Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for the Treatment of Relapsing-Remitting Multiple Sclerosis
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 800
- 试验地点
- 60
- 主要终点
- Brain volume loss, baseline to month 36
研究概览
简要总结
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.
详细描述
DELIVER-MS is a multi-center pragmatic comparative effectiveness randomized clinical trial with additional-parallel observational cohort. It aims to enroll up to 400 individuals newly diagnosed with RRMS and randomize them 1:1 to Early Highly Effective (EHT) or Escalation (ESC) treatment paradigms, based on the use of different disease modifying therapies (DMT) as first-line therapy. EHT approach to DMT is defined as use of one of five monoclonal antibodies (alemtuzumab, natalizumab, rituximab, ocrelizumab, ofatumumab, ublituximab) as first-line therapy. ESC approach is defined as initiating any other approved MS DMT as first-line therapy, then escalating to a more effective therapy upon disease activity. Once randomized, the Neurologist and Participant decide which DMT within the arm is most appropriate. After the initial DMT is initiated, if a DMT change is needed, the second-line therapy may be chosen from either arm, regardless of randomization. The randomization only applies to the initial DMT choice.
Up to 400 individuals who do are not amenable to randomization or who agree to randomization but are not approved for coverage for a medication in the arm to which they were randomized will enter the Observational Arm. In the Observational Arm, the DMT chosen is from any approved DMT for MS and is chosen by the Neurologist and participant.
All study procedures throughout are identical between the randomized and observation alarm, except for the randomization.
The primary objective for the initial 36 months of the study is normalized whole brain volume loss, measured using MRI from baseline to Month 36. The primary objective for the long term extension of the study (Months 48-108) is the EDSS+, a composite measure of clinical disability based on the EDSS and MSFC.
The study is performed primarily in tertiary MS Centers in the US and UK.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Escalation Therapies Group (Drug)
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.
干预措施: Early Highly Effective Therapies Group (Drug)
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.
结局指标
主要结局
Brain volume loss, baseline to month 36
时间窗: 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, baseline to month 36
时间窗: 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.
EDSS+, month 48 to month 108
时间窗: 48 months to 108 months
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.
次要结局
- Brain volume loss, month 6 to month 36(Month 6 to month 36)
- Proportion of participants with progression(Baseline to 36 months)
- Change in MSIS-29, baseline to 36 months(Baseline to 36 months)
- Change in Neuro-QOL, baseline to 36 months(Baseline to 36 months)
- Brain volume loss, month 6 to month 36(Month 6 to month 36)
- Proportion of participants with progression(Baseline to 36 months)
- Change in MSIS-29, baseline to 36 months(Baseline to 36 months)
- Change in Neuro-QOL, baseline to 36 months(Baseline to 36 months)
- Time to reach SPMS, month 48 to month 108(48 months to 108 months)
- Efficacy difference between EHT and ESC, month 48 to month 108(48 months to 108 months)
- Safety difference between EHT and ESC, month 48 to month 108(48 months to 108 months)
研究者
Daniel Ontaneda, MD
Principal Investigator
The Cleveland Clinic