Trial document




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  DRKS00014034

Trial Description

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Title

Prospective study to validate a multidimensional treatment decision score (DIFUTURE-MS-TDS) which predicts the 24 month outcome in untreated patients with Clinically Isolated Syndrome and early Relapsing-Remitting Multiple Sclerosis under specific treatment options

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Trial Acronym

ProVal-MS

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URL of the Trial

[---]*

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Brief Summary in Lay Language

Background:
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system affecting almost 1 million people in Europe. Current drugs approved for treatment of relapsing-remitting type of multiple sclerosis (RRMS), can be grouped as 1-moderately effective but safe and 2-highly active but potentially with severe side effects. Abstaining from any treatment may also be an option for the patient. Since the course of disease currently cannot be predicted at time of diagnosis some patients with benign disease may be exposed to long-term harmful treatment while effective treatment may be delayed for years in patients with a more aggressive disease. For this reason characteristics are needed to predict the course of the disease upon diagnosis that allows an early, personalized treatment decision.

Study Population:
Patients aged 18 – 60 years and newly diagnosed with clinically isolated syndrome (CIS) or RRMS during the last 2 years and before the initiation of any immunotherapy.

Primary Objective:
To test the discriminatory ability of a treatment decision score on the 24 months outcome in RRMS and CIS patients. Success at month 24 is defined as no new lesions, indicative of inflammation, in magnetic resonance images (MRI) between month 6 and 24.

Treatment:
This is an observational study so treatment decisions are under the responsibility of the treating physicians and have to follow state of the art best-practice rules.

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Brief Summary in Scientific Language

ProVal-MS is a multi-center prospective cohort study on MS within the DIFUTURE consortium. The main objective of the ProVal-MS is to prospectively validate the clinical potential of the novel personalised medicine approaches for MS patients provided by DIFUTURE-MS-TDS score in a diagnostic Phase II study. Diagnostic Phase II studies are defined as: Determining the diagnostic accuracy (discrimination, calibration) through case-control studies. In this study cases will be the patients with evidence of an unfavorable outcome at month 24, controls are those patients with a favorable outcome at month 24. It is expected that the outcome is more favorable for patients for whom predicted and received therapy agree. Therefore, cases and controls are both drawn from within the prospective ProVal-MS study, a design that is referred to as a case-control study nested into a cohort study

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Organizational Data

  •   DRKS00014034
  •   2018/12/21
  •   [---]*
  •   yes
  •   Approved
  •   323/18 S, Ethik-Kommission der Fakultät für Medizin der Technischen Universität München
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Secondary IDs

  • [---]*
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Health Condition or Problem studied

  •   G35.0 -  [generalization G35: Multiple sclerosis]
  •   G35.1 -  [generalization G35: Multiple sclerosis]
  •   G35.9 -  [generalization G35: Multiple sclerosis]
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Interventions/Observational Groups

  •   Controls: Patients with success at month 24 defined as no new T2-lesions in sMRT and cMRT between month 6 and 24.
  •   Cases: Patients with no success at month 24 defined as new T2-lesions in sMRT and cMRT between month 6 and 24.
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Characteristics

  •   Non-interventional
  •   Observational study
  •   Other
  •   Open (masking not used)
  •   [---]*
  •   Other
  •   Prognosis
  •   Other
  •   II
  •   N/A
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Primary Outcome

AUC of the ROC based on the DIFUTURE-MS-TDS score and diseases status at 24 months after start of treatment

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Secondary Outcome

Using a calibration curve to assess calibration for the DIFUTRE-MS-TDS score.
Summarizing predictive quality of DIFUTRE-MS-TDS by its Brier Score.
Explorative analyses on the predictive relevance of biomarkers for treatment success. Explore predictive value of the DIFUTURE-MS-TDS score on the secondary clinical and paraclinical endpoints.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
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Recruitment

  •   Actual
  •   2019/03/06
  •   250
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   60   Years
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Additional Inclusion Criteria

I 1. Male and female patients between the age of 18 and 60 years with CIS or RR-MS according to the valid 2017 McDonald criteria diagnosed within the last two years and before the initiation of immunotherapy
I 2. Having given written informed consent prior to undertaking any study-related procedures

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Exclusion Criteria

Patients who have met all the above inclusion criteria will be screened for the following exclusion criteria:
E 01.Under any administrative or legal supervision or unable to give informed consent.
E 02.Previous treatment with DMT drugs (including corticosteroid therapy of relapses if given less than four weeks prior baseline)
E 03.Conditions/situations such as:
oPatients with conditions/concomitant diseases making them non-evaluable for the primary endpoint (e.g. pre-existing neurological disease, systemic autoimmune diseases)

oA requirement for concomitant treatment that could bias primary evaluation

oThe inability to meet specific protocol requirements (e.g., need for hospitalization, not able to read and understand the informed consent form)

oThe patient is directly involved in the conduct of the protocol: the investigator or a subinvestigator, research assistant, pharmacist, study coordinator, other staff or relative thereof

oIs uncooperative or has any condition that could make the patient potentially non-compliant to the study procedures

oPregnant or breast-feeding women

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Addresses

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    • Neurologische Klinik, Klinikum rechts der Isar, TU München
    • Mr.  Univ. Prof. Dr  Bernhard  Hemmer 
    • Ismaninger Str. 22
    • 81675  München
    • Germany
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    •   +49-89-4140-4601
    •   +49-89-4140-7681
    •   hemmer at tum.de
    •   [---]*
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    • Neurologische Klinik, Klinikum rechts der Isar, TU München
    • Mr.  Univ. Prof. Dr  Bernhard  Hemmer 
    • Ismaninger Str. 22
    • 81675  München
    • Germany
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    •   +49-89-4140-4601
    •   +49-89-4140-7681
    •   hemmer at tum.de
    •   [---]*
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    • Neurologische Klinik, Klinikum rechts der Isar, TU München
    • Mr.  Univ. Prof. Dr  Bernhard  Hemmer 
    • Ismaninger Str. 22
    • 81675  München
    • Germany
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    •   +49-89-4140-4601
    •   +49-89-4140-7681
    •   hemmer at tum.de
    •   [---]*
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    • Neurologische UniversitätsklinikUniversitätsklinikum Tübingen
    • Mr.  Univ. Prof.  Ulf  Ziemann 
    • Hoppe-Seyler-Straße 3
    • 72076  Tübingen
    • Germany
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    • Klinik für Neurologie, KUMForschungseinheit Therapieforschung
    • Mr.  Uni. Prof.  Martin  Kerschensteiner 
    • Marcioninistr 15
    • 81377  München
    • Germany
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    • Neurologische Klinik und Klinische Neurophysiologie, Klinikum Augsburg
    • Mr.  PD Dr. med.  Antonios  Bayas 
    • Stenglinstr 2
    • 86156  Augsburg
    • Germany
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    • Neurologische Klinik und Klinische Neurophysiologie, Klinikum Augsburg
    • Mr.  Prof. Dr. med  Markus  Naumann 
    • Stenglinstr 2
    • 86156  Augsburg
    • Germany
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Sources of Monetary or Material Support

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    • Bundesministerium für Bildung und Forschung
    • Heinemannstr. 2
    • 53175  Bonn
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.