Systemic Lupus Erthematosus
Conditions
Brief summary
This randomized, double-blind, parallel-group, noninferiority clinical trial will evaluate the efficacy and safety of ivarmacitinib compared with oral prednisone in participants with mild-to-moderate active systemic lupus erythematosus (SLE) without active major organ involvement. Approximately 294 participants will be randomized in a 1:1 ratio to receive either ivarmacitinib 8 mg once daily or oral prednisone starting at 30 mg/day with a prespecified tapering schedule, together with the corresponding matching placebo, for 24 weeks. The study will assess whether ivarmacitinib is noninferior to oral prednisone in achieving the primary efficacy outcome. The primary outcome is the proportion of participants achieving remission of arthritis and/or rash, as defined by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), at Week 12. Safety and secondary efficacy outcomes will be evaluated throughout the 24-week treatment period.
Interventions
Ivarmacitinib sulfate tablets, 8 mg orally once daily, plus matching prednisone acetate placebo tablets for 24 weeks. Stable background standard-of-care therapy is permitted.
Prednisone acetate tablets administered orally once daily, starting at 30 mg/day and tapered according to the protocol-specified schedule. Participants will also receive matching placebo tablets for ivarmacitinib once daily. Stable background standard-of-care therapy is permitted.
Sponsors
Chinese SLE Treatment And Research Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged ≥18 years. 2. Fulfill the 2012 SLICC classification criteria or the 2019 EULAR/ACR classification criteria for SLE. 3. Have a clinical SLEDAI-2K score ≥4 and a total SLEDAI-2K score ≤12. 4. Have active musculoskeletal and/or mucocutaneous manifestations at screening, as assessed by the SLEDAI-2K. 5. Be receiving a stable dose for at least 4 weeks before screening of oral glucocorticoids (prednisone ≤10 mg/day or equivalent), and/or an antimalarial agent, and/or one immunosuppressive agent.
Exclusion criteria
1. Active lupus nephritis at screening, defined as 24-hour urinary protein \>1 g. The 24-hour urinary protein test may be repeated once within 2 weeks; participants may be enrolled if the repeat result meets the eligibility criterion. 2. Active neuropsychiatric SLE (NPSLE) at screening, defined as new-onset seizure, psychosis, organic brain syndrome, visual disturbance, cranial neuropathy, lupus headache, or new-onset cerebrovascular accident. 3. Active hematologic involvement at screening, defined as any of the following: white blood cell count \<3 × 10\^9/L, platelet count \<100 × 10\^9/L, or hemolytic anemia. 4. Active gastrointestinal involvement at screening, defined as SLE-related acute pancreatitis or intestinal pseudo-obstruction. 5. Active cardiovascular or respiratory involvement at screening, defined as active diffuse alveolar hemorrhage, interstitial pulmonary fibrosis, pulmonary arterial hypertension, myocardial involvement, or valvular heart disease. 6. Active fibromyalgia at screening that, in the investigator's judgment, may interfere with assessment of SLE disease activity. 7. Treatment for or presence of an active systemic inflammatory disease other than SLE within 12 weeks before screening, including rheumatoid arthritis, juvenile chronic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, or psoriatic arthritis. Participants with secondary Sjögren's syndrome are not excluded. 8. Major surgery within 8 weeks before screening or anticipated need for major surgery during the study. 9. Any of the following within 12 weeks before screening: venous thromboembolism (deep vein thrombosis or pulmonary embolism), myocardial infarction, unstable ischemic heart disease, or stroke; or current New York Heart Association (NYHA) class III or IV heart failure. 10. History of recurrent venous thromboembolism, defined as ≥2 episodes of deep vein thrombosis and/or pulmonary embolism. 11. History or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematologic, neurologic, or neuropsychiatric disease, or any other serious and/or unstable medical condition that, in the investigator's judgment, may pose an unacceptable risk associated with administration of the investigational product or interfere with interpretation of study data. 12. History of a lymphoproliferative disorder; active primary or recurrent malignancy; or malignancy in remission for \<5 years before randomization. The following exceptions are permitted: 1. Cervical carcinoma in situ that has been surgically resected, with no evidence of recurrence or metastatic disease for at least 3 years. 2. Basal cell or squamous cell carcinoma of the skin that has been completely excised, with no evidence of recurrence for at least 3 years. 13. Clinically significant viral, bacterial, fungal, or parasitic infection within 4 weeks before randomization. 14. Symptomatic herpes simplex infection at the time of randomization. 15. Symptomatic herpes zoster infection within 12 weeks before randomization. 16. History of disseminated or complicated herpes zoster infection, including ophthalmic herpes zoster or central nervous system involvement. 17. Positive hepatitis B surface antigen (HBsAg), positive hepatitis C virus antibody, positive syphilis antibody, or human immunodeficiency virus (HIV) infection. 18. Active tuberculosis. 19. Receipt of any of the following treatments: 1. Intravenous, intramuscular, or intra-articular glucocorticoids within 6 weeks before screening; 2. Biologic therapies for immune-mediated diseases within the protocol-specified washout period before screening, including belimumab within 12 weeks, telitacicept within 12 weeks, and rituximab within 24 weeks; 3. Cyclophosphamide (or any other cytotoxic agent) within 12 weeks before screening; 4. Any cellular therapy within 24 weeks before screening. 20. Any prior treatment with a Janus kinase (JAK) inhibitor or tyrosine kinase 2 (TYK2) inhibitor. 21. Plasma exchange within 12 weeks before screening. 22. Receipt of a live vaccine within 12 weeks before randomization or anticipated need for a live vaccine during the study. 23. Pregnant or breastfeeding women. 24. Currently participating in, or having discontinued within 4 weeks before screening, any medical study involving an investigational product, a drug or device used for an unapproved indication, or any other medical research considered scientifically or medically incompatible with this study. 25. Unable to perform activities of daily living independently, for example, being bedridden. 26. Any other reason that, in the investigator's judgment, makes the participant unsuitable for participation in the clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Achieving Arthritis and/or Rash Remission as Defined by SLEDAI-2K | Week 12 | The SLEDAI-2K is a weighted index comprising 24 clinical and laboratory descriptors. The higher total score indicates greater disease activity. For this outcome, arthritis contributes 4 points and rash contributes 2 points when present; the corresponding item contributes 0 points when absent. For participants with arthritis only at baseline, response is defined as the absence of arthritis at Week 12. For participants with rash only at baseline, response is defined as the absence of rash at Week 12. For participants with both arthritis and rash at baseline, response is defined as the absence of arthritis, rash, or both at Week 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Achieving a BICLA Response | Week 12 | The BICLA response was defined as a reduction of all severe (BILAG-2004 A) or moderately severe (BILAG-2004 B) disease activity at baseline to lower levels (BILAG-2004 B, C, or D and C or D, respectively) and no worsening in other organ systems (with worsening defined as ≥1 new BILAG-2004 A item or ≥2 new BILAG-2004 B items); no worsening in disease activity, as determined by the SLEDAI-2K score (no increase from baseline) and by the PGA score (no increase of ≥0.3 points from baseline). |
| Proportion of Participants Achieving SRI-4 Response | Week 12 | The SRI-4 (SLE Responder Index-4) response was defined as a reduction of at least 4 points in SLEDAI score compared with the baseline level, no new British Isles Lupus Assessment Group (BILAG) A organ domain score or no more than one new BILAG B organ domain score, and no worsening in the Physician's Global Assessment (PGA) (\<0.3 points worsening from the baseline level). |
| Change From Baseline in SLEDAI-2K Total Score | Week 12 | SLEDAI stands for Systemic Lupus Erythematosus Disease Activity Index, with a score of 0-6 representing mild disease activity, 7-12 representing moderate disease activity, and \>12 representing severe disease activity. |
| Change From Baseline in Physician Global Assessment Score | Week 12 | Physician Global Assessment Score is used to assess the activity of systemic lupus erythematosus on a scale ranging from 0 to 3, where 0 indicates no disease activity and 3 indicates the most severe disease activity. |
Countries
China
Contacts
CONTACTMengtao Li
CONTACTLeyao Ma
Outcome results
None listed