Phase II Randomized Double Blind Clinical Trial of'Imatinib Mesylate STI571 (Glivec®) Versus Placebo in Patients With Severe Cutaneous Scleroderma or Systemic Sclerosis With Severe Cutaneous Involvement.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 28
- 试验地点
- 24
- 主要终点
- Compare the efficacy of imatinib mesylate vs placebo based on the percent variation of modified Rodnan score (0-51) between inclusion and 6-month visits.
研究概览
简要总结
In vitro studies have shown that imatinib 1mM inhibits strongly the growth of cutaneous fibroblasts. The hypothesis is that imatinib inhibits PDGFR which is known to be a potential target for the molecule, as recently also proposed after the discovery of autoantibodies activating the PDGF receptors. Recent data indicate that TGFb is also a potential target of imatinib. Cutaneous scleroderma is characterized by progressive cutaneous fibrosis caused by hyperactive dermal fibroblasts. Since no established treatment for skin sclerosis in scleroderma is currently available. This study will test the safety and efficacy of imatinib in the treatment of patients with scleroderma and severe cutaneous involvement.
详细描述
This study will test the efficacy and tolerance of patients with a high score of induration (modified Rodnan score > 20/54) Comparison : 34 patients with severe forms of cutaneous involvement will be evaluated in a double blind RCT comparing imatinib 400mg/j and placebo in a 6 month period. Efficacy will be assessed using a cutaneous induration scale and skin biopsy, and quality of life questionnaires.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •More than 18 years old
- •Documented diagnostic of scleroderma (systemic or cutaneous)
- •Severe cutaneous sclerodermia or systemic sclerodermia with m-Rodnan score > 20/51
- •Ejection fraction of more than 45 per cent at cardiac ultrasound pre-inclusion study
- •Woman with efficient contraceptive method during trail treatment and during 3 month after the end of trial treatment
- •All female patients with reproductive potential must have a negative pregnancy test (serum or urine) within the 7 days prior to enrolment
- •Affiliated or profit patient of a social security system
- •Signed informed consent
排除标准
- •new systemic treatment, potentially interfering with disease progression, beginning 3 months prior the start trial treatment
- •Patient with isolated cutaneous scleroderma treated with a drug potentially interfering with the course of the disease 4 weeks before starting the trial (Systemic corticosteroids, methotrexate, cyclophosphamide, bosentan)
- •Scleroderma " en coup de sabre "
- •Severe organ failure or anomaly of blood chemistry/hematology (bilirubin, SGOT, SGPT, creatinine > 1,5 ´ upper normal limit, polymorphonuclear granulocytes less than 1*10*9/l or platelets less than 50*10*9/l),
- •Ongoing cancer
- •Ejection fraction ≤ 45 per cent at cardiac ultrasound pre inclusion study
- •myocardial infarction of less than 6 mois at pre inclusion visit
- •Non controlled chronic illness (diabetes, chronic kidney failure, chronic hepatitis, HIV infection),
- •Major surgery less than two weeks before inclusion
- •Pregnancy or lactation
- •Absence of validated contraception in childbearing women.
- •Contraindication to imatinib mesylate treatment as specified in product specifications
- •Non observance anticipated and absence of informed consent
研究组 & 干预措施
2
6 month treatment with Placebo 400mg/day
干预措施: imatinib mesylate (Drug)
1
6 month treatment with Imtinib 400mg/day
干预措施: imatinib mesylate (Drug)
结局指标
主要结局
Compare the efficacy of imatinib mesylate vs placebo based on the percent variation of modified Rodnan score (0-51) between inclusion and 6-month visits.
时间窗: 6 month
次要结局
- Compare efficacy of imatinib mesylate vs placebo based on the percent variation of modified Rodnan score between the inclusion and the various time points of follow-up.(1, 3 and 12 month)
- Assess skin thickness at inclusion and at 6 months using skin biopsies(6 month)
- Assessment of quality of life using DLQI (Dermatology Quality of Life Index) and HAQ (Health Assessment Questionnaire).(At 1, 3, 6 month and 1 year,)
- Assess tolerance of treatment (clinical and laboratory monitoring of side effects)(All along the trial)
- Assess effects of treatment on non cutaneous symptoms in systemic sclerosis patients(All along the trial)