Keratinocyte Growth Factor - Promoting Thymic Reconstitution and Preventing Autoimmunity After Alemtuzumab (Campath-1H) Treatment of Multiple Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- incidence of clinical autoimmunity
研究概览
简要总结
The purpose of this study is to test a novel strategy to prevent the clinical problem of secondary autoimmunity following alemtuzumab treatment of multiple sclerosis.
The hypothesis is that autoimmunity after alemtuzumab can be prevented by giving a drug that promotes thymic T cell regeneration (Palifermin, Kepivance®).
详细描述
This is a single-centre, double-blinded, randomised controlled trial of palifermin (Kepivance) vs. placebo in the prevention of autoimmunity following alemtuzumab treatment of multiple sclerosis.
The dose of palifermin (kepivance)used in this trial will be informed by a dose-escalation study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Months 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or non-pregnant, non-lactating female patients
- •> 18 years of age, and <50 years of age inclusive
- •Diagnosis of MS using McDonald's 2010 criteria, including MRI abnormalities consistent with McDonald's 2010 criteria.
- •Onset of first MS symptoms within 10 years on the date the ICF is signed
- •EDSS score 0.0 to 5.0 (inclusive) at screening
- •At least 2 clinical episodes of MS in the 2 years prior to study entry, with at least 1 attack within 12 months, which may have occurred whilst on disease-modifying therapy, namely any beta interferon or glatiramer acetate.
- •Serum IL-7≤7pg/mL
排除标准
- •Any progressive form of multiple sclerosis
- •Previous thymectomy
- •Previous treatment with alemtuzumab, natalizumab, mitoxantrone, cyclophosphomide, cladribine, rituximab or any other immunosuppressant or cytotoxic therapy (other than steroids and disease-modifying therapies listed above)
- •History of malignancy
- •Personal history of clinically significant autoimmune disease, other than multiple sclerosis (including but not limited to: thyroid disease, immune cytopenias, inflammatory bowel disease, diabetes, lupus, severe asthma)
- •Intolerance of pulsed corticosteroids, especially a history of steroid psychosis
- •Major systemic disease or other illness that would, in the opinion of the investigator, compromise patient safety or interfere with the interpretation of study results.
- •Seropositivity for human immunodeficiency virus (HIV)
- •Past or present hepatitis B infection (positive hepatitis B serology)
- •Pregnant women or male and female patients who do not agree to use effective contraception during the study.
- •Medical, psychiatric, cognitive or other conditions that, in the investigator's opinion, compromise the patient's ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study.
研究组 & 干预措施
Palifermin (and Alemtuzumab)
Palifermin (Kepivance®), at the maximum identified tolerated dose will be administered by intravenous bolus on days -5, -4. -3 prior to, and on days 8, 9 and 10 after each cycle of alemtuzumab, then again on 3 consecutive days at month 1 and month 3 after each cycle of alemtuzumab. Patients will be observed for adverse reactions for at least 1 to 2 hours following each bolus dose. Initial treatment alemtuzumab will be administered as a fixed total dose of 60 mg IV over 5 consecutive days (12mg/day). For re-treatment at Month 12, alemtuzumab will be administered as a fixed total dose of 36mg IV over 3 consecutive days (12mg/day).
干预措施: Palifermin (Drug)
Palifermin (and Alemtuzumab)
Palifermin (Kepivance®), at the maximum identified tolerated dose will be administered by intravenous bolus on days -5, -4. -3 prior to, and on days 8, 9 and 10 after each cycle of alemtuzumab, then again on 3 consecutive days at month 1 and month 3 after each cycle of alemtuzumab. Patients will be observed for adverse reactions for at least 1 to 2 hours following each bolus dose. Initial treatment alemtuzumab will be administered as a fixed total dose of 60 mg IV over 5 consecutive days (12mg/day). For re-treatment at Month 12, alemtuzumab will be administered as a fixed total dose of 36mg IV over 3 consecutive days (12mg/day).
干预措施: Alemtuzumab (Drug)
Placebo (and Alemtuzumab)
Initial treatment alemtuzumab will be administered as a fixed total dose of 60 mg IV over 5 consecutive days (12mg/day). For re-treatment at Month 12, alemtuzumab will be administered as a fixed total dose of 36mg IV over 3 consecutive days (12mg/day).
干预措施: Alemtuzumab (Drug)
结局指标
主要结局
incidence of clinical autoimmunity
时间窗: within 30 months of starting treatment with alemtuzumab
The primary endpoint is incidence of clinical autoimmunity within 30 months of starting treatment with alemtuzumab
次要结局
- Safety events(within 30 months of starting treatment with alemtuzumab)
- Absolute numbers of naive T cells(within 30 months of starting treatment with alemtuzumab)
研究者
Alasdair Coles
Principal Investigator
Cambridge University Hospitals NHS Foundation Trust