Intensive vs Escalation Therapy Approaches for Multiple Sclerosis

(DELIVER-MS Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if starting treatment early with highly effective disease-modifying therapies (DMT) improves the long-term outlook for people with multiple sclerosis (MS). Participants are divided into two groups: the Early Highly Effective Therapies Group receives early treatment with powerful MS drugs, while the Escalation Therapies Group starts with less aggressive therapies and escalates as needed. The trial seeks to provide answers that guide treatment choices for both new and existing therapies. Suitable candidates have been diagnosed with MS, experienced a relapse in the past 18 months, and have not yet started any MS treatment. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, aiming to understand how it benefits more patients.

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 is the safety track record for these treatments?

A previous study demonstrated that ocrelizumab, a very effective treatment, produced strong results and was well-tolerated by people with multiple sclerosis (MS). Other treatments in this group, such as natalizumab, also maintain a good safety record. Research has shown that starting treatment with these highly effective drugs can reduce the risk of new MRI lesions, which indicate MS activity in the brain.

Conversely, studies have shown that while escalation therapies are generally safe, they might not be as effective as the highly effective ones in preventing MS from worsening early on. However, they remain safe options for many patients.

Overall, both treatment groups are well-tolerated, but the highly effective therapies have demonstrated better results in controlling MS sooner. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the different therapy approaches for multiple sclerosis (MS) because they offer insights into treatment effectiveness right from the start. The Early Highly Effective Therapies (EHT) approach is unique because it uses potent MS drugs like Ocrevus, Lemtrada, and Tysabri as the initial treatment, potentially leading to better long-term outcomes by aggressively targeting the disease early on. On the other hand, the Escalation Therapy approach starts with standard MS treatments and gradually moves to stronger options if needed, allowing for a tailored treatment progression. Understanding which method provides better control over MS could significantly improve how the disease is managed from its onset, potentially enhancing quality of life for patients.

What evidence suggests that this trial's treatments could be effective for multiple sclerosis?

In this trial, participants will be randomized into different treatment arms to compare approaches for managing multiple sclerosis (MS). The "Early Highly-effective" arm will start with highly effective therapies, such as Ocrevus and Tysabri. Previous studies have shown that these therapies can improve control over the disease's progression and lead to better outcomes. In contrast, the "Escalation" arm will begin with less powerful drugs, switching to stronger ones if needed. Research suggests that starting with these escalation therapies may be less effective initially. The trial aims to determine if using the most effective treatments from the start can manage MS more successfully over time. ^{1 2 6 7 8}

Who Is on the Research Team?

Nikos Evangelou, MD, DPhil

Principal Investigator

University of Nottingham

Daniel Ontaneda, MD, PhD

Principal Investigator

The Cleveland Clinic

Are You a Good Fit for This Trial?

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 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.

I have had at least one MS flare-up or new brain/spine lesions in the last 18 months.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03535298

NCT03535298 | Determining the Effectiveness of earLy ... The DELIVER-MS study seeks to answer the question: Does early treatment with highly effective DMT improve the prognosis for people with MS?

2. msard-journal.com msard-journal.com/article/S2211-0348(25)00432-8/fulltext

Evolution of high-efficacy treatment strategy for relapsing- ... These results witness a change in decision-making regarding the prescription of the initial DMT in RR-MS by neurologists between 2007 and 2022.

3. jamanetwork.com jamanetwork.com/journals/jamaneurology/fullarticle/2806000

Rituximab vs Ocrelizumab in Relapsing-Remitting Multiple ... Rituximab was not noninferior to ocrelizumab, and rituximab treatment was associated with a higher rate and risk of relapse.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10769939/

Multiple sclerosis: time for early treatment with high-efficacy ... MS patients derive greater benefit when therapy is initiated with high-efficacy treatment agents (HETA).

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6534637/

An Overview of High-Efficacy Drugs for Multiple Sclerosis This article discusses the opinions of the multiple sclerosis (MS) experts in the Gulf region on the use of high-efficacy disease-modifying drugs (DMDs)

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10960977/

Shifting from the treat-to-target to the early highly effective ... While both ofatumumab and natalizumab show a good safety profile overall, natalizumab, similarly to ocrelizumab, requires IV administration ...

7. msard-journal.com msard-journal.com/article/S2211-0348(25)00444-4/fulltext

Effect of early highly effective treatment compared to an ... Initiating treatment of persons with MS preferentially with a highly effective DMT at diagnosis reduced the risk of having a new MRI lesion ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0022510X25001947

Ocrelizumab as first-line therapy in highly active relapsing ... As a first-line treatment of highly active RRMS, ocrelizumab demonstrated significant efficacy and very good tolerability.