Systemic sclerosis
Conditions
Interventions
75mg TID Group:Administer orally three times daily (TID).
Each dose: 1 tablet of HY-021068 (75mg) + 2 blank tablets.
Dosing interval: Approximately 8 +/- 2 hours between doses.
Duration: Contin
150mg TID Group:Administer orally three times daily (TID).
Each dose: 2tablet of HY-021068 (150mg) + 1 blank tablets.
Dosing interval: Approximately 8 +/- 2 hours between doses.
Duration: Conti
225mg TID Group:Administer orally three times daily (TID).
Each dose: 3 tablets of HY-021068 (75mg per tablet, totaling 225mg).
Dosing interval: Approximately 8 +/- 2 hours between doses.
Durat
Placebo Group:Administer orally three times daily (TID).
Each dose: 3 blank tablets.
Dosing interval: Approximately 8 +/- 2 hours between doses.
Duration: Continue for 48 consecutive weeks.
Sponsors
The Second Affiliated Hospital of Zhejiang University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: Subjects who meet all of the following criteria may be enrolled in this trial: 1. Age > = 18 years old and =10 points and = 2.5 points (activity index score is the sum of the following scores): (1) The patient's skin assessment deteriorated compared with the previous month: 1.5 points; (2) Finger ulcer: 1.5 points; (3) mRSS >18: 1.5 points, or mRSS 1 mg/dl (not related to infectious diseases): 2.25 points; (6) Carbon monoxide diffusion capacity (DLCO) < 70% predicted value: 1.0 points. 6. Fully understand the content of the trial, be willing and able to comply with the requirements of the trial, and sign the informed consent form to participate in the trial.
Exclusion criteria
Exclusion criteria: Subjects are not allowed to enter this trial if they meet any of the following criteria: 1. Suffering from any rheumatic immune disease other than SSc, except for secondary Sjögren's syndrome; 2. Accompanied by severe gastrointestinal complications related to systemic sclerosis, such as pseudo-intestinal obstruction, malabsorption requiring parenteral nutrition, etc., or gastrointestinal diseases that, in the opinion of the investigator, may significantly affect the absorption of the study drug; 3. Those with a history of renal crisis with scleroderma within 6 months prior to randomization; 4. Previous diagnosis of moderate to severe pulmonary hypertension or systolic pulmonary artery pressure > 45 mmHg measured by echocardiography at screening; 5. Subjects with clinically significant chronic intermittent bleeding (such as active antral vasodilation, active peptic ulcer or duodenal ulcer) within 30 days prior to screening, or subjects at risk of bleeding; 6. Patients with severe cardiovascular (NYHA classification >=grade III., LVEF 120 beats/min, grade II and above atrioventricular block), lung (FVC 2.0x upper limit of normal (ULN); Creatinine (Cr) or urea (Urea) >2.0xULN; 10. Active hepatitis B (positive HBsAg test with HBV-DNA > 500 IU/ml or the lower limit of detection at the site [only if the lower limit at the site is higher than 500 IU/ml]) or active hepatitis C (positive for HCV antibodies and > HCV-RNAlower limit of detection by clinical trial institutions), HIV-positive or syphilis infected patients; 11. Use of a higher dose of glucocorticoids (> 10 mg/day equivalent dose of prednisone; or change in glucocorticoid dose within 4 weeks prior to randomization; or expected dose increase during the course of the study; 12. Use of high-dose immunosuppressants (azathioprine> 100 mg/d within 4 weeks prior to randomization; Methotrexate> 15 mg/week; mycophenolate mofetil > 2 g/d; Cyclosporine > 200 mg/day; Tacrolimus > 2 mg/d., or a change in immunosuppressant dose within 4 weeks prior to randomization, or a change in dose expected during the course of the study; 13. Those who have received the following treatments within the following limited time before randomization: (1) Those who cannot stop using biological immunosuppressants (such as tocilizumab and rituximab) from 3 months before randomization to the end of treatment; (2) Those who cannot stop using other immunosuppressants from 4 weeks before randomization to the end of treatment (such as cyclophosphamide and JAK inhibitors, except for low-dose azathioprine, methotrexate, mycophenolate mofetil, cyclosporine and tacrolimus); (3) 14 days before randomization (or 5 half-lives of the drug
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in the modified Rodnan Skin Score (mRSS) after 48 weeks of treatment. ; | — |
Secondary
| Measure | Time frame |
|---|---|
| Changes from baseline in mRSS at Weeks 4, 12, 24, and 36. ;Response assessment using the revised Combined Response Index for Systemic Sclerosis (CRISS-25) at Weeks 12, 24, and 48. ;Changes in Forced Vital Capacity (FVC), FVC % predicted, and Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) from baseline after 12, 24, and 48 weeks of treatment; ;Changes in Cochin Hand Function Score, Health Assessment Questionnaire Disability Index (HAQ-DI), and Raynaud’s Symptom Score from baseline after 4, 12, 24, 36, and 48 weeks of treatment.;Changes in serum IL-6, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) from baseline after 4, 12, 24, 36, and 48 weeks of treatment.;Changes in skin histopathology and immunohistochemistry results from baseline after 48 weeks.;Adverse events; | — |
Countries
China
Contacts
Public ContactJing Xue
The Second Affiliated Hospital of Zhejiang University School of Medicine
Outcome results
None listed