Multiple Sclerosis, Relapsing-RemittingPhase 4DELIVER-MSNCT03535298
Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for RRMS
A Phase 4 study testing Early Highly Effective Therapies Group and Escalation Therapies Group in people with Multiple Sclerosis, Relapsing-Remitting, run by The Cleveland Clinic at 30 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting
- What is being tested?
- Early Highly Effective Therapies Group and Escalation Therapies Group
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 800 participants
- Where
- 30 sitesin 2 countries
- Study dates
- 3 Jan 2019to 30 Jul 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Men and women aged 18 to 60 years.
- Established diagnosis of MS, as defined by the 2017 revision of McDonald Diagnostic Criteria (99).
- RRMS disease course as defined by the 2013 revisions of the MS clinical course definition (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).
- Participants must be ambulatory with disease onset ≤ 5 years and treatment-naïve (i.e., no MS DMT at any time in the past).
- Participants must be eligible to receive at least one form of DMT within each treatment arm.
- EDSS at Baseline visit ≤ 6.5
Who cannot join
- Participants with contraindications to all forms of DMT in either of the treatment arms.
- 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.
- 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.
- 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
- Participants unable to provide informed consent.
- 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.
- 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.
Trial locations and contacts
30 sites in 2 countries.
30 sites in 2 countries
United States15 sites
University of Colorado-Anschutz Medical Campus
Aurora, Colorado, 80045
UT-Austin
Austin, Texas, 78712
University of Buffalo
Buffalo, New York, 14202
University of Virginia
Charlottesville, Virginia, 22903
University of Cincinnati
Cincinnati, Ohio, 45267
Cleveland Clinic
Cleveland, Ohio, 44195
Ohio Health
Columbus, Ohio, 43214
Baylor College of Medicine, Houston
Houston, Texas, 77030
UTHealth-Houston
Houston, Texas, 77030
Cleveland Clinic Lou Ruvo Center for Brain Health
Las Vegas, Nevada, 89106
University of Wisconsin-Madison
Madison, Wisconsin, 53705
University of Minnesota
Minneapolis, Minnesota, 55455
Virginia Commonwealth University
Richmond, Virginia, 23284
Mayo Clinic
Rochester, Minnesota, 55902
University Rochester Medical Center
Rochester, New York, 14642
United Kingdom15 sites
Cardiff and Vale University Local Health Board, University Hospital of Wales
Cardiff, Wales, CF14 4XW
University Hospitals Coventry and Warwickshire
Coventry, England, CV2 2DX
Royal Infirmary of Edinburgh
Edinburgh, Scotland, EH16 4SA
The Leeds Teaching Hospitals NHS Trust, Leeds General Infirmary
Leeds, England, LS1 3EX
University Hospitals Leicester
Leicester, England, LE1 5WW
Imperial College Healthcare NHS Trust, Charing Cross Hospital
London, England, W6 8RF
University College London Hospitals NHS Foundation Trust, University College Hospital
London, England, WC1N 3BG
Salford Royal NHS Foundation Trust, Salford Hospital
Manchester, England, M6 8HD
Aneurin Bevan Local Health Board Headquarters, Royal Gwent Hospital
Newport, Wales, NP19 0BH
Nottingham University Hospitals NHS Trust, Queens Medical Centre
Nottingham, NG7 2UH
Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital
Oxford, England, OX3 9DU
University Hospitals Plymouth NHS Trust, Derriford Hospital
Plymouth, England, PL6 8DH
Sheffield Teaching Hospitals
Sheffield, England, S5 7AT
University Hospitals of North Midlands
Stoke, England, ST4 6QG
Swansea Bay University Local Health Board, Morriston Hospital
Swansea, Wales, SA6 6NL
About this study
Official title: Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for the Treatment of Relapsing-Remitting Multiple Sclerosis
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.
Read the detailed description
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.
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Being tested
- Early Highly Effective Therapies Group, Escalation Therapies Group
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Early Highly Effective Therapies GroupDrug
Also called Lemtrada (alemtuzumab), Ocrevus (ocrelizumab), Tysabri (natalizumab), Rituxan (rituximab)
Highly Effective MS Therapy group of medications
Escalation Therapies GroupDrug
Also called Betaseron (beta interferon), Copaxone (glatiramer acetate), Aubagio (teriflunomide), Extavia (beta interferon)
Escalation MS Therapy group of medications
| Study group | Role | What they receive |
|---|---|---|
| EHT: Early Highly-effective | Experimental | 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. Receives: Drug: Early Highly Effective Therapies Group |
| ESC: Escalation | Experimental | 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. Receives: Drug: Escalation Therapies Group |
| OBS: Observational | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 48 months to 108 months
Secondary outcomes (7)
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.
Measured: 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.
Measured: Baseline to 36 months
Change in MSIS-29, baseline to 36 months
Change in MSIS-29 responses from participants
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
Measured: 48 months to 108 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2018
- Study start3 Jan 2019
- Primary completion30 Jul 2027 (estimated)
- Study completion30 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple Sclerosis, Relapsing-RemittingStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 800 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- University of Nottingham
- Responsible party
- Principal investigator, Daniel Ontaneda, MD, The Cleveland Clinic
- Investigators
- Daniel Ontaneda, MD, MSc, Principal investigator, The Cleveland ClinicNikos Evangelou, MD, DPhil, Principal investigator, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03535298
- Sponsor's protocol ID
- CCF 18-326/23-453
- Acronym
- DELIVER-MS
- Status last verified
- Aug 2026
- First submitted
- 14 May 2018
- Last updated
- 31 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tallantyre EC, Planchon SM, Howard H, Mays J, Frowd N, Cohen JA, Coles A, Hersh CM, Miller DM, Dever M, Gray EH, LaRocca NG, Nakamura K, Bale C, Covey-Crump G, Alvarez E, Arun T, Brownlee WJ, Craner M, Freeman L, Frost N, Goldman MD, Gupta RK, Harding KE, Hobart J, Hutton GJ, Hyland MH, Kalra S, Kannan M, Kantarci O, Lashley D, Lily O, Mahad D, Nicholas JA, Nicholas R, Paling D, Pearson OR, Rice CM, Samudralwar R, Schmalstieg WF, Singh M, Zune The E, Weinstock-Guttman B, Zabeti A, Love TE, Gunzler DD, Liu Y, Gerry S, Evangelou N, Ontaneda D. Disease-modifying treatment preferences and decision-making in a multiple sclerosis randomized and observational clinical trial (DELIVER-MS). Mult Scler. 2026 Jun;32(7):722-736. doi: 10.1177/13524585261449988. Epub 2026 May 31.
PubMed 42218617
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for the Treatment of Relapsing-Remitting Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT03535298
- Acronym / sponsor ID
- DELIVER-MS / CCF 18-326/23-453
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 800 participants (estimated)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Collaborators
- University of Nottingham
- Study start
- 3 Jan 2019 (actual)
- Primary completion
- 30 Jul 2027 (estimated)
- Study completion
- 30 Jul 2027 (estimated)
- First posted
- 24 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| EHT: Early Highly-effective | Experimental | Drug: Early Highly Effective Therapies GroupParticipants 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. |
| ESC: Escalation | Experimental | Drug: Escalation Therapies GroupParticipants 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. |
| OBS: Observational | No intervention | –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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Men and women aged 18 to 60 years.
- Established diagnosis of MS, as defined by the 2017 revision of McDonald Diagnostic Criteria (99).
- RRMS disease course as defined by the 2013 revisions of the MS clinical course definition (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).
- Participants must be ambulatory with disease onset ≤ 5 years and treatment-naïve (i.e., no MS DMT at any time in the past).
Key exclusion criteria (7 listed)
- Participants with contraindications to all forms of DMT in either of the treatment arms.
- 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.
- 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.
- 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
- Participants unable to provide informed consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Early Highly Effective Therapies GroupAlso: Lemtrada (alemtuzumab), Ocrevus (ocrelizumab), Tysabri (natalizumab), Rituxan (rituximab)Highly Effective MS Therapy group of medications | Drug | EHT: Early Highly-effective |
| Escalation Therapies GroupAlso: Betaseron (beta interferon), Copaxone (glatiramer acetate), Aubagio (teriflunomide), Extavia (beta interferon)Escalation MS Therapy group of medications | Drug | ESC: Escalation |
Primary outcome
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.
EDSS+, month 48 to month 108
Time frame: 48 months to 108 months
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.
7 secondary outcomes
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 MSIS-29, baseline to 36 months
Time frame: Baseline to 36 months
Change in Neuro-QOL, baseline to 36 months
Time frame: Baseline to 36 months
Time to reach SPMS, month 48 to month 108
Time frame: 48 months to 108 months
Efficacy difference between EHT and ESC, month 48 to month 108
Time frame: 48 months to 108 months
Safety difference between EHT and ESC, month 48 to month 108
Time frame: 48 months to 108 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2026.
- Derived from this study: PubMed 42218617Tallantyre EC, Planchon SM, Howard H, Mays J, Frowd N, Cohen JA, Coles A, Hersh CM, Miller DM, Dever M, Gray EH, LaRocca NG, Nakamura K, Bale C, Covey-Crump G, Alvarez E, Arun T, Brownlee WJ, Craner M, Freeman L, Frost N, Goldman MD, Gupta RK, Harding KE, Hobart J, Hutton GJ, Hyland MH, Kalra S, Kannan M, Kantarci O, Lashley D, Lily O, Mahad D, Nicholas JA, Nicholas R, Paling D, Pearson OR, Rice CM, Samudralwar R, Schmalstieg WF, Singh M, Zune The E, Weinstock-Guttman B, Zabeti A, Love TE, Gunzler DD, Liu Y, Gerry S, Evangelou N, Ontaneda D. Disease-modifying treatment preferences and decision-making in a multiple sclerosis randomized and observational clinical trial (DELIVER-MS). Mult Scler. 2026 Jun;32(7):722-736. doi: 10.1177/13524585261449988. Epub 2026 May 31.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel Ontaneda, MD, MSc principal investigator
The Cleveland Clinic
Nikos Evangelou, MD, DPhil principal investigator
University of Nottingham
30 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Early Highly Effective Therapies Group and Escalation Therapies Group in people with Multiple Sclerosis, Relapsing-Remitting, run by The Cleveland Clinic at 30 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brain volume loss, baseline to month 36 (time frame: Baseline to 36 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03535298, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2026.