Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for RRMS

• Register: ClinicalTrials.gov
• Last refreshed on: 6 May 2024
• Main ID: NCT03535298
• Date of registration: 14/05/2018
• Prospective Registration: Yes
• Primary sponsor: The Cleveland Clinic
• Public title: Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for RRMS DELIVER-MS
• Scientific title: Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for the Treatment of Relapsing-Remitting Multiple Sclerosis
• Date of first enrolment: January 3, 2019
• Target sample size: 800
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03535298
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

United Kingdom, United States

Contacts

• Name: Nikos Evangelou, MD, DPhil
• Affiliation: University of Nottingham

• Name: Daniel Ontaneda, MD, MSc
• Affiliation: The Cleveland Clinic

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 60 Years
Gender: All

Health Condition(s) or Problem(s) studied

Multiple Sclerosis, Relapsing-Remitting

Intervention(s)

Drug: Early Highly Effective Therapies Group

Drug: Escalation Therapies Group

Primary Outcome(s)

EDSS+, month 48 to month 72 [Time Frame: 48 months to 72 months]

Brain volume loss, baseline to month 36 [Time Frame: Baseline to 36 months]

Secondary Outcome(s)

Time to reach SPMS, month 48 to month 72 [Time Frame: 48 months to 72 months]

Brain volume loss, month 6 to month 36 [Time Frame: Month 6 to month 36]

Proportion of participants with progression [Time Frame: Baseline to 36 months]

Change in Neuro-QOL, baseline to 36 months [Time Frame: Baseline to 36 months]

Efficacy difference between EHT and ESC, month 48 to month 72 [Time Frame: 48 months to 72 months]

Change in MSIS-29, baseline to 36 months [Time Frame: Baseline to 36 months]

Safety difference between EHT and ESC, month 48 to month 72 [Time Frame: 48 months to 72 months]

Secondary ID(s)

CCF 18-326

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

University of Nottingham