Systemic Sclerosis, Diffuse
Conditions
Brief summary
The purpose of this study is to evaluate the safety, tolerability and efficacy of iguratimod in adult subjects with diffuse cutaneous systemic sclerosis.
Interventions
DRUGIguratimod
Iguratimod is an anti-rheumatic drug that approved for treating rheumatoid arthritis in East Asia. Recent data reveal its independent anti-fibrosis effect.
DRUGPlacebo
Placebo of Iguratimod
Sponsors
RenJi Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of systemic sclerosis (SSc), as classified using the 2013 American College of Rheumatology/ European Union League Against Rheumatism classification of SSc. * Diffuse Cutaneous Systemic Sclerosis (dcSSc) as defined by 2001 LeRoy and Medsger Disease duration ≤ 3 years (defined as time from the first non-Raynaud phenomenon manifestation). * Agree to use effective contraception during the study period (women of childbearing age). * Smokers agreed to quit smoking during the study. * Ability to provide informed consent.
Exclusion criteria
* The following drugs have been used within one month before screening: including TNF-α inhibitors (continuous use for more than 14 days), IL-6 inhibitors, abatacept (continuous use for more than 14 days), JAK inhibitors (continuous use for more than 14 days). * Used rituximab within 3 months before screening. * SSc with tumor. * People with various lung infections, asthma or other lung diseases such as bronchiectasis. * For patients with severe heart, liver, kidney and other important organ dysfunction, the evaluation criteria are as follows: ALT or AST is greater than 2 times the upper limit of normal, or total bilirubin rises twice; CPK\>400; Renal crisis, or hypertension of various causes (≥160/100mmHg) is not controlled; Creatinine clearance rate \<30ml/min; White blood cell count\<3×109/L; Hemoglobin \<80g/L; Platelet count\<60×109/L; Heart function level III-IV; PaO2\<50mmHg in resting state; FEV1/FVC\<0.7. * In the period of acute or chronic infection (not including finger ulcer combined infection). * A history of peptic ulcer or bleeding within 6 months before screening. * People with allergies or multiple drug allergies. * People with mental illness or other reasons who cannot cooperate with treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experience Grade 3 or Higher Adverse Events That Occur at or Before Week 24 | Week 24 | Primary outcome is met if any participants experience a grade 3 or higher event prior to Week 24. A grade 3 AE would constitute as severe. Grading was following using CTCAE v 4.03. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Grade 2 (Moderate) or Higher Adverse Events That Occur Throughout the Study | Week 12, 24, 36, and 48 | Grade 2 or higher assessed 12 weeks apart. Grade 2 AEs are determined as moderate. Grading was performed following CTCAE v 4.03 guidance. |
| Provisional American College of Rheumatology Combined Response Index (CRISS) Systemic Sclerosis | Week 12, 24, and 48 | CRISS components included the following domains: modified Rodnan skin score, forced vital capacity percent predicted, Physician Global Assessment, Patient Global Assessment, and Health Assessment Questionnaire Disability-Index. An algorithm determines the predicted probability of improvement from baseline by incorporating change in the mRSS, FVC percent predicted, Physician and Patient Global Assessments, and HAQ-DI. The outcome is a continuous variable between 0.0 and 1.0 (0 - 100%). A cut-off at 0.6 in the predicted probability of being improved has yielded the smallest misclassification error. Subjects are not considered improved if, between Visit 1 and 6, they develop new: 1) renal crisis; 2) decline in FVC% predicted by 15% (relative) from baseline and confirmed after 1 month; or 3) left ventricular failure (systolic ejection fraction \< 45%) or pulmonary artery hypertension. Higher CRISS scores indicates improvement. |
| Number of Grade 3 (Severe) or Higher Adverse Events That Occur Throughout the Study | Week 12, 24, 36, and 48 | Grade 3 or higher adverse events (AEs) assessed throughout the study ( 48 weeks). A grade 3 AE would constitute as severe. Grading was following using CTCAE v 4.03. |
| Change in Modified Rodnan Skin Score (mRSS) | Week 12, 24, 36, and 48 | The Modified Rodnan Skin Score (mRSS) is a measure of skin thickness. Skin thickness in 17 anatomic areas was rated on a 0-3 scale and scores are summed to obtain the mRSS (range from 0 - 51), with higher mRSS scores indicating worse disease activity |
| Change in Skin Thickness | Week 24, 48 | The skin thickness of fingers and palms would be measured by high frequency echo. detector. |
| Scleroderma Clinical Trials Consortium Damage Index | Week 24, 48 | A damage Index (DI) in systemic sclerosis, including musculoskeletal and skin, vascular, gastrointestinal, respiratory and cardiovascular damage caused by SSc. |
Outcome results
None listed