A Multicenter Prospective Randomized Comparative Study of Pharmacokinetics, Clinical Efficacy and Safety of Tigerase® (JSC GENERIUM, Russia) vs. Pulmozyme® (Hoffmann-La Roche, Switzerland) as Part of Complex Therapy in Patients With Cystic Fibrosis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AO GENERIUM
- 入组人数
- 100
- 试验地点
- 26
- 主要终点
- Change in forced expiratory volume in the first second of a forced expiratory maneuver (FEV1) compared to baseline
研究概览
简要总结
It is a multicenter, open-label, randomized, parallel-group study of the efficacy and safety of Tigerase® compared Pulmozyme® in patients with Cystic Fibrosis
详细描述
Cystic fibrosis (CF) is a common hereditary disease with an autosomal recessive type of inheritance, characterized by systemic damage to the exocrine glands, mainly the bronchopulmonary and gastrointestinal systems. CF is usually characterized by a severe course and poor prognosis. The severity of the disease and the life expectancy of the patient with CF is determined primarily by the state of the bronchopulmonary system; more than 90% of patients die from lung diseases.
CF Pulmonary damage develops as a result of a gene mutation - cystic fibrosis transmembrane regulator of ion conductivity Na and Cl (CFTR-cystic fibrosis transmembrane regulator). The main function of CFTR is to regulate the transport of sodium and chlorine across the cell membrane and is part of the cAMP-dependent chlorine channel. CFTR-protein dysfunction in the bronchial tree epithelial cells leads to a blockage of the chlorine ions transport and an increase in the sodium ions absorption, and impaired fluid secretion through the epithelial cells apical membrane.
Dornase alpha, a human recombinant deoxyribonuclease 1 (rhDNase, rhDNase) hydrolyzes extracellular DNA (viscous polyanion) that enters the sputum from destroyed neutrophils, thereby reducing the adhesion and viscosity of sputum. In CF patients dornase alpha is used as symptomatic therapy in combination with standard therapy in patients with a forced vital capacity (FVC) index of at least 40% of the proper value.
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
- •Signed Patient Informed Consent Form for participation in the study;
- •Men and women 18 years and older;
- •Diagnosis of cystic fibrosis, defined as the presence of disease symptoms and a positive sweat test and / or detection of 2 mutations of the MVTR gene during genotyping;
- •FEV1 ≥40% and ≤100% of the proper value;
- •The ability to understand the protocol requirements, to give written consent to participate in the study (including the use and transfer of information about the patient's health status related to the study).
排除标准
- •Hypersensitivity to any of used study drug, to their components, as well as a history of significant allergic reactions;
- •Acute respiratory infection or exacerbation of chronic pulmonary disease within 4 weeks prior to screening and without corticosteroid or antibiotic therapy;
- •Concomitant diseases and conditions with potential impact the patients safety, including:
- •Severe renal impairment (serum creatinine more than 1.5 times higher than the upper limit of normal);
- •Severe liver impairment (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) blood serum activity is 2.5 times or more higher than the upper limit of the laboratory norm);
- •A history of lung transplantation or planned transplantation during this study;
- •The presence of antibodies to HIV, active viral hepatitis B and / or C and / or cirrhosis in the history or detected on Screening;
- •Pregnancy and lactation;
- •Refusal of patients with preserved reproductive potential to use adequate contraception throughout the study and within 30 days after the end of the study;
- •Patients who underwent a blood or blood components transfusion within 10 days prior to screening;
- •Drug or alcohol abuse at the time of Screening or in the past;
- •Patient's participation in any other clinical trials and / or administration of an experimental drug within 30 days prior to the Screening Visit.
结局指标
主要结局
Change in forced expiratory volume in the first second of a forced expiratory maneuver (FEV1) compared to baseline
时间窗: FEV1 - forced expiratory volume in the first second of a forced expiratory maneuver by standard spirometry
Week 24 ± 1
次要结局
- The number of days before the chronic pulmonary disease exacerbation development(Week 24 ± 1)
- Change in body weight compared to baseline(Week 24 ± 1)
- Change in the average score for the "Symptoms", "Activity", "Influence" subscales, as well as the average total score of the St. George's Respiratory Questionnaire (SGRQ), version 2.2(Week 24 ± 1)
- Change in forced lung capacity (FVC) compared to baseline(Week 24 ± 1)
- The number of exacerbations of chronic pulmonary disease(Week 24 ± 1)