A Randomized, Double-blind, Placebo-controlled Phase II Clinical Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetic Profile of Genakumab Injection in Patients With Connective Tissue Disease-associated Interstitial Lung Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 4
- 主要终点
- Lung function assessment:Subjects' lung function was assessed by DLCO.
研究概览
简要总结
This study was conducted in a randomized, double-blind, placebo-controlled design to evaluate the efficacy and safety of Genakumab injection in the treatment of CTD-ILD including Rheumatoid Arthritis associated Interstitial Lung Disease (RA-ILD) and Systemic Sclerosis associated Interstitial Lung Disease (SSc-ILD)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Those who voluntarily sign informed consent and can complete the experiment according to the plan;
- •Age 18-75 years old (including upper and lower limits), both male and female;
- •Rheumatoid arthritis (RA) diagnosed according to the 2010 American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) classification, or Systemic sclerosis (SSc) according to the 2013 ACR/EULAR classification;
- •Interstitial lung disease (ILD) was confirmed by HRCT within 12 months before screening.
- •FVC≥ 40% of the expected value during the screening period;
- •DLCO (using hemoglobin correction) ≥ 40% of the expected value during the screening period;
- •Patients may receive 1 immunosuppressant and must maintain a stable dose for 3 months prior to the first dose and agree to maintain a stable dose for at least 6 months after the first dose;
- •Subjects of childbearing age who do not plan to become pregnant or donate sperm/eggs and agree to use reliable contraception during the period of participation in this trial and within 6 months after the last dosing.
排除标准
- •Allergic to experimental drugs or biological agents; People who have previously known other severe allergic reactions;
- •Airway obstruction (FEV1/FVC<0.7 before bronchodilator use) or other lung abnormalities deemed clinically significant by the investigator or a history of asthma;
- •Those who have received any of the following drugs or treatments :
- •Receiving prednisone >15mg/ day or equivalent dose of glucocorticoid within 2 weeks prior to randomization;
- •Receive azathioprine, colchicine, D-penicillamine, sulfasalazine within 8 weeks before randomization;
- •received rituximab, tolizumab, nidanib, pirfenidone and other treatments within 6 months before randomization; Abacil, TNF inhibitors and other biologic agents were received within 3 months before randomization; Tofaciib, tacrolimus, cyclosporin A, and potassium para-aminobenzoate were used 30 days or 5 half-lives prior to screening, whichever was older.
- •Combined with other rheumatic diseases, such as idiopathic inflammatory myopathy, systemic lupus erythematosus, Sjogren's syndrome, mixed connective tissue disease, systemic vasculitis;
- •Significant pulmonary hypertension, meeting one of the following conditions:
- •Previous clinical or echocardiographic evidence of significant right heart failure;
- •Right cardiac catheterization showed cardiac index ≤ 2 l/min/m2;
- •Pulmonary hypertension requiring extraenteral treatment with eprostol/traprostacycline;
- •There are active bleeding diseases of internal organs, or have a serious bleeding tendency (such as hemophilia, etc.), or are undergoing anticoagulant treatment;
- •There are infections requiring systemic drug control within 7 days prior to screening; Diagnosed with active tuberculosis infection;
- •Have received live or attenuated vaccine within 3 months prior to screening, or plan to receive live or attenuated vaccine during the study period; Vaccination against COVID-19 within 2 weeks prior to screening;
- •Previous stem cell therapy or any type of bone marrow transplant; Previous solid organ transplants; Long-term systemic use of glucocorticoids for other diseases;
- •There is a history of serious immunodeficiency, or other acquired or congenital immunodeficiency diseases;
- •History of malignant tumor within 5 years before screening;
- •Recipients of kidney dialysis;
- •Presence of the following clinically significant heart diseases:
- •A history of chronic congestive heart failure, NYHA level IV; History of cardiac ejection fraction (EF) < 30% by echocardiography;
- •Myocardial infarction, acute coronary syndrome, viral myocarditis, and pulmonary embolism occurred within 3 months; Coronary revascularization was performed within 6 months.
- •There are severe arrhythmias that require Class Ia or III antiarrhythmic drugs; Arrhythmias with diseased sinus syndrome, grade II type II or grade III atrioventricular block, and no pacemaker implanted;
- •During the screening period, electrocardiogram indicated QTcF interval ≥ 480 ms (according to Fridericia correction formula, where QTcF=QT/RR^0.33), or a history of prolonged QTc interval;
- •There are the following abnormalities in the laboratory test values during the screening period:
- •White blood cell count <3×109/L, neutrophil count <1.5×109/L;
- •PLT<75×109/L;
- •Total bilirubin >1.5×ULN, alanine aminotransferase (ALT) >3×ULN, aspartate aminotransferase (AST) >3×ULN;
- •Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2;
- •History or current positive results of serum virology tests:
- •hepatitis B surface antigen positive, or hepatitis B core antibody positive and HBV-DNA higher than the detection limit;
- •Hepatitis C virus (HCV) antibody positive;
- •Positive for human immunodeficiency virus (HIV) antibodies;
- •Those who are positive for treponema pallidum antibodies and need treatment for syphilis infection.
- •Received treatment with any investigational drug or medical device in a clinical trial within 3 months prior to screening;
- •Pregnancy test positive during screening period; Lactating women;
- •The investigator assessed those who had other factors that made them unsuitable for participation in the trial
研究组 & 干预措施
GenSci048
- Dosage: 300 mg.2. Duration of administration: All subjects received one dose of Genakumab injection every 4 weeks according to their group.The dose was injected subcutaneously.3. Course of administration: Phase I subjects were treated with Genakumab injection until the end of the study or the occurrence of the drug.Tolerable toxicity or investigator-assessed efficacy (whichever occurs first); The phase 2 randomized double-blind treatment period was 24 weeks, with a total of 6 administration times. After the randomized double-blind treatment period, an open-label treatment period was entered, and all subjects will receive Genakumab injection 300 mg Q4W until the end of the study or the occurrence of intolerable toxicity or poor efficacy assessed by the investigators (whichever occurs first).4. Administration method: subcutaneous injection; The injection site is the abdomen (3 cm away from the navel
干预措施: GenSci048 (Drug)
GenSci048 placebo
.1. Dosage: 300 mg.2. Duration of administration: All subjects received one dose of placebo every 4 weeks according to their group The dose was injected subcutaneously.3. Course of administration: Phase I subjects were treated with placebo until the end of the study or the occurrence of the drug.Tolerable toxicity or investigator-assessed efficacy (whichever occurs first); The phase 2 randomized double-blind treatment period was 24 weeks, with a total of 6 administration times. After the randomized double-blind treatment period, an open-label treatment period was entered, and all subjects will receive placebo 300 mg Q4W until the end of the study or the occurrence of intolerable toxicity or poor efficacy assessed by the investigators (whichever occurs first).
- Administration method: subcutaneous injection; The injection site is the abdomen (3 cm away from the navel)
干预措施: GenSci048 placebo (Drug)
结局指标
主要结局
Lung function assessment:Subjects' lung function was assessed by DLCO.
时间窗: DLCO will be evaluated simultaneously during the screening period, 4 weeks, 12 weeks, 24 weeks, 36 weeks, 48 weeks, and once every 24 weeks thereafter, From baseline up to 2 years，early withdrawal/termination of treatment, and when the investigator deems
Safety evaluation indicator：Adverse Events
时间窗: From baseline up to approximately 2 years
Lung function assessment:Subjects' lung function was assessed by FVC .
时间窗: FVC will be evaluated simultaneously during the screening period, 4 weeks, 12 weeks, 24 weeks, 36 weeks, 48 weeks, and once every 24 weeks thereafter, From baseline up to 2 years
tLung function assessment:Visual simulation score was used to evaluate Physician's Global Asseessment（PGA）
时间窗: "Lung function assessment:The PGA is evaluated during the screening period and once every 12 weeks .From baseline up to 2 years.
次要结局
未报告次要终点