Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for RRMS (DELIVER-MS)
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| ClinicalTrials.gov Identifier: NCT03535298 |
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Recruitment Status :
Recruiting
First Posted : May 24, 2018
Last Update Posted : July 25, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Multiple Sclerosis, Relapsing-Remitting | Drug: Early Highly Effective Therapies Group Drug: Escalation Therapies Group | Phase 4 |
| 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, 2025 |
| Estimated Study Completion Date : | September 2026 |
| Arm | Intervention/treatment |
|---|---|
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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, 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
Highly Effective MS Therapy group of medications
Other Names:
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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:
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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. |
- 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.
- 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.
- 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.
- Change in MSIS-29, baseline to 36 months [ Time Frame: Baseline to 36 months ]Change in MSIS-29 responses from participants
- 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 60 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
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
| Contact: Sarah Planchon Pope, PhD | 216-636-1232 | planchs@ccf.org |
Show 31 study locations
| Principal Investigator: | Daniel Ontaneda, MD, MSc | The Cleveland Clinic | |
| Principal Investigator: | Nikos Evangelou, MD, DPhil | University of Nottingham |
| Responsible Party: | Daniel Ontaneda, MD, Principal Investigator, The Cleveland Clinic |
| ClinicalTrials.gov Identifier: | NCT03535298 |
| Other Study ID Numbers: |
CCF 18-326 |
| First Posted: | May 24, 2018 Key Record Dates |
| Last Update Posted: | July 25, 2022 |
| Last Verified: | July 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Multiple Sclerosis Multiple Sclerosis, Relapsing-Remitting Sclerosis Pathologic Processes Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System Nervous System Diseases Demyelinating Diseases Autoimmune Diseases Immune System Diseases Interferons Interferon-beta Teriflunomide Alemtuzumab Ofatumumab |
Cladribine Glatiramer Acetate Dimethyl Fumarate Ocrelizumab Natalizumab Fingolimod Hydrochloride (T,G)-A-L Ozanimod Ponesimod Siponimod Antineoplastic Agents, Immunological Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents |