Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for RRMS

Multiple Sclerosis, Relapsing-Remitting Clinical Trial

— DELIVER-MS  

Official title:

Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for the Treatment of Relapsing-Remitting Multiple Sclerosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03535298
• Other study ID #: CCF 18-326
• Status: Recruiting
• Phase: Phase 4
• Start date: January 3, 2019
• Est. completion date: September 2030

Study information

• Verified date: August 2023
• Source: The Cleveland Clinic
• Contact: Sarah Planchon Pope, PhD
• Phone: 216-636-1232
• Email: planchs[@]ccf.org
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 800
• Est. completion date: September 2030
• Est. primary completion date: April 30, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

Drug:
• Early Highly Effective Therapies Group
Highly Effective MS Therapy group of medications
• Escalation Therapies Group
Escalation MS Therapy group of medications

Locations

Country	Name	City	State
United Kingdom	Cardiff and Vale University Local Health Board, University Hospital of Wales	Cardiff	Wales
United Kingdom	University Hospitals Coventry and Warwickshire	Coventry	England
United Kingdom	Royal Infirmary of Edinburgh	Edinburgh	Scotland
United Kingdom	Frimley Park	Frimley	England
United Kingdom	The Leeds Teaching Hospitals NHS Trust, Leeds General Infirmary	Leeds	England
United Kingdom	University Hospitals Leicester	Leicester	England
United Kingdom	Imperial College Healthcare NHS Trust, Charing Cross Hospital	London	England
United Kingdom	University College London Hospitals NHS Foundation Trust, University College Hospital	London	England
United Kingdom	Salford Royal NHS Foundation Trust, Salford Hospital	Manchester	England
United Kingdom	Aneurin Bevan Local Health Board Headquarters, Royal Gwent Hospital	Newport	Wales
United Kingdom	Nottingham University Hospitals NHS Trust, Queens Medical Centre	Nottingham
United Kingdom	Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital	Oxford	England
United Kingdom	University Hospitals Plymouth NHS Trust, Derriford Hospital	Plymouth	England
United Kingdom	Sheffield Teaching Hospitals	Sheffield	England
United Kingdom	University Hospitals of North Midlands	Stoke	England
United Kingdom	Swansea Bay University Local Health Board, Morriston Hospital	Swansea	Wales
United States	University of Colorado-Anschutz Medical Campus	Aurora	Colorado
United States	UT-Austin	Austin	Texas
United States	University of Buffalo	Buffalo	New York
United States	University of Virginia	Charlottesville	Virginia
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Ohio Health	Columbus	Ohio
United States	Baylor College of Medicine, Houston	Houston	Texas
United States	UTHealth-Houston	Houston	Texas
United States	Cleveland Clinic Lou Ruvo Center for Brain Health	Las Vegas	Nevada
United States	University of Wisconsin-Madison	Madison	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	University Rochester Medical Center	Rochester	New York

Sponsors (2)

Lead Sponsor	Collaborator
The Cleveland Clinic	University of Nottingham

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline to 36 months
Primary	EDSS+, month 48 to month 72	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.	48 months to 72 months
Secondary	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.	Month 6 to month 36
Secondary	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.	Baseline to 36 months
Secondary	Change in MSIS-29, baseline to 36 months	Change in MSIS-29 responses from participants	Baseline to 36 months
Secondary	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	Baseline to 36 months
Secondary	Time to reach SPMS, month 48 to month 72	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 72 months; Proportion of participants with a 20% or greater change in T25FW at 72 months.; Proportion of participants with a 20% or greater change in 9HPT at 72 months.; Proportion of participants with a 20% or greater change in the SDMT at 72 months.	48 months to 72 months
Secondary	Efficacy difference between EHT and ESC, month 48 to month 72	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.	48 months to 72 months
Secondary	Safety difference between EHT and ESC, month 48 to month 72	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	48 months to 72 months