Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for the Treatment of Relapsing-Remitting Multiple Sclerosis
Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for RRMS
Sponsors
Source
The Cleveland Clinic
Oversight Info
Has Dmc
No
Is Fda Regulated Drug
Yes
Is Fda Regulated Device
No
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.
Overall Status
Recruiting
Start Date
2019-01-03
Completion Date
2023-09-01
Primary Completion Date
2022-12-31
Phase
Phase 4
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
|
Brain volume loss, baseline to month 36 |
Baseline to 36 months |
Secondary Outcome
Measure |
Time Frame |
|
Brain volume loss, month 6 to month 36 |
Month 6 to month 36 |
|
Proportion of participants with progression |
Baseline to 36 months |
|
Change in MSIS-29, baseline to 36 months |
Baseline to 36 months |
|
Change in Neuro-QOL, baseline to 36 months |
Baseline to 36 months |
Enrollment
800
Condition
Intervention
Intervention Type
Drug
Intervention Name
Description
Highly Effective MS Therapy group of medications
Arm Group Label
EHT: Early Highly-effective
Other Name
Lemtrada (alemtuzumab)
Ocrevus (ocrelizumab)
Tysabri (natalizumab)
Rituxan (rituximab)
Intervention Type
Drug
Intervention Name
Description
Escalation MS Therapy group of medications
Arm Group Label
ESC: Escalation
Other Name
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)
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, 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.
Gender
All
Minimum Age
18 Years
Maximum Age
60 Years
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
|
Daniel Ontaneda, MD, MSc |
Principal Investigator |
The Cleveland Clinic |
|
Nikos Evangelou, MD, DPhil |
Principal Investigator |
University of Nottingham |
Overall Contact
Location
Facility |
Status |
Contact |
Investigator |
|
University of Colorado-Anschutz Medical Campus Aurora Colorado 80045 United States |
Recruiting |
Last Name: Enrique. Alvarez,, MD,PhD Role: Principal Investigator | |
|
University of Minnesota Minneapolis Minnesota 55455 United States |
Not yet recruiting |
Last Name: William Schmalsteig, MD Role: Principal Investigator | |
|
Cleveland Clinic Lou Ruvo Center for Brain Health Las Vegas Nevada 89106 United States |
Recruiting |
Last Name: Carrie Hersh, DO, MSc Role: Principal Investigator | |
|
University of Buffalo Buffalo New York 14202 United States |
Not yet recruiting |
Last Name: Bianca Weinstock-Guttman, MD Role: Principal Investigator | |
|
University Rochester Medical Center Rochester New York 14642 United States |
Recruiting |
Last Name: Megan Hyland, MD Role: Principal Investigator | |
|
University of Cincinnati Cincinnati Ohio 45267 United States |
Recruiting |
Last Name: Aram Zabeti, MD Role: Principal Investigator | |
|
Cleveland Clinic Cleveland Ohio 44195 United States |
Recruiting |
Last Name: Daniel Ontaneda, MD, MSc Role: Principal Investigator | |
|
Ohio Health Columbus Ohio 43214 United States |
Recruiting |
Last Name: Jacqueline A Nicholas, MD, MPH Role: Principal Investigator | |
|
Baylor College of Medicine, Houston Houston Texas 77030 United States |
Recruiting |
Last Name: George Hutton, MD Role: Principal Investigator | |
|
UTHealth-Houston Houston Texas 77030 United States |
Recruiting |
Last Name: Rohini Samudralwar, MD Role: Principal Investigator | |
|
University of Virginia Charlottesville Virginia 22903 United States |
Recruiting |
Last Name: Myla Goldman, MD Role: Principal Investigator | |
|
University of Wisconsin-Madison Madison Wisconsin 53705 United States |
Recruiting |
Last Name: Natasha Frost, MD Role: Principal Investigator | |
|
Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital Cambridge England CB2 0AH United Kingdom |
Not yet recruiting |
Last Name: Alasdair Coles, MD Role: Principal Investigator | |
|
The Leeds Teaching Hospitals NHS Trust, Leeds General Infirmary Leeds England LS1 3EX United Kingdom |
Recruiting |
Last Name: Oliver Lily, MD Role: Principal Investigator | |
|
Imperial College Healthcare NHS Trust, Charing Cross Hospital London England W6 8RF United Kingdom |
Not yet recruiting |
Last Name: Richard Nicholas, MD Role: Principal Investigator | |
|
University College London Hospitals NHS Foundation Trust, University College Hospital London England WC1N 3BG United Kingdom |
Recruiting |
Last Name: Jeremy Chataway, MD Role: Principal Investigator | |
|
Salford Royal NHS Foundation Trust, Salford Hospital Manchester England M6 8HD United Kingdom |
Recruiting |
Last Name: Tatiana Mihalova, MD Role: Principal Investigator | |
|
Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital Oxford England OX3 9DU United Kingdom |
Not yet recruiting |
Last Name: Matthew Craner, MD Role: Principal Investigator | |
|
University Hospitals Plymouth NHS Trust, Derriford Hospital Plymouth England PL6 8DH United Kingdom |
Recruiting |
Last Name: Jeremy Hobart, MD Role: Principal Investigator | |
|
Cardiff and Vale University Local Health Board, University Hospital of Wales Cardiff Wales CF14 4XW United Kingdom |
Recruiting |
Last Name: Emma Tallantyre, MD Role: Principal Investigator | |
|
Aneurin Bevan Local Health Board Headquarters, Royal Gwent Hospital Newport Wales NP19 0BH United Kingdom |
Recruiting |
Last Name: Fady Joseph, ND Role: Principal Investigator | |
|
Swansea Bay University Local Health Board, Morriston Hospital Swansea Wales SA6 6NL United Kingdom |
Not yet recruiting |
Last Name: Owen Pearson, MD Role: Principal Investigator | |
|
Nottingham University Hospitals NHS Trust, Queens Medical Centre Nottingham NG7 2UH United Kingdom |
Recruiting |
Last Name: Nikos Evangelou, MD, DPhil Role: Principal Investigator |
Location Countries
Country
United Kingdom
United States
Verification Date
2019-08-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Principal Investigator
Investigator Affiliation
The Cleveland Clinic
Investigator Full Name
Daniel Ontaneda, MD
Investigator Title
Principal Investigator
Has Expanded Access
No
Condition Browse
Number Of Arms
3
Intervention Browse
Mesh Term
Interferons
Interferon-beta
Rituximab
Alemtuzumab
Glatiramer Acetate
Dimethyl Fumarate
Natalizumab
(T,G)-A-L
Arm Group
Arm Group Label
EHT: Early Highly-effective
Arm Group Type
Experimental
Description
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.
Arm Group Label
ESC: Escalation
Arm Group Type
Experimental
Description
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.
Arm Group Label
OBS: Observational
Arm Group Type
No Intervention
Description
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.
Firstreceived Results Date
N/A
Acronym
DELIVER-MS
Patient Data
Sharing Ipd
No
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)
Study First Submitted
May 14, 2018
Study First Submitted Qc
May 14, 2018
Study First Posted
May 24, 2018
Last Update Submitted
August 8, 2019
Last Update Submitted Qc
August 8, 2019
Last Update Posted
August 9, 2019
ClinicalTrials.gov processed this data on January 23, 2020
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.