A Phase 4 interventional study of Early Highly Effective Therapies Group and Escalation Therapies Group in Multiple Sclerosis, Relapsing-Remitting, sponsored by The Cleveland Clinic. Active, not recruiting at 30 sites in 2 countries. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2026-08-31.
Sponsored by The Cleveland Clinic · Phase 4, Interventional, and Treatment
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.
DELIVER-MS is a multi-center pragmatic comparative effectiveness randomized clinical trial with additional-parallel observational cohort. It aims to enroll up to 400 individuals newly diagnosed with RRMS and randomize them 1:1 to Early Highly Effective (EHT) or Escalation (ESC) treatment paradigms, based on the use of different disease modifying therapies (DMT) as first-line therapy. EHT approach to DMT is defined as use of one of five monoclonal antibodies (alemtuzumab, natalizumab, rituximab, ocrelizumab, ofatumumab, ublituximab) as first-line therapy. ESC approach is defined as initiating any other approved MS DMT as first-line therapy, then escalating to a more effective therapy upon disease activity. Once randomized, the Neurologist and Participant decide which DMT within the arm is most appropriate. After the initial DMT is initiated, if a DMT change is needed, the second-line therapy may be chosen from either arm, regardless of randomization. The randomization only applies to the initial DMT choice.
Up to 400 individuals who do are not amenable to randomization or who agree to randomization but are not approved for coverage for a medication in the arm to which they were randomized will enter the Observational Arm. In the Observational Arm, the DMT chosen is from any approved DMT for MS and is chosen by the Neurologist and participant.
All study procedures throughout are identical between the randomized and observation alarm, except for the randomization.
The primary objective for the initial 36 months of the study is normalized whole brain volume loss, measured using MRI from baseline to Month 36. The primary objective for the long term extension of the study (Months 48-108) is the EDSS+, a composite measure of clinical disability based on the EDSS and MSFC.
The study is performed primarily in tertiary MS Centers in the US and UK.
602 studies on the registry are indexed under Multiple Sclerosis, Relapsing-Remitting; 80 are open to participants now.
This study's planned enrollment of 800 is above the median of 72 across 429 interventional studies indexed under Multiple Sclerosis, Relapsing-Remitting.
Browse Multiple Sclerosis, Relapsing-Remitting studies →The Cleveland Clinic is the lead sponsor of 818 studies on the registry; 118 are open to participants now.
Of its 89 completed or terminated interventional studies of FDA-regulated products, 72 (81%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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
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
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.
Highly Effective MS Therapy group of medications
Also known as: Lemtrada (alemtuzumab), Ocrevus (ocrelizumab), Tysabri (natalizumab), Rituxan (rituximab), Kesimpta (ofatumumab), Briumvi (ublituximab)
Escalation MS Therapy group of medications
Also known as: 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)
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.
Time frame: Baseline to 36 months
EDSS+, month 48 to month 108
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.
Time frame: 48 months to 108 months
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.
Time frame: Month 6 to month 36
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.
Time frame: Baseline to 36 months
Change in MSIS-29, baseline to 36 months
Change in MSIS-29 responses from participants
Time frame: Baseline to 36 months
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
Time frame: Baseline to 36 months
Time to reach SPMS, month 48 to month 108
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 108 months * Proportion of participants with a 20% or greater change in T25FW at 108 months. * Proportion of participants with a 20% or greater change in 9HPT at 108 months. * Proportion of participants with a 20% or greater change in the SDMT at 108 months.
Time frame: 48 months to 108 months
Efficacy difference between EHT and ESC, month 48 to month 108
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.
Time frame: 48 months to 108 months
Safety difference between EHT and ESC, month 48 to month 108
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
Time frame: 48 months to 108 months
Plan to share: No
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Multiple Sclerosis, Relapsing-Remitting→
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