Clinical trial NCT02686788: TMP001 in Relapsing-remitting Multiple Sclerosis
Official title: TMP001 in Relapsing-remitting Multiple Sclerosis: A Multicentre Open, Baseline-controlled Phase IIa Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Remitting-Relapsing Multiple Sclerosis
Keywords: multiple sclerosis
relapsing remitting
nonsteroidal anti-inflammatory drug
contrast enhancing lesions
Lead sponsor: Fraunhofer Institute for Translational Medicine and Pharmacology ITMP
Sponsor class: OTHER
Collaborators: name: SocraMetrics GmbH
First posted: 2016-02-22
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Comparison of average total number of contrast enhancing lesions
timeFrame: at week -4, week 0 (baseline), week 4, 8, 12, 16, 20 and 24
Secondary outcomes:
measure: Comparison of average total volume of contrast enhancing lesions
timeFrame: at week -4, week 0 (baseline), week 4, 8, 12, 16, 20 and 24
measure: Comparison of T2- hyperintense lesions as assessed in MRI
timeFrame: at week 0 (baseline) and week 24
measure: Comparison of T1-hypointense lesions as assessed in MRI
timeFrame: at week 0 (baseline) and week 24
measure: relapse rate
timeFrame: week -4 until week 24
measure: Expanded disability status scale (EDSS)
timeFrame: at week 0 (baseline), week 12 and 24
measure: Assessment of Lipid profile at different time points
timeFrame: at week 0 (baseline), week 12 and 24
measure: TMP001-concentrations
timeFrame: week 4, 8, 12, 16, 20 and 24
measure: Pain questionnaire
timeFrame: at week 0 (baseline), week 12 and week 24
Other outcomes:
Locations:
city: Tübingen
country: Germany
facility: UKT, Universitätsklinikum Tübingen
state: Baden-Würtemberg
city: Frankfurt am Main
country: Germany
facility: Goethe-Universität Frankfurt am Main
state: Hessen
city: Münster
country: Germany
facility: Universitätsklinikum Münster, Klinik für Allgemeine Neurologie
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Charite- Universitätsmedizin Berlin (Campus Mitte) NeuroCure Clinical Research Center NCRC AG Klinische Neuroimmunologie
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg Neurologische Klinik
Study officials:
affiliation: University Department of Neurology Tübingen
name: Ulf Ziemann, MD
role: PRINCIPAL_INVESTIGATOR
References: