Phase 1b Trial of RAY121 in Immunological Diseases (RAINBOW Trial)

Exclusion Criteria

• •1. History of anaphylaxis or hypersensitivity to a biologic agent
• •2. Active infection requiring systemic antiviral, antibiotics or antifungal
• •3. Planned surgery during the study
• •4. Pregnant or breastfeeding, or intending to become pregnant
• •5. Any serious medical condition or abnormality in clinical laboratory tests that precludes the patient's safe participation in and completion of the study
• •6. Clinically significant ECG abnormalities
• •7. Illicit drug or alcohol abuse
• •8. Clinical diagnosis of autoimmune diseases other than the target disease (except for Sjögren's syndrome in DM and IMNM)
• •9. Positive for hepatitis B surface antigen
• •10. Positive for hepatitis C virus antibody
• •11. Positive for human immunodeficiency virus antibody
• •12. Evidence of current infection with tuberculosis
• •13. History of cancer within 5 years
• •14. Treatment with investigational therapy within 28 days or 5 half-lives
• •15. Previous and current treatment with anti-C1s antibody at any time
• •16. Other complement inhibitors within 3 months
• •17. Patients who receive any treatments which fall into the Prohibited Therapy Criteria
• •18. Patients with an elevated alanine aminotransferase or aspartate aminotransferase \> 1.5 × ULN in combination with an elevated total bilirubin \> 1.5 × ULN
• •19. APS cohort:
• •* 1\) APS associated with other systemic autoimmune disease
• •* 2\) Acute thrombosis (arterial or venous acute thrombosis diagnosis) within 30 days before screening
• •* 3\) Patients with thrombotic APS without any anticoagulation treatment
• •* 4\) Treatment with prohibited medications
• •20. BP cohort:
• •* 1\) Initiation of treatment with or increase in the dose of systemic or topical corticosteroid within 2 weeks
• •* 2\) Current treatment with a drug that may cause or exacerbate BP unless the dose has been stable
• •* 3\) Initiation of treatment with topical calcineurin inhibitor, or topical phosphodiesterase (PDE) 4 inhibitor within 7 days
• •* 4\) Treatment with prohibited medications
• •21. BS cohort:
• •* 1\) BS-related active major organ involvement-ocular lesions requiring immunosuppressive therapy, pulmonary (e.g., pulmonary artery aneurysm), vascular (e.g., thrombophlebitis), gastrointestinal (e.g., ulcers along the gastrointestinal tract), and central nervous systems (e.g., meningoencephalitis) manifestations
• •* 2\) History of venous or arterial thrombosis within 1 year
• •* 3\) Treatment with prohibited medications
• •22. DM cohort:
• •* 1\) PhGA-VAS improvement \>= 3, or clinically relevant improvement between screening and baseline
• •* 2\) Overlap myositis (except for overlap with Sjögren's syndrome), connective tissue disease associated DM, inclusion body myositis, polymyositis, IMNM, juvenile DM or drug-induced myopathy
• •* 3\) Cancer-associated myositis
• •* 4\) Significant muscle damage
• •* 5\) Past history of severe Interstitial lung disease flare, severe non-infectious lung inflammation which required active intervention, or multiple episodes of lung disease
• •* 6\) Severe respiratory muscle weakness
• •* 7\) Severe bulbar palsy
• •* 8\) Treatment with prohibited medications
• •23. IMNM cohort:
• •* 1\) PhGA-VAS improvement \>= 3, or clinically relevant improvement between screening and baseline
• •* 2\) Overlap myositis (except for overlap with Sjögren's syndrome), connective tissue disease associated DM, inclusion body myositis, polymyositis, juvenile DM or druginduced myopathy
• •* 3\) Cancer-associated myositis
• •* 4\) Significant muscle damage
• •* 5\) Past history of severe Interstitial lung disease (ILD) flare, severe non-infectious lung inflammation which required active intervention, or multiple episodes of lung disease
• •* 6\) Severe respiratory muscle weakness
• •* 7\) Severe bulbar palsy
• •* 8\) Treatment with prohibited medications
• •24. ITP cohort:
• •* 1\) Secondary ITP
• •* 2\) Clinical diagnosis or history of Myelodysplastic Syndrome or autoimmune hemolytic anemia
• •* 3\) History of venous or arterial thrombosis within 12 months
• •* 4\) Patients who experienced major bleeding within 4 weeks
• •* 5\) Treatment with prohibited medications
• •* 6\) Any laboratory test results meet either of the following criteria at screening:
• •* Hemoglobin \<10 g/dL
• •* Thyroid-stimulating hormone \>= 10 μIU/mL