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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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03193866
Recruitment Status : Active, not recruiting
First Posted : June 21, 2017
Last Update Posted : March 13, 2020
Sponsor:
Collaborators:
Patient-Centered Outcomes Research Institute
Kaiser Foundation Research Institute
Information provided by (Responsible Party):
Fredrik Piehl, Karolinska Institutet

Tracking Information
First Submitted Date April 20, 2017
First Posted Date June 21, 2017
Last Update Posted Date March 13, 2020
Actual Study Start Date February 1, 2017
Estimated Primary Completion Date June 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 18, 2017)
  • 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
  • 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
  • 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)
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: June 18, 2017)
  • 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
  • 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
  • Annual relapse rate [ Time Frame: 3-9 years ]
    - Comparison of mean number of relapses per year between the different treatments
  • Number of Contrast-enhancing lesions (CEL) [ Time Frame: 3-9 years ]
    - Comparison of mean number of CEL on yearly MRI between the different treatments
  • Increase in EDSS [ Time Frame: 3-9 years ]
    - Comparison of yearly increase in mean and median EDSS between the different treatments
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Treatment satisfaction [ Time Frame: 3-9 years ]
    Comparison of patient satisfaction with their treatment using the Treatment Satisfaction Questionnaire (TSQ) between the treatments
  • Quality of life [ Time Frame: 3-9 years ]
    - Comparison of health related QoL measured by EQ-5D between the treatments
  • Fatigue [ Time Frame: 3-9 years ]
    Comparison of fatigue measured by the Fatigue Scale for Motor and Cognitive Functions (FSMC) between the treatments
  • Health economy [ Time Frame: 3-9 years ]
    - Estimation of total societal costs per year after initiating treatment
  • Occurrence of Anti-drug antibodies (ADA) [ Time Frame: 3-9 years ]
    - Proportion of patients treated with RTX developing high-titer anti-RTX ADA
  • Employment rate [ Time Frame: 3-9 years ]
    - Comparison of mean number of working hours per week between the treatments.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title COMparison Between All immunoTherapies for Multiple Sclerosis.
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
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).
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).

Study Type Observational [Patient Registry]
Study Design Observational Model: Cohort
Time Perspective: Other
Target Follow-Up Duration 3 Years
Biospecimen Retention:   Samples Without DNA
Description:
Serum samples will be taken yearly for analysis of anti-drug antibodies. These samples will be saved in biobank.
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.
Condition Relapsing-remitting Multiple Sclerosis
Intervention 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
Study Groups/Cohorts Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Active, not recruiting
Actual Enrollment
 (submitted: March 12, 2020)
3526
Original Estimated Enrollment
 (submitted: June 18, 2017)
3700
Estimated Study Completion Date December 31, 2022
Estimated Primary Completion Date June 30, 2022   (Final data collection date for primary outcome measure)
Eligibility 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

Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Sweden
Removed Location Countries  
 
Administrative Information
NCT Number NCT03193866
Other Study ID Numbers COMBAT-MS
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Fredrik Piehl, Karolinska Institutet
Study Sponsor Karolinska Institutet
Collaborators
  • Patient-Centered Outcomes Research Institute
  • Kaiser Foundation Research Institute
Investigators
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
PRS Account Karolinska Institutet
Verification Date March 2020