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

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ClinicalTrials.gov Identifier: NCT03535298
Recruitment Status : Recruiting
First Posted : May 24, 2018
Last Update Posted : January 31, 2019
Sponsor:
Collaborator:
University of Nottingham
Information provided by (Responsible Party):
Daniel Ontaneda, MD, 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.

Condition or disease Intervention/treatment Phase
Multiple Sclerosis, Relapsing-Remitting Drug: Early Highly Effective Therapies Group Drug: Escalation Therapies Group Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : January 3, 2019
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine


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) 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)

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)

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.




Primary Outcome Measures :
  1. Brain volume loss, baseline to month 36 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline to 36 months ]
    Change in MSIS-29 responses from participants

  4. Change in Neuro-QOL, baseline to 36 months [ Time Frame: 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




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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, cladribine, interferon beta-1a, interferon beta-1b, pegylated interferon beta-1a, glatiramer acetate, fingolimod, teriflunomide, dimethyl fumarate, daclizumab, mitoxantrone.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03535298


Contacts
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Contact: Sarah Planchon Pope, PhD 216-636-1232 planchs@ccf.org

Locations
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United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Tammy Skaramagas, BA    216-445-6724    skaramt1@ccf.org   
Principal Investigator: Daniel Ontaneda, MD, MSc         
United Kingdom
University of Nottingham Not yet recruiting
Nottingham, United Kingdom, NG7 2UH
Contact: Sara Wilkins    +44 115 9249924 ext 66816    Sara.wilkins@nuh.nhs.uk   
Principal Investigator: Nikos Evangelou, MD, DPhil         
Sponsors and Collaborators
The Cleveland Clinic
University of Nottingham
Investigators
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Principal Investigator: Daniel Ontaneda, MD, MSc The Cleveland Clinic
Principal Investigator: Nikos Evangelou, MD, DPhil University of Nottingham

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Responsible Party: Daniel Ontaneda, MD, Principal Investigator, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT03535298     History of Changes
Other Study ID Numbers: CCF 18-326
First Posted: May 24, 2018    Key Record Dates
Last Update Posted: January 31, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Sclerosis
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Rituximab
Alemtuzumab
Glatiramer Acetate
(T,G)-A-L
Dimethyl Fumarate
Natalizumab
Interferon-beta
Interferons
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antiviral Agents
Anti-Infective Agents
Adjuvants, Immunologic
Immunosuppressive Agents
Dermatologic Agents