMU-838. Patients on active treatment during the main treatment period will be randomized to continue their previous treatment assignment. Identical to the start of the main treatment period, all patients will receive half the assigned dose during the first 7 days of the extended treatment period and will then continue with the full assigned dose. Clinic visits during the extended treatment period were initially scheduled every 12 weeks and after approval of Protocol Version 4.0 will be scheduled every 24 weeks. The transition from the 12- week to 24-week schedule will be done only at the next odd-numbered visit, at which also the potential dose switch to 30 mg/day IMU-838 will occur. Until then, the 12-week schedule and the initially assigned IMU-838 dose for the OLE period still applies. After the results of the main treatment period of each cohort were made available, investigators and patients currently in the extended treatment period were unblinded and investigators received a top-line summary of trial results of the main treatment period. With approval of Protocol Version 4.0, all patients receiving 45 mg/day IMU-838 in the extended treatment period will be switched to the 30 mg dose at the next odd-numbered visit, because from results of the main treatment period of Cohort 1 together with interim Week 12 results of the Cohort 2 sub-trial it was concluded that 30 mg IMU-838 is the appropriate dose in patients with RRMS and that such dose will be used in Phase 3 trials. Patients already receiving 30 mg/day IMU-838 will continue at that dose. Switching doses to 45 mg/day IMU-838 is no longer allowed.	Not Applicable	None
6	IMU-838 45 mg extended Treatment Period During the extended treatment period, patients were initially randomized to receive either 30 mg/day or 45 mg/day IMU-838. Patients receiving placebo will be randomized to 30 or 45 mg/day IMU-838. Patients on active treatment during the main treatment period will be randomized to continue their previous treatment assignment. Identical to the start of the main treatment period, all patients will receive half the assigned dose during the first 7 days of the extended treatment period and will then continue with the full assigned dose. Clinic visits during the extended treatment period were initially scheduled every 12 weeks and after approval of Protocol Version 4.0 will be scheduled every 24 weeks. The transition from the 12- week to 24-week schedule will be done only at the next odd-numbered visit, at which also the potential dose switch to 30 mg/day IMU-838 will occur. Until then, the 12-week schedule and the initially assigned IMU-838 dose for the OLE period still applies. After the results of the main treatment period of each cohort were made available, investigators and patients currently in the extended treatment period were unblinded and investigators received a top-line summary of trial results of the main treatment period. With approval of Protocol Version 4.0, all patients receiving 45 mg/day IMU-838 in the extended treatment period will be switched to the 30 mg dose at the next odd-numbered visit, because from results of the main treatment period of Cohort 1 together with interim Week 12 results of the Cohort 2 sub-trial it was concluded that 30 mg IMU-838 is the appropriate dose in patients with RRMS and that such dose will be used in Phase 3 trials. Patients already receiving 30 mg/day IMU-838 will continue at that dose. Switching doses to 45 mg/day IMU-838 is no longer allowed.	Not Applicable	None

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

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 3

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Secondary endpoints 21

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
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
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
C1: Differences between individual treatments and between the pooled 30 mg/day and 45 mg/day groups and placebo in the following relapserelated 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
C2: Number of relapses in each treatment arm
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)
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
Safety C1+C2: AEs, serious AEs and clinically significant laboratory abnormalities (as assessed by the investigator)
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
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
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
ECG, physical examination, and vital signs
C1: Micro ribonucleic acid-122 expression (Change from Baseline to 4 hours after first dose)
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
C1+C2: Time to treatment discontinuation for any reason
C1+C2: Rate of treatment discontinuations up to Week 24
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
Pharmacodynamics C1: Changes from Baseline in lymphocyte subset parameters as measured by flow cytometry at Weeks 6 and 24 (in selected Biomarker Centers only)
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)
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)
Health outcome (C1) Treatment Satisfaction Questionnaire for Medication at Week 6, Week 24 and EoS

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

IMU-838 30 mg tablet

PRD10879486 · Product

Active substance: Vidofludimus Calcium
Pharmaceutical form: TABLET
Route of administration: ORAL USE
Max daily dose: 45 mg milligram(s)
Max total dose: 50 mg milligram(s)
Max treatment duration: 120 Month(s)
Authorisation status: Not Authorised
MA holder: IMMUNIC AG
Paediatric formulation: No
Orphan designation: No

IMU-838 22.5 mg tablet

PRD10879434 · Product

Active substance: Vidofludimus Calcium
Pharmaceutical form: TABLET
Route of administration: ORAL USE
Max daily dose: 45 mg milligram(s)
Max total dose: 50 mg milligram(s)
Max treatment duration: 120 Month(s)
Authorisation status: Not Authorised
MA holder: IMMUNIC AG
Paediatric formulation: No
Orphan designation: No

IMU-838 15 mg tablets

PRD9427315 · Product

Active substance: Vidofludimus Calcium
Pharmaceutical form: TABLET
Route of administration: ORAL USE
Max daily dose: 45 mg milligram(s)
Max total dose: 50 mg milligram(s)
Max treatment duration: 120 Month(s)
Authorisation status: Not Authorised
MA holder: IMMUNIC AG
Paediatric formulation: No
Orphan designation: No

Placebo 1

Placebo for IMU-838 Tablets

N/A · Product

Other product name: N/A
Pharmaceutical form: N/A
ATC code: N/A — N/A
Marketing authorisation: N/A
MA holder: N/A
MA country: Iceland
Paediatric formulation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Immunic AG

Sponsor organisation: Immunic AG
Address: Lochhamer Schlag 21, Lochham Lochham
City: Graefelfing
Postcode: 82166
Country: Germany

Scientific contact point

Organisation: Immunic AG
Contact name: Andreas Muehler

Public contact point

Organisation: Immunic AG
Contact name: Andreas Muehler

Third parties 19

Organisation	City, country	Duties
PharmaLex Belgium ORG-100031287	Mont-Saint-Guibert, Belgium	Code 10
MVZ Medizinisches Labor Nord MLN GmbH ORG-100045695	Hamburg, Germany	Laboratory analysis
Quanterix Corp. ORG-100044008	Billerica, United States	Laboratory analysis
WCT Worldwide Clinical Trials GER GmbH ORG-100049321	Berlin, Germany	Code 8
SCRATCH Pharmacovigilance GmbH & Co. KG ORG-100008874	Butzbach, Germany	Code 8
Siena Imaging S.r.l. ORG-100051846	Siena, Italy	Laboratory analysis
FGK Clinical Research GmbH ORG-100008669	Munich, Germany	Code 5
Clinical Trial Center S.R.L. ORG-100052323	Timisoara, Romania	On site monitoring, Code 12
MENAL Gesellschaft fuer medizinische und naturwissenschaftliche Laboranalytik mbH ORG-100044773	Emmendingen, Germany	Laboratory analysis
Dila LLC ORL-000011948	Kyiv, Ukraine	Laboratory analysis
Universitaetsklinikum Muenster AöR ORG-100006212	Muenster, Germany	Laboratory analysis
Keosys ORG-100048982	St Herblain, France	E-data capture
Verum.De GmbH ORG-100051737	Planegg, Germany	On site monitoring
IMGM Laboratories GmbH ORG-100049811	Planegg, Germany	Laboratory analysis
Anju Software Inc. ORG-100047042	Tempe, United States	Interactive response technologies (IRT), E-data capture
Resbiomed OOD ORG-100051736	Sofia, Bulgaria	On site monitoring
Neurostatus-UHB AG ORG-100046513	Basel, Switzerland	Other
Nuvisan GmbH ORG-100011873	Neu-Ulm, Germany	Laboratory analysis
GBA Central Lab Services GmbH ORG-100017343	Schwentinental, Germany	Laboratory analysis

Locations

4 EU/EEA countries · 22 investigational sites

By country

Country	MS status	Planned subjects	Sites
Bulgaria	Authorised, recruiting	57	14
Germany	Authorised, recruiting	20	1
Poland	Authorised, recruiting	60	5
Romania	Authorised, recruiting	5	2
Rest of world Ukraine	—	128	—

Investigational sites

Bulgaria

14 sites · Authorised, recruiting

Multi-profile Hospital for Active Treatment Heart and Brain EAD

Department of Neurology diseases, Pierre Curie Street 2, 5804, Pleven

Diagnostic And Consultative Center Neoclinic EAD

Department for Neurology Diseases, Bulevard Petko Yu.todorov 20, 1408, Sofiya

University Multiprofile Hospital For Active Treatment St. Ivan Rilski EAD

Clinic of Neurology Diseases, Boulevard Akademik Ivan Evstratiev Geshov 15, 1431, Sofia

Multiprofile Hospital For Active Treatment In Neurology And Psychiatry St. Naum EAD

Clinic for Intensive Care of Neurology Diseases, Clinic for Neurology Diseases for Movement Disorder, Ulitsa Dr Lyuben Rusev 1, 1113, Sofia

Multiprofile Hospital For Active Treatment In Neurology And Psychiatry St. Naum EAD

Department for Parkinson Disease, Neurology Clinic for Movement Disorders, Ulitsa Dr Lyuben Rusev 1, 1113, Sofia

University Multiprofile Hospital For Active Treatment Dr. Georgi Stranski EAD

Clinic of Neurology, Ulitsa Georgi Kochev 8a, 5803, Pleven

MBAL Sveta Marina EAD

First Neurology Clinic, Hristo Smirnenski Str 1, 9010, Varna

Military Medical Academy

Clinic of Functional Diagnostic of Nervous System, Ulitsa Sveti Georgi Sofiyski 3, 1606, Sofiya

Medical Institute Ministry Of Interior

Neurology Clinic, Bulevard Gen. Skobelev 79, 1606, Sofia

Alexandrovska University Hospital

Department of Neurodegenerative and Immunoinflammatory Diseases of the Central Nervous System, Georgy Sofiiski Str 1, 1431, Sofia

Mnogoprofilna Bolnitsa Za Aktivno Lechenie Puls AD

Department of Neurology diseases, Ulitsa Slavyanska 62, 2700, Blagoevgrad

Military Medical Academy

Clinic of Neurology Diseases, Ulitsa Sveti Georgi Sofiyski 3, 1606, Sofiya

Alexandrovska University Hospital

Clinic of Neurology Diseases, Georgy Sofiiski Str 1, 1431, Sofia

University Multiprofile Hospital For Active Treatment Kaspela EOOD

Department of Neurology Diseases, Zapaden District, Sofia Str 64, Plovdiv

Germany

1 site · Authorised, recruiting

Universitaetsklinikum Carl Gustav Carus Dresden

Zentrum für klinische Neurowissenschaften an der Neurologischen Universitätsklinik Dresden, 43 Blasewitzer Straße, EG, Dresden

Poland

5 sites · Authorised, recruiting

Neuroprotect Sp. z o.o.

Department of Clinical Research, Ul. Klaudyny 16c, 01-684, Warsaw

Medicover Integrated Clinical Services Sp. z o.o.

Private Hospital, Ul. Jana Karola Chodkiewicza 19c, 85-065, Bydgoszcz

Indywidualna Praktyka Lekarska Prof. dr hab. n. med. Konrad Rejdak

Private Practice, Ul. 1 Maja 14, 20-410, Lublin

Brg Centrum Medyczne

Private Hospital, ul. Mokra 7, 05-830, Kajetany

Neurocentrum Bydgoszcz Sp. z o.o.

MS Treatment Clinic, Ul. Aleje Prof. Sylwestra Kaliskiego 28/U1, 85-796, Bydgoszcz

Romania

2 sites · Authorised, recruiting

Elias University Emergency Hospital

Sectie Clinica Neurologie, Bulevardul Marasti 17, 011461, Bucharest

Spitalul Clinic Cai Ferate Constanta

Department of Neurologie, Bulevardul 1 Mai 5-7, 900123, Constanta

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country	Trial start	Trial end	Recruitment start	Recruitment end	Early termination
Bulgaria	2019-01-23
Germany	2022-05-30
Poland	2019-03-14
Romania	2019-08-08

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 47 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Type	Title	Version
Protocol (for publication)	D1_Protocol 2024-516739-29_fp	5.0
Protocol (for publication)	D1_Protocol 2024-516739-29_TSQM_v1-4_01May2013_fP_ro_placeholder	1.4
Protocol (for publication)	D1_Protocol 2024-516739-29_TSQM_v1-4_02Feb2012_fP_pl_placeholder	1.4
Protocol (for publication)	D1_Protocol 2024-516739-29_TSQM_v1-4_12Sep2017_fP_bg_placeholder	1.4
Protocol (for publication)	D1_Protocol 2024-516739-29_TSQM_v1-4_30Nov2022_fP_de_placeholder	1.4
Protocol (for publication)	D1_Protocol 2024-516739-29_TSQM_v1-4_30Nov2022_fP_ru_placeholder	1.4
Protocol (for publication)	D1_Protocol 2024-516739-29_TSQM_v1-4_30Nov2022_fP_ua_placeholder	1.4
Recruitment arrangements (for publication)	K1_Recruitment arrangements_Declaration	1
Recruitment arrangements (for publication)	K1_Recruitment arrangements_Declaration	1
Recruitment arrangements (for publication)	K1_Recruitment arrangements_Declaration	1
Recruitment arrangements (for publication)	K1_Recruitment arrangements_Declaration	1
Recruitment arrangements (for publication)	K2_Recruitment material_advertising leaflet_pl	3.0
Recruitment arrangements (for publication)	K2_Recruitment material_advertising website_pl	3.0
Recruitment arrangements (for publication)	K2_Recruitment material_website banner_pl	2.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Biomarker_fP_bg	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Biomarker_fP_en	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Biomarker_fP_en	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Biomarker_fP_pl	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Biomarker_fP_ro	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Genotyping_fP_bg	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Genotyping_fP_en	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Genotyping_fP_en	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Genotyping_fP_pl	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Genotyping_fP_ro	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Main Cohort2_fP_bg	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Main Cohort2_fP_en	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Main Cohort2_fP_pl	1.2
Subject information and informed consent form (for publication)	L1_SIS and ICF Main_fP_bg	4.1
Subject information and informed consent form (for publication)	L1_SIS and ICF Main_fP_de	3.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Main_fP_en	5.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Main_fP_en	4.1
Subject information and informed consent form (for publication)	L1_SIS and ICF Main_fP_pl	8.1
Subject information and informed consent form (for publication)	L1_SIS and ICF Main_fP_pl_ru	7.1
Subject information and informed consent form (for publication)	L1_SIS and ICF Main_fP_pl_ua	7.1
Subject information and informed consent form (for publication)	L1_SIS and ICF Main_fP_ro	5.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Main_fP_ro_ru	5.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Main_fP_ro_ua	5.0
Subject information and informed consent form (for publication)	L1_SIS and ICF MRI Dummy Run_fP_bg	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF MRI Dummy Run_fP_en	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF MRI Dummy Run_fP_pl	1.1
Subject information and informed consent form (for publication)	L1_SIS and ICF Pregnany follow-up_fP_de	2.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Pregnany follow-up_fP_ru	2.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Pregnany follow-up_fP_ukr	2.0
Synopsis of the protocol (for publication)	D1_Protocol synopsis lay language_2024-516739-29-00_bg	1.0
Synopsis of the protocol (for publication)	D1_Protocol synopsis lay language_2024-516739-29-00_en	1.0
Synopsis of the protocol (for publication)	D1_Protocol synopsis lay language_2024-516739-29-00_pl	1.0
Synopsis of the protocol (for publication)	D1_Protocol synopsis lay language_2024-516739-29-00_ro	1.0

Application history

4 submissions — initial application plus substantial / non-substantial modifications

#	Type	Code	Submitted	Reference MS	Conclusion	Decision date
1	INITIAL	IN	2024-08-05	Bulgaria	Acceptable 2024-09-11	2024-09-11
2	SUBSTANTIAL MODIFICATION	SM-1	2024-11-06	Bulgaria	Acceptable 2025-01-08	2025-01-09
3	NON SUBSTANTIAL MODIFICATION	NSM-1	2025-04-03	Bulgaria	Acceptable 2025-01-08	2025-04-03
4	SUBSTANTIAL MODIFICATION	SM-2	2025-11-25	Bulgaria	Acceptable 2026-03-12	2026-03-13