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

Ki nem vehet részt

• Planned surgery during the study
• Illicit drug or alcohol abuse
• Positive for human immunodeficiency virus antibody
• Treatment with investigational therapy within 28 days or 5 half-lives
• Previous and current treatment with anti-C1s antibody at any time
• Other complement inhibitors within 3 months
• Patients who receive any treatments which fall into the Prohibited Therapy Criteria
• 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
• 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
• 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
• 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
• 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
• History of anaphylaxis or hypersensitivity to a biologic agent
• Active infection requiring systemic antiviral, antibiotics or antifungal
• Clinical diagnosis of autoimmune diseases other than the target disease (except for Sjögren's syndrome in DM and IMNM)
• Positive for hepatitis B surface antigen
• Positive for hepatitis C virus antibody
• Evidence of current infection with tuberculosis
• History of cancer within 5 years
• Any serious medical condition or abnormality in clinical laboratory tests that precludes the patient's safe participation in and completion of the study
• Patients with an elevated alanine aminotransferase or aspartate aminotransferase > 1.5 × ULN in combination with an elevated total bilirubin > 1.5 × ULN
• 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
• Pregnant or breastfeeding, or intending to become pregnant
• Clinically significant ECG abnormalities

Egyéb feltételek

• Signed informed consent form
• Age ≥ 18 and ≤ 85 at the time of signing informed consent form with Karnofsky score ≥ 60 % at screening
• Ability to comply with the study protocol
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm
• APS cohort: Established primary APS defined by the following criteria (at least one of the laboratory criteria and one of the clinical criteria must be met):; Laboratory criteria (aPL profile); Persistently positive LA test; Persistently positive aCL IgG isotype; Persistently positive aβ2GPI IgG isotype; Clinical criteria; Livedoid vasculopathy and presence of skin ulcer; Acute/chronic aPL nephropathy
• BP cohort:
• Predominant cutaneous lesions 2) Diagnosis with BP with following assessments positive:
• Positive direct immunofluorescence, and either
• Positive indirect immunofluorescence, or
• Positive serology on ELISA for BP180 autoantibody 3) BPDAI score >= 20 4) Weekly average of daily Peak Pruritus NRS >=4 5) Accept to take photograph of bullous lesions; BS cohort:; Diagnosed with BS; Oral ulcers that occurred at least 3 times in the previous 12 month period; Have at least 2 oral ulcers over the 4 weeks prior to screening; Have at least 2 oral ulcers at Week 0; Have prior treatment with at least 1 non-biologic BS therapy; Patients who need systemic therapy as whose oral or mucocutaneous ulcers cannot be adequately controlled by topical therapy; DM cohort:; Diagnosed with definite or probable inflammatory myopathies and categorized as DM; Patients with inadequate response to corticosteroids and/or immune-suppressants or intolerance to DM therapies; MMT-8 score < 142, with at least one abnormality in the following Core Set Measures:; PtGA-VAS >= 2 cm; PhGA-VAS >= 2 cm; Global extra-muscular activity >= 2 cm; At least one muscle enzyme > 1.5 times ULN; HAQ >= 0.25; Moderate to severe DM defined as CDASI activity score > 14; IMNM cohort:; Clinically Diagnosed with IMNM as anti-HMGCR myopathy or anti-SRP myopathy; CK > 1,000 U/L; Patients who have an inadequate response to corticosteroids and/or immunesuppressants or intolerance to IMNM therapies; MMT-8 score < 142; ITP cohort:; Confirmed diagnosis of persistent/chronic ITP based on the following criteria:; ITP defined per the current guidelines; Platelet count <= 30 × 10\^9/L on 2 consecutive occasions; Lack of an sustained adequate platelet count response to a thrombopoietin receptor agonist and at least one other ITP treatment or a second TPO-RA; A history of response with an platelet counts increase more than 20 × 10\^9/L from baseline by at least one prior line of therapy