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TMP001 in Relapsing-remitting Multiple Sclerosis

Phase 2
Completed
Conditions
Remitting-Relapsing Multiple Sclerosis
Interventions
Registration Number
NCT02686788
Lead Sponsor
Dr. Frank Behrens
Brief Summary

The purpose of this study is to assess the impact of TMP001 in the treatment of patients with relapsing-remitting multiple sclerosis (RRMS). Therefore the average total number of contrast enhancing lesions (CELs) on brain MRI scans at weeks 12, 16, 20, and 24 during treatment with TMP001 is compared to the average total number of CELs on brain MRI scans at week -4 and baseline in these patients .

Based on promising preclinical results, the investigators assume a comparable effect of TMP001 on reduction of contrast-enhancing lesions as shown for other immunomodulatory substances in recent clinical studies.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
9
Inclusion Criteria
  • Age 18 to 55 years
  • Definite diagnosis of RRMS (according to revised McDonald criteria, Polman et al. 2011, Annals of Neurology 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 screening (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
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. gadopentetate-dimeglumine)
  • 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)

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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
TMP001TMP001600mg TMP001 as gelatine capsules á 200mg taken orally twice per day for a duration of 24 weeks
Primary Outcome Measures
NameTimeMethod
Comparison of average total number of contrast enhancing lesionsat week -4, week 0 (baseline), week 4, 8, 12, 16, 20 and 24

Comparison of average total number of contrast enhancing lesions (CELs) on Brain MRI scans at weeks 4, 8, 12, 16, 20 and 24 as compared to the average total number of CELs on brain MRI scans at week -4 and baseline (BL)

Secondary Outcome Measures
NameTimeMethod
Comparison of average total volume of contrast enhancing lesionsat week -4, week 0 (baseline), week 4, 8, 12, 16, 20 and 24

Average total volume of CELs (in mm3) on brain MRI scans at week 4,8, 12, 16, 20 and 24 as compared to the average total CEL volume on brain MRI scans at week -4 and BL

Comparison of T2- hyperintense lesions as assessed in MRIat week 0 (baseline) and week 24

New or enlarged T2- hyperintense lesions at week 24 as compared to baseline - Number and Characteristics of T2-hyperintense leasion as to be found in MRI Assessment in Comparison between baseline and week 24

Comparison of T1-hypointense lesions as assessed in MRIat week 0 (baseline) and week 24

New T1-hypointense lesions at week 24 as compared to baseline as to be found in MRI Assessment in Comparison between baseline and week 24

relapse rateweek -4 until week 24

Documentation of any replapse during study period to determine the annualised relapse rate

Assessment of Lipid profile at different time pointsat week 0 (baseline), week 12 and 24

Concentration of a variety of lipids will be determined at weeks 12 and 24 and described in comparison to the lipid profile at baseline

Pain questionnaireat week 0 (baseline), week 12 and week 24

Pain questionnaire at BL, week 12 and week 24

TMP001-concentrationsweek 4, 8, 12, 16, 20 and 24

Assessment of TMP001-concentrations

Expanded disability status scale (EDSS)at week 0 (baseline), week 12 and 24

EDSS at weeks 12 and 24 as compared to baseline

Trial Locations

Locations (5)

Universitätsklinikum Heidelberg Neurologische Klinik

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Heidelberg, Germany

UKT, Universitätsklinikum Tübingen

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Tübingen, Baden-Würtemberg, Germany

Goethe-Universität Frankfurt am Main

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Frankfurt am Main, Hessen, Germany

Universitätsklinikum Münster, Klinik für Allgemeine Neurologie

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Münster, Nordrhein-Westfalen, Germany

Charite- Universitätsmedizin Berlin (Campus Mitte) NeuroCure Clinical Research Center NCRC AG Klinische Neuroimmunologie

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Berlin, Germany

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