Clinical trial NCT03535298: Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for RRMS
Official title: Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for the Treatment of Relapsing-Remitting Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Multiple Sclerosis, Relapsing-Remitting
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: University of Nottingham
First posted: 2018-05-24
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Men and women aged 18 to 60 years.
2. Established diagnosis of MS, as defined by the 2017 revision of McDonald Diagnostic Criteria (99).
3. RRMS disease course as defined by the 2013 revisions of the MS clinical course definition (4).
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).
5. Participants must be ambulatory with disease onset ≤ 5 years and treatment-naïve (i.e., no MS DMT at any time in the past).
6. Participants must be eligible to receive at least one form of DMT within each treatment arm.
7. EDSS at Baseline visit ≤ 6.5

Exclusion Criteria:

1. Participants with contraindications to all forms of DMT in either of the treatment arms.
2. 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.
3. 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.
4. 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
5. Participants unable to provide informed consent.
6. 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.
7. 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.

Primary outcomes:
measure: Brain volume loss, baseline to month 36
timeFrame: Baseline to 36 months
measure: EDSS+, month 48 to month 72
timeFrame: 48 months to 72 months
Secondary outcomes:
measure: Brain volume loss, month 6 to month 36
timeFrame: Month 6 to month 36
measure: Proportion of participants with progression
timeFrame: Baseline to 36 months
measure: Change in MSIS-29, baseline to 36 months
timeFrame: Baseline to 36 months
measure: Change in Neuro-QOL, baseline to 36 months
timeFrame: Baseline to 36 months
measure: Time to reach SPMS, month 48 to month 72
timeFrame: 48 months to 72 months
measure: Efficacy difference between EHT and ESC, month 48 to month 72
timeFrame: 48 months to 72 months
measure: Safety difference between EHT and ESC, month 48 to month 72
timeFrame: 48 months to 72 months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado-Anschutz Medical Campus
state: Colorado
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Las Vegas
country: United States
facility: Cleveland Clinic Lou Ruvo Center for Brain Health
state: Nevada
city: Buffalo
country: United States
facility: University of Buffalo
state: New York
city: Rochester
country: United States
facility: University Rochester Medical Center
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio Health
state: Ohio
city: Austin
country: United States
facility: UT-Austin
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine, Houston
state: Texas
city: Houston
country: United States
facility: UTHealth-Houston
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin-Madison
state: Wisconsin
city: Coventry
country: United Kingdom
facility: University Hospitals Coventry and Warwickshire
state: England
city: Leeds
country: United Kingdom
facility: The Leeds Teaching Hospitals NHS Trust, Leeds General Infirmary
state: England
city: Leicester
country: United Kingdom
facility: University Hospitals Leicester
state: England
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust, Charing Cross Hospital
state: England
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust, University College Hospital
state: England
city: Manchester
country: United Kingdom
facility: Salford Royal NHS Foundation Trust, Salford Hospital
state: England
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital
state: England
city: Plymouth
country: United Kingdom
facility: University Hospitals Plymouth NHS Trust, Derriford Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals
state: England
city: Stoke
country: United Kingdom
facility: University Hospitals of North Midlands
state: England
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
state: Scotland
city: Cardiff
country: United Kingdom
facility: Cardiff and Vale University Local Health Board, University Hospital of Wales
state: Wales
city: Newport
country: United Kingdom
facility: Aneurin Bevan Local Health Board Headquarters, Royal Gwent Hospital
state: Wales
city: Swansea
country: United Kingdom
facility: Swansea Bay University Local Health Board, Morriston Hospital
state: Wales
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust, Queens Medical Centre
Study officials:
affiliation: The Cleveland Clinic
name: Daniel Ontaneda, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Nottingham
name: Nikos Evangelou, MD, DPhil
role: PRINCIPAL_INVESTIGATOR
References: