Intensive vs Escalation Therapy Approaches for Multiple Sclerosis

(DELIVER-MS Trial)

Recruiting at 30 trial locations

Overseen By Karina Vences

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: The Cleveland Clinic

Must not be taking: Monoclonal antibodies, Immunosuppressants

Disqualifiers: Contraindications to DMT, MRI issues, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 36 months

800 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires participants to be treatment-naïve, meaning they should not have taken any MS disease-modifying therapies (DMTs) in the past. Additionally, participants must not have taken certain other medications for reasons other than MS in the last 12 months.

What data supports the effectiveness of early highly effective therapies for multiple sclerosis?

Research suggests that starting treatment with highly effective drugs early in the course of multiple sclerosis can lead to better long-term outcomes compared to starting with less effective drugs and escalating if needed. This approach takes advantage of a 'window of opportunity' to maximize benefits and potentially prevent irreversible disability. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

The escalation approach starts with treatments that have fewer side effects, while the early intense therapy approach uses more effective treatments that may have more side effects. Both strategies are used in treating multiple sclerosis, but the safety of each depends on the specific drugs used. ^{1 2 4 6 7}

How does the early highly effective therapy for multiple sclerosis differ from other treatments?

The early highly effective therapy for multiple sclerosis involves starting treatment with powerful drugs right away to maximize long-term benefits, even though they may have more side effects. This is different from the traditional escalation approach, which starts with milder drugs and only moves to stronger ones if needed. ^{1 2 3 4 7}

Research Team

Nikos Evangelou, MD, DPhil

Principal Investigator

University of Nottingham

Daniel Ontaneda, MD, PhD

Principal Investigator

The Cleveland Clinic

Eligibility Criteria

This trial is for men and women aged 18 to 60 with Relapsing-Remitting Multiple Sclerosis (RRMS), diagnosed per the latest criteria, who have had active disease recently but haven't taken any MS drugs before. They should be able to walk and have had MS symptoms start within the last five years.

Inclusion Criteria

I am between 18 and 60 years old.

I can walk, was diagnosed with my condition less than 5 years ago, and have never taken disease-modifying treatments.

I am eligible for at least one type of disease-modifying treatment.

Exclusion Criteria

I cannot use any standard disease-modifying treatments due to health reasons.

I am unable to understand and give consent for treatment.

I haven't taken the specified medications for non-MS reasons in the past year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either early highly-effective MS therapies or escalation MS therapies as their initial disease modifying treatment

36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Long-term Follow-up

Participants are monitored for efficacy and safety differences between treatment approaches

24 months

Treatment Details

Interventions

• Early Highly Effective Therapies Group
• Escalation Therapies Group

Trial Overview The DELIVER-MS study compares two treatment strategies: one starts with strong Disease Modifying Therapies (DMTs) early on, while the other begins with less intense treatments and increases only if needed. The goal is to see which approach leads to better long-term outcomes.

Participant Groups

Group I: ESC: Escalation Experimental Treatment 1 Intervention

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.

Group II: EHT: Early Highly-effective Experimental Treatment 1 Intervention

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.

Group III: OBS: Observational Active Control 1 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 Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

University of Nottingham

Collaborator

Trials

540

Recruited

2,317,000+

Findings from Research

Starting treatment with ofatumumab (OMB) immediately or switching to it early after one year on other therapies leads to better clinical outcomes in relapsing multiple sclerosis, including fewer relapses and higher employment rates, compared to delaying treatment or not switching at all.

The cost analysis shows that while immediate OMB treatment has higher drug costs, these are nearly offset by reduced patient care costs and productivity losses, making it a cost-effective option in the long run.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing the long-term clinical and economic impact of ofatumumab versus dimethyl fumarate and glatiramer acetate in patients with relapsing multiple sclerosis: A cost-consequence analysis from a societal perspective in Germany. Koeditz, D., Frensch, J., Bierbaum, M., et al.[2023]

The current treatment strategies for multiple sclerosis (MS) are debated, with two main approaches: the escalation strategy, which starts with low-efficacy drugs and moves to higher-efficacy options if needed, and the early intense therapy strategy, which begins with high-efficacy drugs despite their potential side effects.

Evidence supporting the escalation strategy is primarily based on short-term studies and does not adequately address the disease's heterogeneity or the limited impact of relapses on long-term outcomes, leaving the effectiveness of both strategies still uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Escalation vs. Early Intense Therapy in Multiple Sclerosis. Casanova, B., Quintanilla-Bordás, C., Gascón, F.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Comparing the long-term clinical and economic impact of ofatumumab versus dimethyl fumarate and glatiramer acetate in patients with relapsing multiple sclerosis: A cost-consequence analysis from a societal perspective in Germany. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Escalation vs. Early Intense Therapy in Multiple Sclerosis. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Cost, efficacy, and safety comparison between early intensive and escalating strategies for multiple sclerosis: A systematic review and meta-analysis. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Highly Effective Therapy Versus Escalation Approaches in Early Multiple Sclerosis: What Is the Future of Multiple Sclerosis Treatment? [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Timing of high-efficacy therapy in relapsing-remitting multiple sclerosis: A systematic review. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Achieving no evidence of disease activity-3 in highly active multiple sclerosis patients treated with cladribine and monoclonal antibodies. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Early High-Efficacy Versus Escalation Therapy in Relapsing-Remitting Multiple Sclerosis in Argentina. [2022]