Prospective Evaluation of De-Escalation From antiCD-20 Therapies to Dimethyl Fumarate (Tecfidera) or Diroximel Fumarate (Vumerity)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Components of No Evidence of Disease Activity (NEDA-3) components (of which are no relapse activity, no MRI disease activity and no confirmed disability progression).
研究概览
简要总结
The investigators propose a multi-center pilot study, which aims to evaluate safety and efficacy of fumarates as de-escalation therapy in clinically stable MS patients previously treated with anti-CD20 therapy.
详细描述
Ten patients >18 years of age with a minimum of 2 years of MS disease stability (no relapse or new magnetic resonance imaging lesions) and at least one year of experience on an anti-CD20 agent prior to initiating de-escalation with diroximel fumarate (Vumerity®) or dimethyl fumarate (Tecfidera®) will be followed for 24 months post de-escalation. To account for screen failures and withdrawals, up to 15 may be enrolled.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with relapsing forms of MS
- •> 18 years of age at the time of initiation of de-escalation
- •No evidence of new inflammatory disease activity (no new T2/contrast enhancing lesions, absence of relapses) for at least two years prior to de-escalation
- •Have had multiple sclerosis related symptoms at least 3 years prior to baseline visit.
- •Taking an anti-CD20 therapy most recently as a DMT continuously for at least one year (have received at least 2 courses) prior to de-escalation.
- •Are 6-12 months from their last anti-CD20 infusion
- •Willing to follow the protocol
- •Able to undergo a brain MRI without anesthesia
排除标准
- •Any progression of neurological symptoms in the year prior to the screening visit that would be consistent with progressive MS.
- •Use of any non-FDA-approved DMT or systemic corticosteroids in the last 2 years. (Note: Use of inhaled or topical steroids are not an exclusion criteria. Also, use of oral steroids for no greater than 14 days given for a non-MS condition is not exclusionary).
- •IgG levels <300 mg/dL
- •lymphocytes <800 cells/mm3
- •EDSS >6.5
- •Is considering pregnancy at the screening visit
- •Prior use of alemtuzumab, mitoxantrone, cyclophosphamide, methotrexate, cyclosporine or any experimental MS treatment in the last 5 years.
- •Prior allergy to Vumerity
- •Other significant medical or psychiatric illness, if uncontrolled. Examples: uncontrolled hypertension, uncontrolled diabetes, uncontrolled asthma, uncontrolled depression
- •Cancers other than basal cell skin cancers within the last 5 years
- •Unable to give informed consent or follow the protocol.
- •Unable to undergo brain MRI.
- •History of other chronic neurological illnesses that might mimic MS with chronic or intermittent symptoms (i.e. ALS, myasthenia gravis, chronic neuropathy, etc.)
研究组 & 干预措施
De-escalation therapy to diroximmel fumarate (Vumerity®) or dimethyl fumarate (Tecfidera®)
干预措施: Vumerity (Drug)
De-escalation therapy to diroximmel fumarate (Vumerity®) or dimethyl fumarate (Tecfidera®)
干预措施: Tecfidera (Drug)
结局指标
主要结局
Components of No Evidence of Disease Activity (NEDA-3) components (of which are no relapse activity, no MRI disease activity and no confirmed disability progression).
时间窗: From baseline to 24 months
Number of subjects not meeting NEDA defined as: 1. Evidence of Relapse activity - collected via monthly phone calls and study visits. OR 2. MRI disease activity - presence of new lesions (T2 or Gd enhancing) on scans done at baseline, months 12 and 24. OR 3. 6 months Confirmed Disability progression (CDP6): measured by EDSS done at baseline and every 6 months. CDP6 is defined as an increase in EDSS score of ≥1.5 if baseline EDSS was 0; or ≥1.0 points if baseline EDSS was ≥0.5-≤5; or by ≥0.5 points if baseline EDSS ≥6, sustained over two consecutive visits for ≥6 months. The time with NEDA (primary outcome) will be described using product-limit estimates (Kaplan-Meier plots). With 20 patients, if there is no evidence of disease activity in any patients in 24 months, we are 90% confident that the true rate is below 17%. Similarly with 1, 2, and 3 patients with observable disease activity in 24 months, the true rates are between 0.1-25%, 1-32% and 3-38% respectively.
次要结局
- Neurofilament light levels(From baseline to 24 Months)
- Brain parenchymal volume loss (using Icometrix)(From baseline to 24 Months)
- Multiple Sclerosis Functional Composite (MSFC)(From baseline to 24 Months)