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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03535298
Other study ID # CCF 18-326
Secondary ID
Status Active, not recruiting
Phase Phase 4
First received
Last updated
Start date January 3, 2019
Est. completion date September 2030

Study information

Verified date April 2024
Source The Cleveland Clinic
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 800
Est. completion date September 2030
Est. primary completion date April 30, 2030
Accepts healthy volunteers No
Gender All
Age group 18 Years to 60 Years
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Early Highly Effective Therapies Group
Highly Effective MS Therapy group of medications
Escalation Therapies Group
Escalation MS Therapy group of medications

Locations

Country Name City State
United Kingdom Cardiff and Vale University Local Health Board, University Hospital of Wales Cardiff Wales
United Kingdom University Hospitals Coventry and Warwickshire Coventry England
United Kingdom Royal Infirmary of Edinburgh Edinburgh Scotland
United Kingdom The Leeds Teaching Hospitals NHS Trust, Leeds General Infirmary Leeds England
United Kingdom University Hospitals Leicester Leicester England
United Kingdom Imperial College Healthcare NHS Trust, Charing Cross Hospital London England
United Kingdom University College London Hospitals NHS Foundation Trust, University College Hospital London England
United Kingdom Salford Royal NHS Foundation Trust, Salford Hospital Manchester 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 Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital Oxford England
United Kingdom University Hospitals Plymouth NHS Trust, Derriford Hospital Plymouth England
United Kingdom Sheffield Teaching Hospitals Sheffield England
United Kingdom University Hospitals of North Midlands Stoke England
United Kingdom Swansea Bay University Local Health Board, Morriston Hospital Swansea Wales
United States University of Colorado-Anschutz Medical Campus Aurora Colorado
United States UT-Austin Austin Texas
United States University of Buffalo Buffalo New York
United States University of Virginia Charlottesville Virginia
United States University of Cincinnati Cincinnati Ohio
United States Cleveland Clinic Cleveland Ohio
United States Ohio Health Columbus Ohio
United States Baylor College of Medicine, Houston Houston Texas
United States UTHealth-Houston Houston Texas
United States Cleveland Clinic Lou Ruvo Center for Brain Health Las Vegas Nevada
United States University of Wisconsin-Madison Madison Wisconsin
United States University of Minnesota Minneapolis Minnesota
United States Virginia Commonwealth University Richmond Virginia
United States Mayo Clinic Rochester Minnesota
United States University Rochester Medical Center Rochester New York

Sponsors (2)

Lead Sponsor Collaborator
The Cleveland Clinic University of Nottingham

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Brain volume loss, baseline 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 Baseline to Month 36. Baseline to 36 months
Primary EDSS+, month 48 to month 72 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. 48 months to 72 months
Secondary Brain volume loss, 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. Month 6 to month 36
Secondary Proportion of participants with progression 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. Baseline to 36 months
Secondary Change in MSIS-29, baseline to 36 months Change in MSIS-29 responses from participants Baseline to 36 months
Secondary Change in Neuro-QOL, 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 Functioning
Baseline to 36 months
Secondary Time to reach SPMS, month 48 to month 72 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.
48 months to 72 months
Secondary Efficacy difference between EHT and ESC, month 48 to month 72 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.
48 months to 72 months
Secondary Safety difference between EHT and ESC, month 48 to month 72 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
48 months to 72 months
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