Treatment of Active Axial Spondyloarthritis by Recombinant Human Tumor Necrosis Factor-α Receptor Ⅱ IgG Fc Fusion Protein Injection: a Randomized, Double-blind, Multicentral Clinical Trial to Investigate the Efficacy and Safety of Yisaipu®

This randomised controlled trial enrolled adult patients aged 18 years or older diagnosed with non-radiographic axial spondyloarthritis at 3 centres in China. Patients had to fulfil ASAS axial spondyloarthritis criteria but could not fulfil the modified New York radiologic criterion for ankylosing spondylitis,and had to have objective evidence of active inflammation or chronic structral change，such as bone erosion or fat metaplasia in the sacroiliac joints on MRI at screening. Active disease activity was defined as a disease activity score in ASDAS-CRP ≥2.1,or Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] ≥4 on a numerical rating scale of 0-10, and an inadequate response to more than one non-steroidal anti-inflammatory drugs (NSAIDs) for 4 weeks at least, intolerance to NSAIDs, or contraindication for NSAIDs. No change in NSAIDs dose was required from 2 weeks before screening to the end of the study. Dose stability or discontinuation was required for 4 weeks before baseline for concomitant DMARDs or corticosteroids (prednisone or equivalent at a dose of less than 10 mg/day). Chinese herbal medicine, physical therapy, or live (attenuated) vaccine, or intravenous immunoglobulin IgG, was required for discontinuation and wash period for at least 4 weeks. Patients were excluded if they had previously taken or were taking biologic treatment, any biologic Dmards such as IL-6 or CD-20 inhibitors. Patients with latent tuberculosis infection were included only when local guidelines were followed for prophylactic treatment and if treatment was initiated before Yisaipu.

All patients provided written informed consent, and the study protocol was approved by an institutional review board or independent ethics committee at each study site. The study was conducted in accordance with applicable regulations and the ethical principles of Good Clinical Practice as defined by the International Conference on Harmonisation (ICH) and the Declaration of Helsinki.

A randomized envelope was used to enrol all patients at the baseline visit and to randomly assign qualifying patients in a 1:1:1 ratio to receive either blinded Yisaipu 50 mg subcutaneously every week or 25 mg subcutaneously every week or matching placebo at week 24. All study personnel, including the sponsor (with the exception of the Sanshengguojian drug supply management team), investigator, and study site personnel, and the patient remained blinded to treatment throughout the double-blinded period from week 24 through week 72 of the study. Investigational products were provided to maintain blinding.

In the initial open-label period, enrolled patients were given subcutaneous injections of 50 mg Yisaipu every week for 36 weeks. Participants were given the dose of NSAIDs they had been receiving at screening; a dose decrease or discontinuation was allowed when the patients were intolerance to NSAIDs, or contraindication for NSAIDs. Patients who achieved clinical remission, defined as achieving ASDAS inactive or moderate disease (ASDAS score <2.1) at weeks 24, were randomly assigned to receive either blinded 50mg Yisaipu (continuation arm), 25mg Yisaipu(reduction arm) or matching placebo (withdrawal arm) for 48 weeks during the double-blind period, for a total of 72 weeks of treatment.

During the double-blind period, patients who experienced a flare (defined as an increase in BASDAI ≥2 points compare to the BASDAI score when randomization) were allocate to termination of this trial.