A Comparative Study of Efficacy and Safety of Genolar® and Xolar® in Treating Patients With Moderate to Severe Persistent Atopic Bronchial Asthma Inadequately Controlled With Stage 4 GINA (2017) Treatment
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AO GENERIUM
- 入组人数
- 192
- 试验地点
- 46
- 主要终点
- Patients proportion with an investigator rating "excellent" or "good" on the Global Evaluation of Treatment Effectiveness (GETE) scale after 26 weeks of comparative treatment
研究概览
简要总结
This is a randomized, double-blind, comparative, parallel-group study of the efficacy and safety of Genolar® and Xolair® in the treatment of persistent atopic bronchial asthma of moderate and severe course, whose symptoms are insufficiently controlled by the 4-step treatment GINA (2017)
详细描述
There is an increasing incidence of bronchial asthma (BA) and other allergic diseases around the world. Bronchial asthma suffers from 4 to 10% of the world population, in Russian Federation, the incidence of BA across the adult population ranges from 2.2 to 5-7%, in the child population is about 10%.
Severe BA is associated not only with frequent hospitalizations and increased mortality but also with high treatment costs.
As to it, there is a hot button issue of developing new drugs for treating patients not to be achieved effectively with standard therapy. Considering the leading pathogenesis role of IgE-mediated allergy, the use of drugs to block IgE makes it possible to control the disease at the earliest allergic reaction phase of the development. It was shown that the IgE elimination from the mast cells and basophils surface reduced the severity of acute allergic reactions, reduced the allergen-induced late phase of the immune response and infiltration with inflammatory cells. These anti-IgE antibodies effects have been shown in various studies.
Genolar® (omalizumab) (JSC "GENERIUM", the Russian Federation) is a humanized recombinant monoclonal antibody selectively binding to immunoglobulin (IgE) and is a biosimilar of Xolar® ("Novartis Pharma AG", Switzerland).
This III phase study is aimed to compare the effectiveness, safety and immunogenicity of Genolar® (JSC "GENERIUM", Russia) and Xolair® to register of the drug Genolar® (JSC "GENERIUM", the Russian Federation), a lyophilizate for subcutaneous administration, in the Russian Federation.
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
- Double (Participant, Investigator)
盲法说明
Throughout the study, until the end of the comparative treatment study period, neither the investigators nor the patients knew which drug was being administered
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women of the ages between 18 and 75 at the time of the Informed Consent Form signature.
- •A documented diagnosis of bronchial asthma for ≥1 year before the Screening;
- •4th stage of asthma treatment according to GINA (2017) ≥2 months before the Screening;
- •The FEV1 value measured ≥4 hours after the last inhalation of short-acting β2-agonists or ≥12 hours after the last inhalation of long-acting β2-agonists is in the range of ≥40% and ≤80% of the proper value;
- •A positive test result for the obstruction reversibility, which is defined as an increase in FEV1 > 12% and > 200 ml from the baseline value, which is measured if inhaled short-acting β2-agonists are withdrawn for ≥4 hours or long-acting β2-agonists ≥12 hours, after 10-15 minutes after inhalation 200-400 mcg salbutamol or equivalent.
- •Daily PEF variability for 2 weeks before randomization is >10%, which is defined as the PEF amplitude between the maximum and minimum values during the day, expressed as an average daily PEF percentage and averaged over 2 weeks: ([maximum per day value - minimum per day value] / average of the maximum and minimum values per day), averaged over 2 weeks and multiplied by 100%;
- •Insufficiently controlled asthma at the Screening despite the correct inhaler use and good adherence to the 4th stage of bronchial asthma treatment (GINA 2017); and the lack of asthma control reasons are not in concomitant diseases, for example, allergic rhinitis. Insufficiently controlled asthma is defined as ≥1.5 points on the ACQ-5 asthma control questionnaire (Asthma Control Questionnaire);
- •Atopy for common environmental allergens confirmed at the Screening, or documented atopy for common environmental allergens in history.
排除标准
- •The initial concentration of total IgE and body weight do not correspond to the range in the dosing table for omalizumab dose-ranging.
- •Asthma resistant to glucocorticosteroids (inhaled, oral or parenteral).
- •Current smokers, smoker's index (pack / years) >
- •Smoker's index (pack / years) = number of cigarettes smoked per day × smoking experience (years) /
- •Asthma exacerbation during the 4 weeks before randomization.
- •Asthma treatment regimen changes during the Introductory trial period during which the basic therapeutic drug Symbicort Turbuhaler was admitted, until the first injection of study drugs.
- •Skipped the basic inhalations with Symbicort® Turbuhaler® during the introductory period of the trial more than 20%.
- •Patients with severe medical conditions that in the view of the investigator prohibits participation in the study.
- •Pregnant or nursing (lactating) women.
- •Monoclonal antibodies administration within 1 year before taking omalizumab.
- •Hypersensitivity to any of the used study drug, to their components, history of an undesirable drug reaction.
- •A history of autoimmune disease.
结局指标
主要结局
Patients proportion with an investigator rating "excellent" or "good" on the Global Evaluation of Treatment Effectiveness (GETE) scale after 26 weeks of comparative treatment
时间窗: In 26 weeks after comparative treatment beginning (Genolar® vs. Xolair®)
Global evaluation of treatment effectiveness (GETE) is a validated tool and has been used to evaluate the clinical response to omalizumab in patients with moderate to severe allergic asthma (IgE-mediated).
次要结局
- FEV1 changes from FEV1 baseline at each visit over 26 weeks of comparative treatment (Genolar® vs. Xolair®)(At the screening, for the Introductory trial period during which the basic therapeutic drug Symbicort Turbuhaler was admitted, before the comparative treatment beginning, in 8, 16, 26 weeks of comparative treatment (Genolar® vs. Xolair®))
- Number of days without asthma symptoms during the 26-week period of comparison treatment (Genolar® vs. Xolair®)(For 26 weeks of comparative treatment (Genolar® vs. Xolair®))
- The number of bronchial asthma exacerbations per patient for 26-week period of comparative treatment(For 26 weeks after comparative treatment start (Genolar® vs. Xolair®))
- Neutralizing antibody rate(Baseline, in 6, 26, 52 weeks of treatment)
- Mean PEF change in every 4 weeks compared to PEF baseline in patients treated with Genolar® and Xolar® for 26 weeks of comparative treatment(Every 4 weeks for 26 weeks of comparative treatment (Genolar® vs. Xolair®))
- Patients proportion with an ACQ-5 Asthma Control Questionnaire score ≤0.75 after 26 weeks of treatment(At the screening, before the comparative treatment start, upon 26 weeks of comparative treatment (Genolar® vs. Xolair®) completion)