a study of gnc-038 tetra-specific antibody injection in patients with rheumatoid arthritis

Conditions: Rheumatoid Arthritis

Summary: this study is a randomized controlled phase i clinical study with safety, efficacy, and pharmacokinetic/pharmacodynamic characteristics in patients with rheumatoid arthritis.

this study is divided into a phase ia study and a phase ib study. the phase ib study has a randomized controlled design with a placebo control group. the phase ia study has a single-arm design, and the phase ib study will be carried out on the basis of the phase ia study.

Eligibility criteria:
inclusion criteria: 1. subjects can understand the informed consent form, voluntarily participate in and sign the informed consent form; 2. no gender limit; 3. age: ≥18 years old and ≤75 years old; 4. life expectancy greater than 6 months; 5. patients diagnosed with rheumatoid arthritis according to 1987 or 2010 american college of rheumatology (acr)/european league against rheumatism (eular) classification criteria; 6. patients were moderately to severely active ra at the time of screening; 7. a stable standard-of-care regimen was maintained for at least 30 days before the first dose; 8. previous treatment with antirheumatic drugs other than mtx: leflunomide should be discontinued at least 8 weeks before the start of study treatment or cholestyramine should be used for 14 days; 9. erythrocyte sedimentation rate (esr) \> 28mm/hr or c-reactive protein (crp) \> 10mg/l; 10. positive rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies; 11. there were cd19+ b cells in the peripheral blood of the patient; 12. diagnosis of rheumatoid arthritis (ra) more than 6 months; 13. the organ function level before the first administration met the requirements; 14. fertile female subjects or male subjects with fertile partners must use highly effective contraception from 7 days before the first dose until 24 weeks after the termination of treatment and should commit not to donate eggs (eggs, oocytes)/sperm for assisted reproduction for 1 year after the last study treatment. female subjects of childbearing potential must have a negative serum/urine pregnancy test within 7 days before the first dose; 15. participants were able and willing to comply with protocol-specified visits, treatment plans, laboratory tests, and other study-related procedures. exclusion criteria: 1. confirmed diagnosis of another autoimmune rheumatic disease; 2. b cell-targeted therapy agents administered within 6 months before gnc-038 treatment; 3. received car-t therapy within 6 months before gnc-038 treatment; 4. use of anti-tnf drugs within 8 weeks before administration; 5. use of any jak inhibitor within 2 weeks before dosing; 6. antimalarial drugs, sulfasalazine, penicillamine, etc. were used within 4 weeks before the drug administration; 7. use of phytochemicals within 4 weeks before administration; 8. the use of other biological agents or other non-b cell depleting clinical investigational drugs before drug administration did not exceed 5 half-lives; 9. received an intra-articular injection within 4 weeks before study entry; 10. receipt of any investigational drug within 28 days before dose or within 5 half-lives of the investigational drug; 11. acr functional class iv or bedridden/wheelchair-bound; 12. history of major organ transplantation or hematopoietic stem cell/bone marrow transplantation; 13. presence of: 1) active hepatitis b at screening; 2) hepatitis c or hiv infection; 3) syphilis infection; 14. a history of any cardiovascular disease described in the protocol within 6 months before screening; 15. poorly controlled hypertension (systolic blood pressure \&gt; 160 mmhg or diastolic blood pressure \&gt; 100 mmhg); 16. prolonged qt interval at rest (qtcf \> 450 msec in men or \> 470 msec in women); 17. a history of ≥ grade 2 bleeding within 30 days before screening or the need for long-term continuous anticoagulant therapy; 18. patients with a history of allergy to recombinant humanized antibodies or to any of the excipients of gnc-038; 19. women who are pregnant or breastfeeding; 20. having a history or evidence of suicidal thoughts within 6 months before signing icf, which is considered by the researcher to be a significant risk of suicide; 21. diagnosed with malignant tumor within 5 years before signing icf; 22. other situations of poor compliance, unwillingness or inability to comply with the study protocol as judged by the investigator; 23. history of splenectomy; 24. investigators considered a history of alcohol or drug abuse in the 12 months before screening; 25. any active infection requiring systemic antibiotic treatment within 2 weeks before or during screening; 26. a history of severe and/or disseminated viral infection; 27. active m. tuberculosis infection may be present.