Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for RRMS
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Interventions
- Drug: Early Highly Effective Therapies GroupDrug: Escalation Therapies Group
- Registration Number
- NCT03535298
- Lead Sponsor
- The Cleveland Clinic
- Brief Summary
The DELIVER-MS study seeks to answer the question: Does early treatment with highly effective DMT improve the prognosis for people with MS? This is an area of significant controversy and no data currently exist to guide treatment choices for patients and clinicians. The study results will help guide overall treatment philosophy and will be applicable not only to a wide range of existing therapies but also to new therapies, meeting a significant unmet need in patient decision making and aiding the decision for medication approval by third parties.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 800
- Men and women aged 18 to 60 years.
- Established diagnosis of MS, as defined by the 2017 revision of McDonald Diagnostic Criteria (99).
- RRMS disease course as defined by the 2013 revisions of the MS clinical course definition (4).
- Participants must have evidence of active disease based on: one or more MS relapses within the last 18 months prior to screening visit or radiological evidence of MS activity (≥2 new T2 lesions within the last 12 months from screening [compared to a previous recent MRI within 18 months of screening] or ≥1 GdE demonstrated on brain or spinal cord MRI performed within the last 12 months of screening).
- Participants must be ambulatory with disease onset ≤ 5 years and treatment-naïve (i.e., no MS DMT at any time in the past).
- Participants must be eligible to receive at least one form of DMT within each treatment arm.
- EDSS at Baseline visit ≤ 6.5
- Participants with contraindications to all forms of DMT in either of the treatment arms.
- Participants must never have received any of the following medications: natalizumab, alemtuzumab, ocrelizumab, rituximab, ofatumumab, cladribine, siponimod, interferon beta-1a, interferon beta-1b, pegylated interferon beta-1a, glatiramer acetate, fingolimod, teriflunomide, dimethyl fumarate, daclizumab, mitoxantrone, diroximel fumarate, ozanimod, monomethyl fumarate, ponesimod.
- Participants must have not received any of the following medications, for reasons other than MS, in the last 12 months: cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, leflunomide, laquinimod, atacicept, other monoclonal antibodies.
- Participants with clinically relevant medical or surgical conditions that, in the opinion of the investigator, would put the subject at risk by participating in the study
- Participants unable to provide informed consent.
- Contraindication or inability to undergo MRI with Gd due to metal or metal implants, allergy to Gd contrast, claustrophobia, pain, spasticity, or excessive movement related to tremor.
- Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that, in the opinion of the PI, is likely to affect the participant's ability to comply with the study protocol.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description EHT: Early Highly-effective Early Highly Effective Therapies Group Participants randomized to the "EHT: Early Highly-effective" arm will receive one of the highly effective MS therapies (Ocrevus, Lemtrada, Tysabri, Rituximab, Kesimpta) as their initial disease modifying treatment. Interventions: one of the highly effective MS therapies The randomization affects only the INITIAL treatment received. Once that treatment has been initiated, any subsequent changes are made according to standard clinical practice, regardless of randomization group. ESC: Escalation Escalation Therapies Group Participants randomized to the "ESC: Escalation" arm will receive any other approved MS therapy (not one of the EHT group) as their initial disease modifying treatment. Interventions: one of the MS therapies NOT in the highly effective group The randomization affects only the INITIAL treatment received. Once that treatment has been initiated, any subsequent changes are made according to standard clinical practice, regardless of randomization group.
- Primary Outcome Measures
Name Time Method Brain volume loss, baseline to month 36 Baseline to 36 months To determine whether an EHT approach to DMT, defined as use of one of four monoclonal antibodies (alemtuzumab, natalizumab, rituximab, or ocrelizumab) as first-line therapy, is more effective than an escalation of treatment approach in reducing normalized whole brain volume loss measured using MRI in PwRRMS from Baseline to Month 36.
EDSS+, month 48 to month 72 48 months to 72 months To determine whether an EHT approach to DMT, defined as use of one of six monoclonal antibodies (alemtuzumab, natalizumab, rituximab, ocrelizumab, ofatumumab, ublituximab) as first-line therapy, is more effective than an escalation of treatment approach in reducing time to reach a multidimensional composite comprised of EDSS+ worsening. EDSS+ worsening will be defined as worsening on ⩾ 1 of the 3 components: EDSS, 9HPT, or T25FW, which is confirmed at another visit after 12 months. EDSS worsening will be defined as a ⩾1.0-point increase from a baseline score of ⩽5.5 or a ⩾0.5-point increase from a baseline score of ⩾6.0. T25FW and 9HPT worsening will be defined as ⩾20% worsening from baseline.
- Secondary Outcome Measures
Name Time Method Efficacy difference between EHT and ESC, month 48 to month 72 48 months to 72 months To determine the efficacy of an EHT approach as compared to an escalation approach as reflected in the following patient-reported outcomes:
* The change in participant-perceived symptoms as measured by the MSIS-29.
* The change in participant quality of life as measured by Neuro-QOL.Change in Neuro-QOL, baseline to 36 months Baseline to 36 months 11 subscales, each is scored separately, there is no composite score
Physical Domains:
Upper Extremity Function (Fine Motor, ADL):
Higher scores indicate: Better Functioning
Lower Extremity Function (Mobility):
Higher scores indicate: Better Functioning
Fatigue:
Higher scores indicate: Worse Functioning
Sleep Disturbance:
Higher scores indicate: Worse Functioning
Mental Domains:
Cognition Function:
Higher scores indicate: Better Functioning
Stigma:
Higher scores indicate: Worse Functioning
Anxiety:
Higher scores indicate: Worse Functioning
Depression:
Higher scores indicate: Worse Functioning
Positive Affect and Well -being:
Higher scores indicate: Better Functioning
Social Domains:
Ability to Participate in Social Roles and Activities:
Higher scores indicate: Better Functioning
Satisfaction with Social Roles and Activities:
Higher scores indicate: Better FunctioningBrain volume loss, month 6 to month 36 Month 6 to month 36 To determine whether an EHT approach to DMT, defined as use of one of four monoclonal antibodies (alemtuzumab, natalizumab, rituximab, or ocrelizumab) as first-line therapy, is more effective than an escalation of treatment approach in reducing normalized whole brain volume loss measured using MRI in PwRRMS from Month 6 to Month 36.
Proportion of participants with progression Baseline to 36 months Proportion of participants with a multidimensional composite comprised of EDSS progression (\>1.5 points for those with EDSS of 0 at Baseline, ≥1.0 for those with EDSS of 0.5-5.0 at Baseline, and \>0.5 points for those with EDSS above 5.0 at Baseline), 20% change in MSFC-4 subcomponents (T25FW, 9HPT), 10% in SDMT or, 1 line change in LCLA confirmed over 12 months.
Time to reach SPMS, month 48 to month 72 48 months to 72 months To determine the efficacy of an EHT approach as compared to an escalation approach as reflected by the following:
* Time to reach secondary progressive MS (SPMS) as defined by worsening on the EDSS (3 strata definition for EDSS worsening plus EDSS score of ≥4 and pyramidal score ≥2), confirmed at 12 months, over 72 months
* Proportion of participants with a 20% or greater change in T25FW at 72 months.
* Proportion of participants with a 20% or greater change in 9HPT at 72 months.
* Proportion of participants with a 20% or greater change in the SDMT at 72 months.Change in MSIS-29, baseline to 36 months Baseline to 36 months Change in MSIS-29 responses from participants
Safety difference between EHT and ESC, month 48 to month 72 48 months to 72 months To determine the safety of an EHT approach as compared to an escalation approach as reflected in the following:
* Proportion of participants with SAEs
* Rate of SAEs
* Proportion of participants with DMT discontinuation due to safety or tolerability concerns
* Cumulative on-therapy TSQM Response scores
Trial Locations
- Locations (30)
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
University of Buffalo
🇺🇸Buffalo, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
University Rochester Medical Center
🇺🇸Rochester, New York, United States
Ohio Health
🇺🇸Columbus, Ohio, United States
Baylor College of Medicine, Houston
🇺🇸Houston, Texas, United States
UTHealth-Houston
🇺🇸Houston, Texas, United States
University Hospitals Coventry and Warwickshire
🇬🇧Coventry, England, United Kingdom
University Hospitals Leicester
🇬🇧Leicester, England, United Kingdom
Imperial College Healthcare NHS Trust, Charing Cross Hospital
🇬🇧London, England, United Kingdom
Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital
🇬🇧Oxford, England, United Kingdom
University College London Hospitals NHS Foundation Trust, University College Hospital
🇬🇧London, England, United Kingdom
University Hospitals of North Midlands
🇬🇧Stoke, England, United Kingdom
Aneurin Bevan Local Health Board Headquarters, Royal Gwent Hospital
🇬🇧Newport, Wales, United Kingdom
Nottingham University Hospitals NHS Trust, Queens Medical Centre
🇬🇧Nottingham, United Kingdom
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
UT-Austin
🇺🇸Austin, Texas, United States
Cleveland Clinic Lou Ruvo Center for Brain Health
🇺🇸Las Vegas, Nevada, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Salford Royal NHS Foundation Trust, Salford Hospital
🇬🇧Manchester, England, United Kingdom
The Leeds Teaching Hospitals NHS Trust, Leeds General Infirmary
🇬🇧Leeds, England, United Kingdom
University of Wisconsin-Madison
🇺🇸Madison, Wisconsin, United States
Royal Infirmary of Edinburgh
🇬🇧Edinburgh, Scotland, United Kingdom
Sheffield Teaching Hospitals
🇬🇧Sheffield, England, United Kingdom
Cardiff and Vale University Local Health Board, University Hospital of Wales
🇬🇧Cardiff, Wales, United Kingdom
Swansea Bay University Local Health Board, Morriston Hospital
🇬🇧Swansea, Wales, United Kingdom
University Hospitals Plymouth NHS Trust, Derriford Hospital
🇬🇧Plymouth, England, United Kingdom
University of Colorado-Anschutz Medical Campus
🇺🇸Aurora, Colorado, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States