Rheumatoid Arthritis or Systemic Lupus Erythematosus
Conditions
Interventions
intervention group:Surovatamig (AZD0486)
Sponsors
Peking University First Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1. Participant must be 18 (or the legal age of consent in the jurisdiction in which the study is taking place) to 65 years of age, inclusive, at the time of signing the informed consent. 2. Participants with RA, only:Diagnosis of RA as defined by the 2010 EULAR/ACR classification criteria (Aletaha et al 2010); 3. Participants with RA, only: Positive for >= 1 disease-specific autoantibody performed by the central laboratory at screening. (a) RF (b) ACPA; 4. Participants with RA, only: Moderate or severe disease activity defined as >= 4 tender joints and >= 4 swollen joints (not including distal interphalangeal joints); 5. Participants with RA, only: Intolerance to or inadequate response following approximately 3 month’s treatment or longer to >=2 b/tsDMARDs (with different mechanisms of action) after failing csDMARD therapy (unless csDMARD therapy is contraindicated). There is no minimum duration for taking a treatment in cases of intolerance. 6. Participants with RA, only: Background standard of care is not a requirement for participation, however, the following therapies are permitted and may be continued during the study (alone or in combination): (a) Oral prednisone (or equivalent). Dose must be stable and = 2 weeks prior to Day 1. (b) Oral anti-malarial (e.g. hydroxychloroquine = 4 weeks prior to Day 1. (c) Treatment with one of the following csDMARDs for >= 3 months and at a stable dose for >= 4 weeks prior to Day 1. (i) Methotrexate = 1 disease-specific autoantibody performed by the central laboratory at screening. If autoantibodies are negative at screening, documented history of test results may be used. (a) ANA immunofluorescent assay test (titer >= 1:80) (a) Anti-dsDNA (b) Anti-Sm. 9. Participants with SLE, only: Moderate or severe disease activity defined as clinical SLEDAI-2K > 4; 10. Participants with SLE, only: Intolerance to or inadequate response following approximately 3 months treatment or longer >= 3 SoC (includes: corticosteroids, anti-malarial drugs, calcineurin inhibitor, methotrexate, azathioprine, leflunomide, mycophenolic acid or its derivatives, cyclophosphamide, belimumab, anifrolumab, or B-cell depleting monoclonal antibodies). There is no minimum duration for taking a treatment in cases of intolerance. (a) USA-specific criterion: Of the 3 or more SoC medications that resulted in intolerance or inadequate response, at least one must be either a biologic SoC agent or cyclophosphamide. 11. Participants with SLE, only: Background standard of care is not a requirement for participation, however, the following therapies are permitted and may be continued during the study (alone or in combination): (a) Oral prednisone (or equivalent. Dose must be stable and = 2 weeks prior to Day 1. (b) Oral anti-malarial (eg, hydroxychloroquine = 4 weeks prior to Day 1. (c) Treatment with one of the following immunosuppressive treatments. for >= 3 months and at a stable dose for >= 4 weeks prior to Day 1. (i) Methotrexate <= 25 mg/week, without change of route of administration for
Exclusion criteria
Exclusion criteria: 1. Any complications of disease under study that are judged by the Investigator to be life or organ threatening or to require treatments which are not permitted in the protocol, including but not limited to: (a) Active severe SLE-driven renal disease. (b) Severe lung or cardiac involvement. (c) History of, or current diagnosis of, catastrophic or severe APS (eg, diagnosis of an arterial or central/pulmonary venous clot) within 1 year prior to signing the ICF. Participants with clinically evident APS which is adequately controlled by anticoagulants or aspirin for at least 12 weeks can be recruited into the study. (d) Rapidly progressive and/or severe ILD or ILD that requires oxygen supplementation/therapy (of any type). (e) Felty’s syndrome; 2. History of HLH/MAS. 3. For RA participants, only: Juvenile idiopathic arthritis or idiopathic arthritis diagnosed before the age of 16. 4. For RA participants, only: Axial spondylarthritis or any other disease associated with inflammatory arthritis; 5. For SLE participants, only: History of active, severe or unstable neuropsychiatric SLE including, but not limited to: aseptic meningitis; cerebral vasculitis; myelopathy; demyelination syndromes (ascending, transverse, acute inflammatory demyelinating polyradiculopathy); acute confusional state; impaired level of consciousness; psychosis; acute stroke or stroke syndrome; cranial neuropathy; status epilepticus; cerebral ataxia, and mononeuritis multiplex. 6. Other active or prior documented severe, complex, autoimmune or inflammatory disorders. Exceptions to this exclusion criteria include: (a) Vitiligo or alopecia (b) Hypothyroidism stable on hormone replacement (c) Controlled type I diabetes mellitus on insulin (d) Any chronic skin condition that does not require systemic therapy (e) Celiac disease, controlled by diet alone (f) Sjögren’s syndrome; 7. Significant CNS co-morbidity (eg, Parkinson’s, stroke, CNS vasculitis, severe brain injury, dementia, neurodegenerative diseases, cerebellar disease, epilepsy/seizure disorders, PML, severe uncontrolled mental illness, psychosis, CNS involvement of autoimmune diseases). 8. History of cancer: (a) Participant who has had basal cell carcinoma, localised squamous cell carcinoma of the skin or in situ carcinoma of the cervix is eligible to participate in the study provided that curative therapy was completed at least 12 months prior to screening. (b) Participant who has a current or previous diagnosis of any malignancy other than those described in (a) should be excluded. 9. Recent history (within 6 months) or current diagnosis of ongoing clinically significant cardiovascular disease (eg, myocardial infarction, unstable angina, cardiomyopathy, valvular disorder, arrhythmias requiring treatment [atrial fibrillation with controlled HR < 100 bpm can be included] or congestive heart failure). 10. Family history of long QT syndrome. 11. History of chronic significant respiratory disease (eg, severe or inadequately controlled chronic obstructive pulmonary disease or asthma). 12. Major surgery within 3 months prior to signing the ICF. 13. Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection. 14. Any clinical suspicion or diagnosis of active infection at screening. 15. Opportunistic infection that meets criteria to be an SAE within 3 years. 16. Clinically significant chronic infection (for example osteomyelitis, bronchiect
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence and severity of DLTs;Incidence and severity of AE,TEAEs, SAE and AESIs;Clinically significant alterations in vital signs, clinical laboratory and ECG; | — |
Secondary
| Measure | Time frame |
|---|---|
| Absolute counts at Day 180 in blood CD20+ B cells;Serum PK parameters of surovatamig, including but not limited to Cmax, AUC0-last, AUC0-inf (Part 1 only), AUCtau (Parts 2 and 3 only), as data allow.;Count of blood CD8+ and CD4+ T cell and change from baseline ? Count and percentage of activated CD8+ and CD4+ cells, and change from baseline;Treatment-emergent ADA incidence to surovatamig measured in serum will be summarized; | — |
Countries
China
Contacts
Public ContactZhang Zhuoli
Peking University First Hospital
Outcome results
None listed