Discontinuation of Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS): Extension of the DISCOMS Study

NCT04754542 | Completed Results

• 1 other identifier: 20-2772
• Study Type: observational
• Target: 76
• Locations: 1 country
• Sites: 10

Brief Summary

The Main Hypothesis of this extension trial is that among those who have successfully discontinued their DMT as part of the DISCOMS trial (i.e. did not have a new MS relapse or brain MRI lesion) and remain off DMT after DISCOMS are at no greater risk of new or worsened MS disease activity compared to those who successfully continued their DMT as part of DISCOMS and remain on DMT, each assessed at least one year after termination of the primary DISCOMS study.

Conditions

Multiple Sclerosis

Keywords

Discontinuation; MS; DMT; Medication; Extension

Outcome Measures

Primary Outcomes (1)

• Number of Participants Off Drug That Have New Inflammatory Disease Compared to Those on Drug.

  As inflammatory disease activity may be manifested clinically as a relapse, or radiographically as a new MRI lesion, we have chosen a combined primary outcome measure.

  Month 36 visit. The Month 36 visit was the extension study's only visit, which occurred 36 months after randomization in the original DISCOMS study (NCT03073603).

Secondary Outcomes (1)

• Compare the Change in Disability Using the EDSS Over the Duration of the Trial in Those Who Were Able to Maintain Their Treatment Assignment Without Inflammatory Activity.

  Baseline of the original DISCOMS study (NCT03073603) and Month 36. The Month 36 visit was the extension study's only visit, which occurred 36 months after randomization in the original DISCOMS study.

Other Outcomes (21)

• Change in Patient Reported Outcomes (PROs) - NeuroQoL Short Form Scores -- Upper Extremity Function

  Baseline of the original DISCOMS study (NCT03073603) and Month 36. The Month 36 visit was the extension study's only visit, which occurred 36 months after randomization in the original DISCOMS study.

• Change in Patient Reported Outcomes (PROs) - NeuroQoL Short Form Scores -- Lower Extremity Function

  Baseline of the original DISCOMS study (NCT03073603) and Month 36. The Month 36 visit was the extension study's only visit, which occurred 36 months after randomization in the original DISCOMS study.

• Change in Patient Reported Outcomes (PROs) - NeuroQoL Short Form Scores -- Fatigue

  Baseline of the original DISCOMS study (NCT03073603) and Month 36. The Month 36 visit was the extension study's only visit, which occurred 36 months after randomization in the original DISCOMS study.

Study Arms (2)

Discontinuation

This study is only observing participants that received an intervention from a previous study. Participants that were randomized to discontinue their disease modifying therapy (DMT) in the DISCOMS study and consent to this extension trial will remain in this arm for the extension.

Continuation

This study is only observing participants that received an intervention from a previous study. Participants that were randomized to continue their disease modifying therapy (DMT) in the DISCOMS study and consent to this extension trial will remain in this arm for the extension.

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study population is limited to subjects that are currently participating in or have completed the DISCOMS trial (NCT# 03073603). Only subjects that remained in their original treatment arm throughout the trial as well as those that remained in their treatment arm after their participation was completed will qualify. Participants in the DISCOMS trial that experienced a relapse during the study will not qualify for the extension.

You may qualify if:

• Participation in and completion of the DISCOMS trial (NCT# 03073603) for a minimum of 18 and maximum of 24 months (i.e., it is possible some will have been enrolled late enough in the primary study so as to not have completed the full 24 months).
• o Only include participants in the following study groups
• Randomized to the discontinue group, stayed off their DMT throughout and after the trial
• Randomized to the continue group, continuously\* stayed on their DMT throughout and after the trial
• Must be willing to continue in their previously-assigned treatment group for the entire, additional 12-Month follow-up period. For those in the continue group, the participant may have switched to a generic or biosimilar version of their medication, or to a different approved medication, if due to intolerance, convenience or insurance mandates, but NOT if due to having new or worsening MS disease activity.
• RRMS, SPMS, or PPMS by McDonald 2010 criteria. Patients will be defined by subtype based on 2013 updated phenotypic criteria. Progression of MS will be defined by the local principal investigator either prospectively with an EDSS change of at least 1.0 points over the last two years, or retrospectively, with any significant change in motor function over at least one year, unrelated to relapse.
• During the primary DISCOMS study, no evidence of recent new inflammatory disease activity (inactive by the Lublin criteria). Pseudorelapses due to infection, fever, or other stressors as deemed by the local PI will NOT be excluded. Those who have already successfully completed the primary DISCOMS study without having a new relapse or MRI scan change, but who have a relapse or scan change AFTER ending participation in DISCOMS but before entering the extension ARE eligible and will be recruited, i.e. we do not wish to undercount new activity that occurs after exiting DISCOMS.
• Provides informed consent to continue in the extension trial.
• Willing to follow the protocol.
• Able to undergo a brain MRI without anesthesia, as part of routine care (i.e. paid for by their insurance).
• Continuously will be defined as no less than 75% of all prescribed doses, with no time of greater than four weeks from last intended dose to have missed a dose (8 weeks for natalizumab, i.e. one missed dose).

You may not qualify if:

• During original DISCOMS trial participant was randomized to the discontinue group, but then either re-started their DMT during the trial (study-defined 'treatment withdrawal), or wishes to restart their DMT after completing original DISCOMS study. Conversely, also excluded are those who completed the primary trial in the continue group and then discontinued, or wishes to discontinue, after completion of the primary study.
• Any MS relapse or new MRI scan lesion (3 mm or larger) during the primary DISCOMS trial, with relapse determined by the blinded examiner and MRI lesion determined by the blinded MRI reader.
• Significant (as defined by the PI) intolerance of presently-used DMT, if taking a DMT
• The following must not have occurred during the original DISCO MS study or since completing the study:
• Use of any non-FDA-approved DMT
• Use of alemtuzumab, mitoxantrone, cyclophosphamide, methotrexate, cyclosporine, rituximab, or cladribine.
• Use of any experimental agent used as a DMT for MS
• Cancers other than basal cell skin cancers
• Other significant medical or psychiatric illness, if uncontrolled. Examples: uncontrolled hypertension, uncontrolled diabetes, uncontrolled asthma, uncontrolled depression.
• Unable to give informed consent or follow the protocol.
• Unable to undergo brain MRI.
• History of other chronic neurological illnesses that might mimic MS with chronic or intermittent symptoms (i.e. ALS, myasthenia gravis, chronic neuropathy, etc.).

Sponsors & Collaborators

• University of Colorado, Denver: lead
• EMD Serono: collaborator
• National Multiple Sclerosis Society: collaborator

Study Sites (10)

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

New York University

New York, New York, 10003, United States

Location

Mount Sinai

New York, New York, 10029, United States

Location

University of Rochester

Rochester, New York, 14627, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15260, United States

Location

Vanderbilt University

Nashville, Tennessee, 37235, United States

Location

University of Virginia

Charlottesville, Virginia, 22904, United States

Location

Swedish

Seattle, Washington, 98122, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Eric Engebretson
• Organization: University of Colorado Denver

eric.engebretson@cuanschutz.edu

3037244518

Study Officials

• John Corboy, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2021
• First Posted: February 15, 2021
• Study Start: May 18, 2021
• Primary Completion: November 30, 2022
• Study Completion: November 30, 2022
• Last Updated: September 25, 2024
• Results First Posted: September 25, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)