Evaluating Genakumab for Lung Disease Related to Connective Tissue Disorders

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

This study is testing whether an injection called Genakumab can help people with lung disease caused by connective tissue disorders like rheumatoid arthritis and systemic sclerosis feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Changchun GeneScience Pharmaceutical Co., Ltd. (Industry-sponsored)
• Drugs / interventions: rituximab, tolizumab, prednisone, Genakumab
• Locations: 4 sites (Beijing, Beijing Municipality and 3 other locations)
• Trial ID: NCT06189495 on ClinicalTrials.gov

What this trial studies

This clinical trial is designed to assess the safety, tolerability, efficacy, and pharmacokinetics of Genakumab injection in patients suffering from connective tissue disease-associated interstitial lung disease, specifically targeting those with rheumatoid arthritis and systemic sclerosis. The study employs a randomized, double-blind, placebo-controlled methodology to ensure unbiased results. Participants will receive either the Genakumab injection or a placebo, and their responses will be closely monitored over the course of the trial.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18-75 with confirmed diagnoses of rheumatoid arthritis or systemic sclerosis and interstitial lung disease.

Not a fit: Patients with interstitial lung disease not associated with connective tissue diseases or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve lung function and quality of life for patients with connective tissue disease-associated interstitial lung disease.

How similar studies have performed: While this approach is being explored in this specific context, similar studies targeting interstitial lung disease have shown promise, indicating potential for success.

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

Where this trial is running

Beijing, Beijing Municipality and 3 other locations

• Peking University Third Hospital — Beijing, Beijing Municipality, China (Recruiting)
• Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)
• Qilu Hospital of Shandong University — Jinan, Shandong, China (Recruiting)
• West China Hospital of Sichuan University — Chengdu, Sichuan, China (Not_yet_recruiting)

Study contacts

• Study coordinator: shengnan wen

Conditions Systemic Sclerosis Associated Interstitial Lung Disease; Rheumatoid Arthritis Associated Interstitial Lung Disease; connective tissue disease-associated interstitial lung disease; Rheumatoid Arthritis associated Interstitial Lung Disease; Systemic Sclerosis associated Interstitial Lung Disease