Clincosm LogoSign in Get a demo

DELIVER-MS: Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for RRMS

Sponsor
The Cleveland Clinic (Other)
Overall Status
Recruiting
CT.gov ID
NCT03535298
Collaborator
University of Nottingham (Other)
800
Enrollment
31
Locations
3
Arms
91.9
Anticipated Duration (Months)
25.8
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Early Highly Effective Therapies Group
  • Drug: Escalation Therapies Group
 Phase 4

Study Design

Study Type:
Interventional
Anticipated Enrollment :
800 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for the Treatment of Relapsing-Remitting Multiple Sclerosis
Actual Study Start Date :
Jan 3, 2019
Anticipated Primary Completion Date :
Dec 31, 2025
Anticipated Study Completion Date :
Sep 1, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: EHT: Early Highly-effective

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.

Drug: Early Highly Effective Therapies Group
Highly Effective MS Therapy group of medications
Other Names:
  • Lemtrada (alemtuzumab)
  • Ocrevus (ocrelizumab)
  • Tysabri (natalizumab)
  • Rituxan (rituximab)
  • Kesimpta (ofatumumab)

    		•
    Experimental: ESC: Escalation

    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.

    Drug: Escalation Therapies Group
    Escalation MS Therapy group of medications
    Other Names:
  • Betaseron (beta interferon)
  • Copaxone (glatiramer acetate)
  • Aubagio (teriflunomide)
  • Extavia (beta interferon)
  • Gilenya (fingolimod)
  • Glatopa (glatiramer acetate)
  • Plegridy (beta interferon)
  • Rebif (beta interferon)
  • Tecfidera (dimethyl fumarate)
  • Avonex (beta interferon)
  • Mavenclad (cladribine)
  • Mayzent (siponimod)
  • Vumerity (diroximel fumarate)
  • Zeposia (ozanimod)
  • Bafiertam (monomethyl fumarate)
  • Ponvory (ponesimod)

    		•
    No Intervention: OBS: Observational

    Participants will not be restricted to a group of MS therapies. Participants enter this arm if they are not comfortable with randomization, are not eligible to receive any of the options in a randomized arm, or are not able to secure insurance coverage for any therapy in a randomized arm.

    Outcome Measures

    Primary Outcome Measures

    1. 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.

    Secondary Outcome Measures

    1. Brain 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.

    2. 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.

    3. Change in MSIS-29, baseline to 36 months [Baseline to 36 months]

      Change in MSIS-29 responses from participants

    4. 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 Functioning

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Colorado-Anschutz Medical Campus Aurora Colorado United States 80045
    2 University of Minnesota Minneapolis Minnesota United States 55455
    3 Mayo Clinic Rochester Minnesota United States 55902
    4 Cleveland Clinic Lou Ruvo Center for Brain Health Las Vegas Nevada United States 89106
    5 University of Buffalo Buffalo New York United States 14202
    6 University Rochester Medical Center Rochester New York United States 14642
    7 University of Cincinnati Cincinnati Ohio United States 45267
    8 Cleveland Clinic Cleveland Ohio United States 44195
    9 Ohio Health Columbus Ohio United States 43214
    10 UT-Austin Austin Texas United States 78712
    11 Baylor College of Medicine, Houston Houston Texas United States 77030
    12 UTHealth-Houston Houston Texas United States 77030
    13 University of Virginia Charlottesville Virginia United States 22903
    14 Virginia Commonwealth University Richmond Virginia United States 23284
    15 University of Wisconsin-Madison Madison Wisconsin United States 53705
    16 University Hospitals Coventry and Warwickshire Coventry England United Kingdom CV2 2DX
    17 Frimley Park Frimley England United Kingdom GU16 7UJ
    18 The Leeds Teaching Hospitals NHS Trust, Leeds General Infirmary Leeds England United Kingdom LS1 3EX
    19 University Hospitals Leicester Leicester England United Kingdom LE1 5WW
    20 Imperial College Healthcare NHS Trust, Charing Cross Hospital London England United Kingdom W6 8RF
    21 University College London Hospitals NHS Foundation Trust, University College Hospital London England United Kingdom WC1N 3BG
    22 Salford Royal NHS Foundation Trust, Salford Hospital Manchester England United Kingdom M6 8HD
    23 Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital Oxford England United Kingdom OX3 9DU
    24 University Hospitals Plymouth NHS Trust, Derriford Hospital Plymouth England United Kingdom PL6 8DH
    25 Sheffield Teaching Hospitals Sheffield England United Kingdom S5 7AT
    26 University Hospitals of North Midlands Stoke England United Kingdom ST4 6QG
    27 Royal Infirmary of Edinburgh Edinburgh Scotland United Kingdom EH16 4SA
    28 Cardiff and Vale University Local Health Board, University Hospital of Wales Cardiff Wales United Kingdom CF14 4XW
    29 Aneurin Bevan Local Health Board Headquarters, Royal Gwent Hospital Newport Wales United Kingdom NP19 0BH
    30 Swansea Bay University Local Health Board, Morriston Hospital Swansea Wales United Kingdom SA6 6NL
    31 Nottingham University Hospitals NHS Trust, Queens Medical Centre Nottingham United Kingdom NG7 2UH

    Sponsors and Collaborators

    • The Cleveland Clinic
    • University of Nottingham

    Investigators

    • Principal Investigator: Daniel Ontaneda, MD, MSc, The Cleveland Clinic
    • Principal Investigator: Nikos Evangelou, MD, DPhil, University of Nottingham

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Daniel Ontaneda, MD, Principal Investigator, The Cleveland Clinic
    ClinicalTrials.gov Identifier:
    NCT03535298
    Other Study ID Numbers:
    • CCF 18-326
    First Posted:
    May 24, 2018
    Last Update Posted:
    Jul 25, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Multiple Sclerosis
    Multiple Sclerosis, Relapsing-Remitting
    Sclerosis
    Interferons
    Interferon-beta
    Teriflunomide
    Alemtuzumab
    Ofatumumab
    Cladribine
    Glatiramer Acetate
    Dimethyl Fumarate
    Ocrelizumab
    Fingolimod Hydrochloride
    Natalizumab
    (T,G)-A-L
    Ozanimod
    Ponesimod
    Siponimod

    Study Results

    No Results Posted as of Jul 25, 2022