Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for RRMS (DELIVER-MS)

NeuroTherapia, Inc.

Status and phase: Active, not recruiting; Phase 4

Conditions: Multiple Sclerosis, Relapsing-Remitting

Treatments: Drug: Early Highly Effective Therapies Group; Drug: Escalation Therapies Group

Study type: Interventional

Funder types: Other

Identifiers

NCT03535298

CCF 18-326/23-453

Details and patient eligibility

About

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.

Enrollment: 800 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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800 participants in 3 patient groups

EHT: Early Highly-effective

Experimental group

Description:

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.

Treatment:

Drug: Early Highly Effective Therapies Group

ESC: Escalation

Experimental group

Description:

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.

Treatment:

Drug: Escalation Therapies Group

OBS: Observational

No Intervention group

Description:

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.