An Open Label Extension Study of Brentuximab Vedotin Treatment in Active Diffuse Cutaneous Systemic Sclerosis (Diffuse Scleroderma)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Change in skin thickness measured by modified Rodnan Skin Score
研究概览
简要总结
The purpose of this study is to assess safety and efficacy of Brentuximab vedotin, a CD30-directed antibody-drug conjugate, in patients with active diffuse cutaneous systemic sclerosis (dcSSc) who relapsed after discontinuation of Brentuximab vedotin.
详细描述
Systemic sclerosis (SSc, Scleroderma) is a multisystem autoimmune disease characterized by widespread vascular injury and progressive fibrosis of the skin and internal organs. Internal organ involvement results in increased mortality of SSc patients. There is no effective treatment for the majority of patients with early active diffuse scleroderma (diffuse cutaneous systemic sclerosis; dcSSc). It's possible to reverse immune inflammation and reduce the probability of irreversible fibrosis early in the disease course via significant immune modulation. The preliminary results of the Phase II study of Brentuximab vedotin (Protocol BV201708) in SSc demonstrated the short-term safety and benefits of this treatment as many participants already achieved the primary endpoint at 24 weeks. This study is proposed as an extension of the ongoing protocol for up to 48 weeks to make the treatment available for SSc patients who have significantly improved on Brentuximab vedotin, but relapsed after discontinuation of the treatment. Similar to the ongoing Phase II study, the Health Assessment Questionnaire Disability Index (HAQ-DI), patient and physician global scores, inflammatory markers (ESR, CRP), and combined response index in SSc (CRISS) and changes in CD30-stained cells on skin biopsies with IHC will all be exploratory outcomes.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with diffuse cutaneous systemic sclerosis enrolled in the Phase II Adcetris study (BV201708) at St. Joseph's Health centre, aged 18 years or older, and:
- •Worsening mRSS of ≥ 4 points as compared to mRSS score at the end of treatment visit (week 48) in the initial study (BV201708).
- •Able to give informed consent.
排除标准
- •Poor pulmonary function (FVC<40% and/or DLCO<30%).
- •Pregnancy, breast feeding or child bearing potential without practicing highly effective contraception (and partners for men in the study).
- •Clinically significant pulmonary hypertension requiring drug therapy.
- •Clinically significant cardiac disease.
- •Chronic or ongoing active infectious disease requiring systemic treatment.
- •Seropositivity for human immunodeficiency virus (HIV).
- •Active tuberculosis (TB) infection.
- •Active viral infection with viral replication of hepatitis B or C virus.
- •Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, pancreatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease; and cancer.
- •Peripheral neuropathy at screening Grade 2 or higher.
- •Known or suspected hypersensitivity to components of the treatment
- •Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder)
- •Any of the following laboratory abnormalities at screening:
- •Absolute neutrophils count <2.0 x 109/L
- •Hemoglobin <85 g/L
- •Platelet count < 100 x 109/L
- •AST/SGOT or ALT/SGPT >2.0 UNL
- •Participation in another clinical trial within six weeks before randomization in this study, with the exception of continuation from the initial study BV
- •Use of rituximab within the previous 4 months.
- •Immunization with a live/ attenuated vaccine less than 4 weeks prior to the baseline visit.
- •Current or history of progressive multifocal leukoencephalopathy (PML).
研究组 & 干预措施
Administration of Brentuximab vedotin
Maximum duration of treatment: 48 weeks Maximum dose allowed: 0.6 mg/kg Route of administration: intravenous
干预措施: Brentuximab vedotin (Drug)
结局指标
主要结局
Change in skin thickness measured by modified Rodnan Skin Score
时间窗: 48 weeks
Skin improvement is defined as the mean mRSS decrease of ≥8 points modified Rodnan Skin Score (mRSS): is a standard outcome measure for skin disease in SSc and calculated by measuring skin thickness in 17 different body sites (each site scored 0-3, with a total possible additive score of 51). A higher skin score (or a higher "skin thickness") and progression of this score, is predictive of internal organ involvement and mortality. While a lower or improving (lessening) score is associated with favorable outcomes, including better survival.
次要结局
- Change in Scleroderma Health Assessment Questionnaire (SHAQ)(12, 24, 36, and 48 weeks)
- Change in Forced Vital Capacity (pulmonary function)(24 and 48 weeks*)
- Combined Response Index in diffuse cutaneous systemic sclerosis score (CRISS)(Baseline (week 0), and at 24, 48 weeks)
- Change in skin thickness over time measured by modified Rodnan Skin Score(12 weeks and 36 weeks)
- Change in the diffusing capacity for carbon monoxide (pulmonary function)(24 and 48 weeks*)
- Change in patient global assessment of health status(12, 24, 36, and 48 weeks)
- Change in physician global assessment of disease severity(12, 24, 36, and 48 weeks)
- Change in physician global assessment of disease damage(12, 24, 36, and 48 weeks)
- Change in serum concentrations of Erythrocyte Sedimentation Rate(12, 24, 36, and 48 weeks)
- Change in physician global assessment of disease activity(12, 24, 36, and 48 weeks.)
- Change in serum concentrations C-Reactive Protein(12, 24, 36, and 48 weeks)
研究者
Janet Pope
Head of Rheumatology
Lawson Health Research Institute