Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    COMBAT-MS
Previous Study | Return to List | Next Study

COMparison Between All immunoTherapies for Multiple Sclerosis. (COMBAT-MS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03193866
Recruitment Status : Recruiting
First Posted : June 21, 2017
Last Update Posted : April 3, 2018
Sponsor:
Collaborators:
Patient-Centered Outcomes Research Institute
Kaiser Foundation Research Institute
Information provided by (Responsible Party):
Fredrik Piehl, Karolinska Institutet

Brief Summary:
The overarching goal of this study is to determine whether rituximab (RTX) offers effectiveness and safety advantages over other commonly used approved Disease-Modifying Drugs (DMT) in the largest real-world population-based structured prospective follow-up cohort of Relapsing-Remitting Multiple Sclerosis (RRMS) patients. The study will include both treatment naïve patients starting their first DMT and patients switching from a previous first line DMT (escalation/second-line).

Condition or disease Intervention/treatment
Relapsing-remitting Multiple Sclerosis Drug: Rituximab

Detailed Description:

This is a prospective non-intervention observational prospective cohort study assessing the long-term safety and efficacy of RTX treatment in MS compared with other common MS DMTs regarding both clinical and radiological parameters in a real-life population of patients with MS.

A number of parameters will be assessed annually. These include baseline demographics, previous drug history and reasons for discontinuation, disability status (expanded disability status scale), relapses, safety and adverse events (AE), contrast enhancing T1 and newly appearing T2 lesions on magnetic resonance imaging, as well as a panel of patient reported outcome measures: Symbol Digit Modalities Test (SDMT); MS impact scale-29 (MSIS-29) Fatigue Scale for Motor and Cognitive Functions (FSMC), EuroQol-5 Dimensions (EQ-5D), the MS check scale and Treatment Satisfaction Questionnaire 9 (TSQM-9).

Retrospective data entered in medical charts and the Swedish MS registry will be included together with prospective annual structured follow up from inclusion into the study for a minimum of three years (three to nine years).


Layout table for study information
Study Type : Observational [Patient Registry]
Estimated Enrollment : 3700 participants
Observational Model: Cohort
Time Perspective: Other
Target Follow-Up Duration: 3 Years
Official Title: COMparison Between All immunoTherapies for Multiple Sclerosis. An Observational Long-term Prospective Cohort Study of Safety, Efficacy and Patient's Satisfaction of MS Disease Modulatory Treatments in Relapsing-remitting Multiple Sclerosis
Actual Study Start Date : February 1, 2017
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Rituximab


Intervention Details:
  • Drug: Rituximab
    Comparisons of efficacy and safety between rituximab and all other frequently used immunomodulating drugs against multiple sclerosis
    Other Names:
    • Natalizumab
    • Fingolimod
    • Alemtuzumab
    • Interferon-beta
    • Glatiramer acetate
    • Dimethyl Fumarate


Primary Outcome Measures :
  1. Confirmed disease progression in patients with Expanded Disability Status Scale (EDSS) ≤2.5 at baseline [ Time Frame: 3 years ]
    - Proportion of patients with baseline EDSS ≤2.5 progressing to 12 months confirmed EDSS ≥3 among those over 3 years of follow up

  2. Confirmed disease progression in patients with EDSS ≥2.5 at baseline [ Time Frame: 3 years ]
    - Proportion of patients with baseline EDSS ≥2.5 experiencing 6 months confirmed EDSS increase of 1 point among those over 3 years of follow up

  3. Disease-related impact on daily life [ Time Frame: 3 years ]
    - Change in MSIS-29 over 3 years of follow up (change from baseline; mean value ±SD)


Secondary Outcome Measures :
  1. Safety [ Time Frame: 3-9 years ]
    - Rate of malignancy, cardiovascular disease, serious infections and all-cause mortality in populations on therapy and ever treated, respectively

  2. Occurence of Serious Adverse Reactions [ Time Frame: 3-9 years ]
    - The occurrence of serious adverse events (SAE) of all types that are possibly or likely related to DMT treatment

  3. Annual relapse rate [ Time Frame: 3-9 years ]
    - Comparison of mean number of relapses per year between the different treatments

  4. Number of Contrast-enhancing lesions (CEL) [ Time Frame: 3-9 years ]
    - Comparison of mean number of CEL on yearly MRI between the different treatments

  5. Increase in EDSS [ Time Frame: 3-9 years ]
    - Comparison of yearly increase in mean and median EDSS between the different treatments

  6. Proportion of patients with at least 1 step increase in EDSS [ Time Frame: 3-9 years ]
    - Comparison of yearly proportion of patients with at least 1 step increase in EDSS between the different treatments

  7. Proportion of patients with No Evidence of Disease Activity (NEDA) -2 [ Time Frame: 3-9 years ]
    - Comparison of early proportion of patients with No Evidence of Disease Activity (NEDA) -2 (free of exacerbations, new/enlarged T2-lesions and occurrence of CEL) between the treatments

  8. Proportion of patients with NEDA-3 [ Time Frame: 3-9 years ]
    - Comparison of early proportion of patients with NEDA-3 (NEDA-2 plus no worsening of EDSS from baseline) between the treatments

  9. Levels of Neurofilament-Light chain (NFL) in serum [ Time Frame: 3-9 years ]
    - Comparison of mean levels of Neurofilament-Light chain (NFL) in serum between the different treatments

  10. Brain atrophy rate [ Time Frame: 3-9 years ]
    - Comparison of yearly brain atrophy rate measured as per cent brain parenchymal fraction (BPF) loss in relation to baseline values between the different treatments

  11. Time on drug [ Time Frame: 3-9 years ]
    - Comparison of time to drug discontinuation between the different treatments. Separate analyses will be performed depending on reason to drug discontinuation, mainly side effects and lack of efficacy

  12. Treatment satisfaction [ Time Frame: 3-9 years ]
    Comparison of patient satisfaction with their treatment using the Treatment Satisfaction Questionnaire (TSQ) between the treatments

  13. Quality of life [ Time Frame: 3-9 years ]
    - Comparison of health related QoL measured by EQ-5D between the treatments

  14. Fatigue [ Time Frame: 3-9 years ]
    Comparison of fatigue measured by the Fatigue Scale for Motor and Cognitive Functions (FSMC) between the treatments

  15. Health economy [ Time Frame: 3-9 years ]
    - Estimation of total societal costs per year after initiating treatment

  16. Occurrence of Anti-drug antibodies (ADA) [ Time Frame: 3-9 years ]
    - Proportion of patients treated with RTX developing high-titer anti-RTX ADA

  17. Employment rate [ Time Frame: 3-9 years ]
    - Comparison of mean number of working hours per week between the treatments.


Biospecimen Retention:   Samples Without DNA
Serum samples will be taken yearly for analysis of anti-drug antibodies. These samples will be saved in biobank.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
All patients initiated at their first or second disease-modifying drug between January 1 2011 and June 30 2018 will be included in the trial. Up to present date, study-related data will be retrospectively controlled via individual study of patient records. Patients will be identified through the Swedish MS registry. Inclusion into the COMBAT-MS core study will be subject to written informed consent. Given the non-intervention design of the study and very limited study-specific procedures outside of clinical practise, we expect participation rates to be very high. Based on preliminary calculations from the MS registry the projected number of participants will be 3700 patients, out of which at least 1000 are treated with rituximab first or second-line.
Criteria

INCLUSION CRITERIA:

The study population consists of all patients with Clinically Isolated Syndrome (CIS) or RRMS who;

  • Initiate a first MS DMT (treatment naïve), or Initiate a second ever DMT, of a different drug class than the first, regardless of time between drugs or reason for discontinuation("switchers") from 1st Jan 2011 to 30st June 2018, and
  • Are followed at any of the University clinics of Sweden, and
  • Consent to participation in COMBAT-MS core, and
  • Are expected to be capable to follow study assessments.

EXCLUSION CRITERIA:

- Patients with progressive forms of MS at start of therapy are not eligible


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03193866


Contacts
Layout table for location contacts
Contact: Fredrik Piehl, Professor +46 73-671 81 01 Fredrik.Piehl@ki.se

Locations
Layout table for location information
Sweden
Fredrik Piehl Recruiting
Stockholm, Sweden
Contact: Fredrik Piehl, Professor    +46 73-671 81 01    Fredrik.Piehl@ki.se   
Contact: Anna Fogdell-Hahn, PhD    +46 70-544 90 60    anna.fogdell-hahn@ki.se   
Sponsors and Collaborators
Karolinska Institutet
Patient-Centered Outcomes Research Institute
Kaiser Foundation Research Institute
Investigators
Layout table for investigator information
Principal Investigator: Fredrik Piehl, MD, PhD Karolinska Institutet, Stockholm, Sweden
Principal Investigator: Anders Svenningsson, MD, PhD Karolinska Institutet, Stockholm, Sweden
Principal Investigator: Anna Fogdell-Hahn, PhD Karolinska Institutet, Stockholm, Sweden
Principal Investigator: Ingrid Kockum, PhD Karolinska Institutet, Stockholm, Sweden
Principal Investigator: Thomas Frisell, PhD Karolinska Institutet, Stockholm, Sweden
Principal Investigator: Annette Langer-Gould, MD, PhD Kaiser Permanent Southern California, Los Angeles, USA

Additional Information:

Layout table for additonal information
Responsible Party: Fredrik Piehl, Professor, Karolinska Institutet
ClinicalTrials.gov Identifier: NCT03193866     History of Changes
Other Study ID Numbers: COMBAT-MS
First Posted: June 21, 2017    Key Record Dates
Last Update Posted: April 3, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Fredrik Piehl, Karolinska Institutet:
Immunomodulating treatment
Cohort study
Dimethyl fumarate
Fingolimod
Interferon-beta
Natalizumab
Rituximab
Glatiramer acetate

Additional relevant MeSH terms:
Layout table for MeSH terms
Sclerosis
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Rituximab
Interferon-beta
Natalizumab
Fingolimod Hydrochloride
Glatiramer Acetate
(T,G)-A-L
Dimethyl Fumarate
Interferons
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Adjuvants, Immunologic
Dermatologic Agents