Personalized Targeted Therapies in Inflammatory Complex Multi Organ Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 2
- 主要终点
- Composite clinico-biological evaluation
研究概览
简要总结
Inflammatory diseases may display atypical features making such patients impossible to classify. Management of these cases in daily practice cannot rely on the results of clinical trials nor on guidelines. DNA and RNA mapping have become major tools to understand and sometimes direct the treatment strategy in oncology. This study aims to test whether a precise analysis of molecular pathways in inflammatory, non classified diseases, can constitute a predictive tool of therapeutic efficiency
详细描述
This is a phase IIb study. The main objective of this study is to evaluate the efficacy of targeted treatments in patients displaying a non-classified, severe and resistant inflammatory disease. Targeted treatments for each patient will have been selected through an algorithm based on molecular analysis of specific altered inflammatory signaling pathway.
Treatments consist in targeted therapies approved in other indications (Kineret®, Humira®, Stelara®, Cosentyx®, Roactemra® and Rituximab®) that will be given once selected using molecular analysis and decision making procedure by the Scientific committee.
For each patient, one targeted treatment will be administered according to the SmPC procedure for a treatment period of 6 months.
Primary efficacy endpoint:
Response will be assessed at month 6 with a composite endpoint defined as improvement of at least 2 of the 3 following parameters:
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
- 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 (men or women) aged 18 years old and over
- •Patients presenting inflammatory non classified disease targeting at least 2 organs involvement: skin, lymph nodes, hemopoietic system, joints, digestive tract, eye, nerves and brain tissues, respiratory tract, cardio-vascular disorders, genito-urinary tract including kidney, musculo-skeletal tissues. Skin involvement is mandatory in order to be able to compare involved and non-involved tissue
- •Signed informed consent
- •The disease should be considered as non-classified despite classical and adapted investigations and evaluation through expert committee meeting.
- •The disease alters significantly quality of life. The impairment of quality of life will be assessed based on the investigator's assessment.
- •The disease has been resistant to at least two prior lines of treatment [for example : Hydroxychloroquine, Chloroquine, Colchicine, Methotrexate, Ciclosporine, Azathioprine, Mycophenolate mofetil, Disulone, Corticosteroids (prednisone, prednisolone, dexamethasone, methylprednisolone…)].
排除标准
- •Patients presenting disease which is not featured by lesional and healthy skin areas, easy to biopsy
- •Patients refusing biopsies
- •Pregnancy
- •Women of child-bearing potential unable to receive highly efficient contraception such as combined oral contraceptives, intra-uterine disposals, hormonal implants or the use of male condoms recommended in case of unstable or irregular partner or as a replacement method for transient unacessebility to hormonal method
- •Breastfeeding
- •Patients presenting disease needing urgent therapeutic measures
- •Patients without health insurance or social security
- •Participation in another interventional trial
- •Patients under legal protection
- •Patients unable to respect the wash out delay of previously taken medications before biopsy and before treatment initiation :
- •Hydroxychloroquine (wash out period = 30 days)
- •Chloroquine (wash out period = 7 days)
- •Colchicine (wash out period = 7 days)
- •Methotrexate (wash out period = 7 days)
- •Ciclosporine (wash out period = 14 days)
- •Azathioprine (wash out period = 14 days)
- •Mycophenolate mofetil (wash out period = 14 days)
- •Disulone (wash out period = 7 days)
- •Corticosteroids (=prednisone, prednisolone, dexamethasone, methylprednisolone) (wash out period = 7 days for doses greater than 5mg)
- •Patients with contra-indications to treatments : Severe or active infections including tuberculosis
研究组 & 干预措施
Cosentyx
干预措施: Cosentyx (Drug)
Kineret
干预措施: Kineret (Drug)
Humira
干预措施: Humira (Drug)
Stelara
干预措施: Stelara (Drug)
Roactemra
干预措施: Roactemra (Drug)
Rituximab
干预措施: Rituximab (Drug)
结局指标
主要结局
Composite clinico-biological evaluation
时间窗: 6 months
Response will be assessed at month 6 with a composite endpoint defined as improvement of at least of 2 of the 3 following parameters: * 50% improvement of the systemic activity assessed by the clinician following a visual analog scale (0-10), where clinician will be asked the following question: "Please indicate, according to your clinical experience and taking into account all systemic manifestations, the level of disease activity in this patient using the following scale:" * and/or 50% improvement of cutaneous activity assessed by the involved skin surface area (according the rule of 9%). Standardised skin pictures will be done in order to centrally review cutaneous response. * and/or 50% decrease or normalisation of biological markers of inflammation (either CRP, ESR or fibrin)
次要结局
- Change in Fibrin(12 months)
- Change in Physician Global Assessment (PGA)(6 months,)
- Change in Systemic Lupus Erythematosus Responder Index (SRI)(12 months)
- Number of Infections(12 months)
- kidney cell count toxicities(12 months)
- blood cell count toxicities(12 months)
- Change in British Isles Lupus Assessment Group (BILAG)(12 months)
- Change in Cutaneous Lupus Disease Area and Severity Index (CLASI)(12 months)
- Change in 36-Item Short Form Health Survey (SF36)(12 months)
- RNA analysis of targeted cytokines and RNA sequencing(6 months)
- Change in CRP(12 months)
- liver cell count toxicities(12 months)
- Change in continuous PGA(12 months)
- Change in ESR (Erythrocyte sedimentation rate)(12 months)
- Decreased in serum increased cytokines, in selected RNA in peripheral blood and skin specimens(12 months)
- Change in CRP(3 months)
- Change in CRP(6 months)
- Change in CRP(9 months)
- Change in Fibrin(6 months)
- Change in Fibrin(9 months)
- Change in Physician Global Assessment (PGA)(1 month,)
- Change in Physician Global Assessment (PGA)(3 months,)
- Change in continuous PGA(9 months)
- Change in British Isles Lupus Assessment Group (BILAG)(3 months)
- Change in British Isles Lupus Assessment Group (BILAG)(6 months)
- Change in British Isles Lupus Assessment Group (BILAG)(9 months)
- Change in Systemic Lupus Erythematosus Responder Index (SRI)(3 months)
- Change in Systemic Lupus Erythematosus Responder Index (SRI)(6 months)
- Change in Systemic Lupus Erythematosus Responder Index (SRI)(9 months)
- Change in Cutaneous Lupus Disease Area and Severity Index (CLASI)(3 months)
- Change in Cutaneous Lupus Disease Area and Severity Index (CLASI)(6 months)
- Change in Cutaneous Lupus Disease Area and Severity Index (CLASI)(9 months)
- Change in 36-Item Short Form Health Survey (SF36)(3 months)
- Change in 36-Item Short Form Health Survey (SF36)(6 months)
- Change in 36-Item Short Form Health Survey (SF36)(9 months)
- Change in CRP(1 month)
- Change in ESR (Erythrocyte sedimentation rate)(1 month)
- Change in ESR (Erythrocyte sedimentation rate)(3 months)
- Change in ESR (Erythrocyte sedimentation rate)(6 months)
- Change in ESR (Erythrocyte sedimentation rate)(9 months)
- Change in Fibrin(1 month,)
- Change in Fibrin(3 months)
- Decreased in serum increased cytokines, in selected RNA in peripheral blood and skin specimens(1 month)
- Decreased in serum increased cytokines, in selected RNA in peripheral blood and skin specimens(3 months)
- Decreased in serum increased cytokines, in selected RNA in peripheral blood and skin specimens(6 months)