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

Launched by CHANGCHUN GENESCIENCE PHARMACEUTICAL CO., LTD. · Dec 19, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called Genakumab injection for patients with certain lung diseases related to connective tissue diseases, specifically those associated with rheumatoid arthritis and systemic sclerosis. The trial aims to see how safe and effective this treatment is in helping patients breathe better and manage their symptoms.

To participate, candidates must be between 18 and 75 years old and have a confirmed diagnosis of rheumatoid arthritis or systemic sclerosis, along with specific lung issues verified by a recent scan. Participants will receive either the Genakumab injection or a placebo (a treatment that looks like the real one but has no active ingredients) without knowing which one they are getting, which helps ensure the results are unbiased. Throughout the study, participants will be monitored for any side effects and how well the treatment is working. If you're interested in joining, make sure to discuss it with your healthcare provider to see if you meet the eligibility criteria and understand what to expect during the trial.

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Eligibility criteria

• Inclusion Criteria:
• • 1. Those who voluntarily sign informed consent and can complete the experiment according to the plan;
• • 2. Age 18-75 years old (including upper and lower limits), both male and female;
• • 3. 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;
• • 4. Interstitial lung disease (ILD) was confirmed by HRCT within 12 months before screening.
• • 5. FVC≥ 40% of the expected value during the screening period;
• • 6. DLCO (using hemoglobin correction) ≥ 40% of the expected value during the screening period;
• • 7. 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;
• • 8. 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.
• Exclusion Criteria:
• • 1. Allergic to experimental drugs or biological agents; People who have previously known other severe allergic reactions;
• • 2. Airway obstruction (FEV1/FVC\<0.7 before bronchodilator use) or other lung abnormalities deemed clinically significant by the investigator or a history of asthma;
• 3. Those who have received any of the following drugs or treatments :
• • 1. Receiving prednisone \>15mg/ day or equivalent dose of glucocorticoid within 2 weeks prior to randomization;
• • 2. Receive azathioprine, colchicine, D-penicillamine, sulfasalazine within 8 weeks before randomization;
• • 3. 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.
• • 4. Combined with other rheumatic diseases, such as idiopathic inflammatory myopathy, systemic lupus erythematosus, Sjogren's syndrome, mixed connective tissue disease, systemic vasculitis;
• 5. Significant pulmonary hypertension, meeting one of the following conditions:
• • 1. Previous clinical or echocardiographic evidence of significant right heart failure;
• • 2. Right cardiac catheterization showed cardiac index ≤ 2 l/min/m2;
• • 3. Pulmonary hypertension requiring extraenteral treatment with eprostol/traprostacycline;
• • 6. There are active bleeding diseases of internal organs, or have a serious bleeding tendency (such as hemophilia, etc.), or are undergoing anticoagulant treatment;
• • 7. There are infections requiring systemic drug control within 7 days prior to screening; Diagnosed with active tuberculosis infection;
• • 8. 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;
• • 9. Previous stem cell therapy or any type of bone marrow transplant; Previous solid organ transplants; Long-term systemic use of glucocorticoids for other diseases;
• • 10. There is a history of serious immunodeficiency, or other acquired or congenital immunodeficiency diseases;
• • 11. History of malignant tumor within 5 years before screening;
• • 12. Recipients of kidney dialysis;
• 13. Presence of the following clinically significant heart diseases:
• • 1. A history of chronic congestive heart failure, NYHA level IV; History of cardiac ejection fraction (EF) \< 30% by echocardiography;
• • 2. Myocardial infarction, acute coronary syndrome, viral myocarditis, and pulmonary embolism occurred within 3 months; Coronary revascularization was performed within 6 months.
• • 3. 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;
• • 4. 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;
• 14. There are the following abnormalities in the laboratory test values during the screening period:
• • 1. White blood cell count \<3×109/L, neutrophil count \<1.5×109/L;
• • 2. PLT\<75×109/L;
• • 3. Total bilirubin \>1.5×ULN, alanine aminotransferase (ALT) \>3×ULN, aspartate aminotransferase (AST) \>3×ULN;
• • 4. Estimated glomerular filtration rate (eGFR) \< 60 ml/min/1.73m2;
• 15. History or current positive results of serum virology tests:
• • 1. hepatitis B surface antigen positive, or hepatitis B core antibody positive and HBV-DNA higher than the detection limit;
• • 2. Hepatitis C virus (HCV) antibody positive;
• • 3. Positive for human immunodeficiency virus (HIV) antibodies;
• • 4. Those who are positive for treponema pallidum antibodies and need treatment for syphilis infection.
• • 16. Received treatment with any investigational drug or medical device in a clinical trial within 3 months prior to screening;
• • 17. Pregnancy test positive during screening period; Lactating women;
• • 18. The investigator assessed those who had other factors that made them unsuitable for participation in the trial