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

Обзор

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)

Вмешательства

• Препарат GenSci048
  1\. 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
• Препарат 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 randomi

Первичные конечные точки

• Lung function assessment:Subjects' lung function was assessed by FVC . [Срок оценки: 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]
• Lung function assessment:Subjects' lung function was assessed by DLCO. [Срок оценки: 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]
• tLung function assessment:Visual simulation score was used to evaluate Physician's Global Asseessment（PGA） [Срок оценки: "Lung function assessment:The PGA is evaluated during the screening period and once every 12 weeks .From baseline up to 2 years.]
• Safety evaluation indicator：Adverse Events [Срок оценки: From baseline up to approximately 2 years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Другое

Центры проведения

Китай · 4 центра

• Peking University Third Hospital — Пекин
• Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Te — Ухань
• Qilu Hospital of Shandong University — Цзинань
• West China Hospital of Sichuan University — Чэнду

Идентификаторы

NCT: NCT06189495 · GenSci048-204

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗