A Pragmatic Trial to Evaluate the Intermediate-term Effects of Early, Aggressive Versus Escalation Therapy in People With Multiple Sclerosis

Sponsor:

Brief Summary:

FDA-approved multiple sclerosis (MS) disease-modifying therapies (DMTs) target the relapsing
phase of MS but have minimal impact once the progressive phase has begun. It is unclear if,
in the relapsing phase, there is an advantage of early aggressive therapy with respect to
preventing long-term disability. The infectious risks and other complications associated with
higher-efficacy treatments highlight the need to quantify their effectiveness in preventing
disability.

The TRaditional versus Early Aggressive Therapy for MS (TREAT-MS) trial is a pragmatic,
randomized controlled trial that has two primary aims: 1) to evaluate, jointly and
independently among patients deemed at higher risk vs. lower risk for disability
accumulation, whether an “early aggressive” therapy approach, versus starting with a
traditional, first-line therapy, influences the intermediate-term risk of disability, and 2)
to evaluate if, among patients deemed at lower risk for disability who start on first-line MS
therapies but experience breakthrough disease, those who switch to a higher-efficacy versus a
new first-line therapy have different intermediate-term risk of disability.

Criteria

Inclusion Criteria:

– Aged 18-60 years

– Meets 2017 McDonald criteria for relapsing-remitting MS [patients with clinically
isolated syndrome (CIS) are not eligible]

– Must be EITHER John Cunningham (JC) virus antibody negative or low positive (index
antibody titer <0.9), OR negative for: Hepatitis B and C, tuberculosis - HIV negative - No chemotherapy in past year; if patient has prior history of chemotherapy or malignancy, documentation in chart explaining why potential risks of higher-efficacy therapy are justified Exclusion Criteria: - Prior treatment with rituximab, ocrelizumab, alemtuzumab, mitoxantrone or cladribine - Prior treatment with any other MS DMT for more than 6 months - Prior treatment with experimental aggressive therapies (e.g., T-cell vaccine, total lymphoid radiation, stem cells) - Treatment with teriflunomide within past 2 years (even for ≤ 6 months), unless rapid wash out done (i.e., with cholestyramine or activated charcoal) - Treatment in the past 6 months with any MS DMT - Prior treatment with any other investigational immune-modulating /suppressing drug for MS not listed above - Pregnant or breast-feeding - Women of child-bearing age who are planning or strongly considering conception during the study time frame

Locations

Dignity Health Medical Foundation, Carmichael, California, United States, 95608
Cedars-Sinai Medical Center, Los Angeles, California, United States, 90048
University of California, Los Angeles, Los Angeles, California, United States, 90095
University of California, San Diego, San Diego, California, United States, 92037
University of California, San Francisco, San Francisco, California, United States, 94158