Efficacy and Safety of IBI303 in Adult Patients With Active Ankylosing Spondylitis

Adults patients with active ankylosing spondylitis (AS) were randomized in a 1:1 ratio to receive treatment with adalimumab 40 mg every other week (eow) or IBI303, given subcutaneously (SC), in the 24-week double-blind (DB) phase. Randomized participants received one SC injection of the appropriate DB study medication (adalimumab 40 mg or IBI303) at Week 0 and then eow until Week 22. A follow-up visit occurred 70 days(Week 32) after the last dose of study drug to obtain information on any ongoing or new adverse events (AEs).

Inclusion criteria

• Between 18 and 65 years of age
• Fulfilled modified New York Criteria for AS, had active disease（as defined by≥2 of the following: Bath AS Disease Activity Index(BASDAI) ≥4(10cm VAS); total back pain≥40(100mm VAS) and ≥1 hour of morning stiffness）
• No response, or inadequate response, or intolerant to≥1 NSAID at least 4 weeks
• Participants who are regularly taking DMARDs(SSZ≤3g/day，MTX≤15mg/week) as part of their AS therapy are required to be on a stable dose ≥28 days prior to Baseline, and are required to be on a stable DMARDs dose and to accept oral folic acid therapy(≥5mg/week) during the study period；
• Participants who are regularly taking NSAIDs as part of their AS therapy are required to be on a stable dose ≥14 days prior to Baseline, and are required to be on a stable dose during the study period；
• Glucocorticoid must be withdrawn for at least 4 weeks prior to Baseline, and were not allowed during the study period.
• Total duration of prior physical therapy should be at least 2 weeks
• Traditional Chinese medicines to AS must be withdrawn for at least 28 days prior to Baseline, and were not allowed during the study period.
• Biological agents must be withdrawn: etanercept and anakinra(IL-1 receptor antagonist) for at least 4 weeks prior to administration; tocilizumab(IL-6 monoclonal antibody) for at least 12 weeks prior to administration; other biological agents for 12 weeks or 5 half-lives(whichever is longer) prior to administration
• Male subjects' partner, or female subjects should be willing to use adequate contraception from admission to clinical research center until 5 months post dosing；
• To fully understanding the purpose of the study, to understand the pharmacological action of the study drugs and the possible adverse reactions; participants who are voluntary to sign the informed consent according to the Declaration of Helsinki
• Blood routine examination: hemoglobin ≥90g/L, WBC count ≥3.5×109/L, PLT count ≥100×109/L; liver function examination: total bilirubin(TBIL), direct bilirubin(DBIL), aspartate transaminase(AST) or alanine aminotransferase (ALT) <1.5×ULN; kidney function examination：creatinine(Cr) ≤ULM, usea nitrogen(BUN) ≤1.25×ULN

Exclusion criteria

• No response to prior tumor necrosis factor-α inhibitors treatment
• Use of DMARD(except for sulfasalazine or methotrexate) within 4 weeks prior to Baseline
• Use of opioid analgesics(such as methadone, morphine) within 4 weeks prior to Baseline
• X-ray suggests total spinal ankylosis, or sacroiliac joint fusion
• Patients with moderate to severe congestive heart failure（NYHA ）
• Has received intra-articular joint injection(s), spinal or paraspinal injection(s) with corticosteroids within 28 days prior to Baseline
• Has undergone spinal surgery or joint surgery within 2 months prior to the administration of the study drugs
• Patients with other rheumatic diseases or immunodeficiency, including inflammatory bowel disease(IBD), psoriasis, active uveitis
• Recent active or chronic infection requiring anti-infective therapy, such as M.tuberculosis, Listeriosis, Histophasmosis
• Tuberculosis(TB) history, or a positive T-SPOT test, or chest radiograph suggests active TB
• Positive serology for human immunodeficiency virus(HIV) antibody
• Positive serology for hepatitis C virus antibody
• Active or chronic HBV infection, such as positive hepatitis B virus surface antigen
• Malignancy history ≤5 years（except for successfully treated cutaneous squamous cell carcinoma, or basal cell carcinoma, or localized cervical carcinoma in situ, or breast ductal carcinoma in situ）
• History of relevant allergy/hypersensitivity (including allergy to the study medications or its excipients)
• Prior or recent central nervous system demyelinating disease or multiple sclerosis
• Use of live vaccines within 3 months prior to Baseline
• Pregnant or breastfeeding women
• Suspected or confirmed drug/alcohol use
• Participation in another interventional trial within 3 months prior to administration
• Subjects with serious psychiatric or nervous system diseases, or patients who have difficulty in informing consent or AE presentation, or illiterate patients
• Subjects who are unable to complete the study, or who may not be able to comply with the requirement of the study, judged by the investigators