The HIt HArd and hiT Early in Multiple Sclerosis Trial - HiHat Trial A Phase 2 Study of Sequential Treatment With Rituximab and Cladribine for Relapsing-remitting Multiple Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 8
- 主要终点
- Treatment-related Serious Adverse Events
研究概览
简要总结
The HiHat trial is a Phase 2 study aimed at evaluating the safety and feasibility of sequential treatment with rituximab and cladribine in patients with relapsing-remitting multiple sclerosis (RRMS). The study follows a prospective, open-label, single-arm design, with 60 RRMS patients receiving both treatments in a controlled regimen: two cycles of rituximab (1,000 mg each, biweekly) followed by two cycles of cladribine (30 mg per cycle for three days per cycle) spaced one month apart. Participants are monitored over 24 months through clinical assessments, MRI, and biomarker analyses. The primary objective is to evaluate whether the rate of serious adverse events (SAE) is acceptably low. Secondary objectives include assessing impacts on MRI lesion count, relapse rates, disability progression, quality of life, and safety.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of RRMS according to the 2017 revised McDonald criteria,
- •With disease activity within the preceding year in the form of: a clinical relapse, and/or evidence of ≥2 T2 lesions on MRI scan, and or presence of gadolinium enhancing lesions on an MRI scan,
- •Age 18 - 50 years (inclusive) of age,
- •Disease duration ≤10 years (since MS diagnosis),
- •EDSS 0 - 5.5 (inclusive),
- •Signed informed consent.
排除标准
- •Diagnosis of progressive MS,
- •Previous use of rituximab (or any other B-cell depleting monoclonal antibody) and/or cladribine,
- •Pregnant or lactating women,
- •Unwilling to use contraception during the treatment period and the first year after completing the treatment course,
- •Patients having contraindication for or otherwise not compliant with MRI investigations,
- •Simultaneous treatment with other immunosuppressive drugs,
- •Infection with human immunodeficiency virus (HIV),
- •Active, severe infections (e.g. hepatitis or tuberculosis),
- •Severe cardiac disorder,
- •Moderate or severe renal impairment (eGFR <60).
- •Active malignancy,
- •No prior exposure to varicella virus,
- •Vaccination within 4 weeks of first dose of study medication,
- •Severe psychiatric condition.
研究组 & 干预措施
Patients with relapsing-remitting multiple sclerosis (RRMS)
The study population will consist of subjects with RRMS with less than 10 years disease duration.
干预措施: Sequential treatment with rituximab and cladribine (Drug)
结局指标
主要结局
Treatment-related Serious Adverse Events
时间窗: From start of treatment until end of follow-up at 2 years.
The primary objective of the study is to evaluate whether the SAE rate associated with sequential treatment of rituximab followed by cladribine is acceptably low. The proportion of patients with at least one treatment-related SAE (relationship ≥ possible) will be reported.
次要结局
- Magnetic Resonance Imaging (MRI) lesions(The first scan made after the treatment course has been completed (week 12) will be compared with the scan at 2 years to determine if new lesions have occurred.)
- Relapses(From start of treatment until the end of follow-up at 2 years.)
- Disability(EDSS at baseline will be compared with EDSS at end of follow-up at 2 years.)
- Symbol Digit Modalities Test (SDMT)(SDMT at baseline is compared with SDMT at end of follow-up at 2 years.)
- Quality of life (physical) measured by MSIS-29 (Multiple Sclerosis Impact Scale)(Baseline compared with end of follow-up at 2 years.)
- Quality of life (MSIS-29 psychological)(Baseline compared with end of follow-up at 2 years.)
- Treatment-related Adverse Events(From start of treatment to end of follow-up at 2 years.)