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
Overview
- Phase
- Phase 2
- Intervention
- GenSci048
- Conditions
- Systemic Sclerosis Associated Interstitial Lung Disease
- Sponsor
- Changchun GeneScience Pharmaceutical Co., Ltd.
- Enrollment
- 30
- Locations
- 4
- Primary Endpoint
- Lung function assessment:Subjects' lung function was assessed by DLCO.
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
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)
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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;
Arms & Interventions
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 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
Intervention: GenSci048
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). 4. Administration method: subcutaneous injection; The injection site is the abdomen (3 cm away from the navel)
Intervention: GenSci048 placebo
Outcomes
Primary Outcomes
Lung function assessment:Subjects' lung function was assessed by DLCO.
Time Frame: 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
Time Frame: From baseline up to approximately 2 years
Lung function assessment:Subjects' lung function was assessed by FVC .
Time Frame: 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）
Time Frame: "Lung function assessment:The PGA is evaluated during the screening period and once every 12 weeks .From baseline up to 2 years.