Patients with defined diagnosis of relapsing-remitting multiple sclerosis and at least 1 documented relapse during the previous year OR at least 2 documented relapses during the previous 2 years. MedDRA version: 19.0 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: Tarenflurbil
Product Code: TMP001
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Tarenflurbil
CAS Number: 5104-49-4
Other descriptive name: FLURBIPROFEN
Concentration unit: mg m
Sponsors
Fraunhofer Gesellschaft for its Institute Fraunhofer Institute for Molecular Biology and Applied Ecology (IME)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age 18 to 55 years • Definite diagnosis of RRMS (according to revised McDonald criteria, Polman et al. 2011, Ann Neurol 69:292-302) • At least 1 documented relapse during the previous year OR at least 2 documented relapses during the previous 2 years • At least one contrast-enhancing lesion (CEL) on the screening MRI scan at week -4 • EDSS of 0 – 5 (inclusive) at screeing (week -4) • Women of childbearing potential (WOCBP) must use 2 adequate forms of contraception to avoid pregnancy throughout the trial (such as a double barrier method) and for up to 8 weeks after the last dose of TMP001 in such a manner that the risk of pregnancy is minimized • Written informed consent obtained prior to the initiation of any protocol-required procedures • Compliance to study procedure and study protocol Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 55 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • History of chronic disease of the immune system other than MS or a known immunodeficiency syndrome • Clinically severe active infection (e.g., pneumonia, septicaemia) within the 1 month prior to Screening. • Diagnosis of neuromyelitis optica, clinically isolated syndrome, secondary progressive multiple sclerosis, or primary progressive multiple sclerosis • History of drug or alcohol abuse within 2 years of inclusion to the study • Relapse or corticosteroid treatment within 30 days before screening (week -4) • Interferon-beta, glatiramer acetate, teriflunomide, dimethyl fumarate or fingolimod therapy had to have been stopped 3 or more months before enrolment • Immunosuppressive medication such as azathioprine or methotrexate, Ciclosporin, cyclophosphamide, mycophenolate mofetil, mitoxantrone or cladribine at any time • Any previous therapy with alemtuzumab, ocrelizumab, ofatumumab, rituximab, belimumab, natalizumab, total body irradiation, or bone marrow transplantation • Any investigational drug or placebo within 12 weeks prior to enrolment OR > 5 half-lives prior to screening (week -4), whichever is longer • Women that are pregnant or currently breast feeding • Concurrent participation in other clinical trials • History of, or current diagnosis of, malignancy (including previously treated skin cancer other than successfully treated basal and squamous skin cancer with no evidence of recurrence within 5 years) • Inability to complete an MRI or contraindications for MRI, including but not limited to claustrophobia, presence of a pacemaker, cochlear implants, ferromagnetic devices or clips, intracranial vascular clips, insulin pumps, or nerve stimulators • Hypersensitivity to contrast agent (Gadolinium, resp. Gadopentetat-Dimeglumin) • Any reason in the discretion of the investigator regarding the safe participation of the patient in the study or for any other reason, the investigator considers the patient inappropriate for participation in the study. • White blood count (WBC) <3000 mm3 at screening (week -4) • Lymphocytes < 800 mm3 at screening (week -4) • Known renal insufficiency stage III or higher (eGFR = 59ml/min/1.73 m2; according to the Kidney Disease Outcomes Quality Initiative (KDOQI)) Exclusion criteria regarding the study medication: • Patients with known hypersensitivity to study medication • Patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) • Patients with a history of peptic ulcer disease and/or gastrointestinal bleeding • Chronic or acute renal, hepatic or metabolic disorder •Patients with a history of myocardial infarction, ischemic stroke or known heart failure •Patients with known thrombophilia or abnormal clinically significant coagulation parameter at screening (week -4)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Average total number of contrast enhancing lesions (CELs) on brain MRI scans at weeks 12, 16, 20, and 24 compared to the average total number of CELs on brain MRI scans at week -4 and baseline (BL).;Secondary Objective: - Average total volume of CELs (in mm3) on brain MRI scans at week 12, 16, 20 and 24 compared to the average CEL volume on brain MRI at week -4 and baseline (BL) - New or enlarged T2-hyperintense lesions at week 24 as compared to BL - New T1-hypointense lesions at week 24 as compared to BL - Annualised relapse rate - EDSS at week 12 and 24 as compared to BL - Lipid profile at week 12 and 24 as compared to BL - Assessment of TMP001-concentrations - Pain questionnaire at BL, week 12 and week 24 ;Primary end point(s): Primary endpoint efficacy: - Average total number of contrast enhancing lesions (CELs) on brain MRI scans at week 12, 16, 20 and 24 as compared to the average total number of CELs on brain MRI scans at week -4 and week 0 (baseline);Timepoint(s) of evaluation of this end point: week -4, week 0 (baseline), 12, 16, 20, and 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints efficacy: - Average total volume of CELs (in mm3) on brain MRI scans at week 12, 16, 20 and 24 as compared to the average CEL volume on brain MRI scans at week -4 and week 0 (baseline) - New or enlarged T2-hyperintense lesions at week 24 compared to baseline - New T1-hypointense lesions at week 24 as compared to baseline - annualised relapse rate - EDSS at week 12 and 24 as compared to baseline - Lipid profile at week 12 and 24 as compared to baseline - Assessment of TMP001-concentrations - Pain questionnaire at baseline, week 12 and week 24 Main parameters of safety: - haematology, blood chemistry and urinanalysis every 4 weeks - intracellular cytokine profiles - incidence and severity of AEs;Timepoint(s) of evaluation of this end point: week -4, week 0 (baseline), 12, 16, 20, and 24 | — |
Countries
Germany
Contacts
Public ContactProject group TMP
Fraunhofer IME, Clinical Research
Outcome results
None listed