The overall study will include the following periods:~screening period (up to 4 weeks) - the evaluation of patient compliance with inclusion/exclusion criteria.~run-in period (29 weeks) - open-label administration of RPH-104 160 mg on Day 0, Day 7, Day 21 and then Q2W SC with gradual dose reduction with further complete withdrawal (if applicable) of the previous therapy with AOSD.~Baseline characteristics will be evaluated on Study Day 0. Assessment of efficacy (treatment response) and safety will be performed at Visit 2 (Day 7), Visit 3 (Day 21), Visit 4 (Day 35) and then every 4 weeks during the run-in period. A response to therapy during this period is the achievement of low activity/inactive disease including no exacerbations of AOSD.~The subjects who achieve and preserve low activity/inactive disease for at least 8 weeks under condition of receiving therapy with RPH-104 alone (i. e. previous therapy has been permanently discontinued) or combination of RPH-104 and glucocorticoids (GC) at stable dose achieved in reduction (not less than 50 % reduction vs baseline) for at least 4 weeks cannot be switched to the randomized withdrawal period.~• randomized withdrawal period (24 weeks) - blind SC administration of 160 mg of RPH-104 / equivalent volume of placebo Q2W depending on the distribution group in randomization; if the disease exacerbates during this period, a subject can be switched from placebo into a 53-week open-label therapy with RPH-104 (can be continued for 6 months in case of exacerbation as decided by the investigator).~Efficacy and safety assessment during the randomized withdrawal period will be performed every 4 weeks. During this period the investigational product/placebo will be administered to the subjects every 2 weeks - at visits to the study site - by the qualified medical staff (or a subject monitored by the staff) or at home by the subjects themselves. In case of self-administration of the investigational product/placebo by a subject during the randomized withdrawal period, additional conditions will be created to prevent from unblinding.~• safety follow-up period (8 weeks). The subjects who completed the randomized withdrawal period and the subjects who completed 53 weeks of resumed therapy (if applicable) and the subjects whose therapy was continued as decided by the investigator for 6 months after exacerbation in the randomized withdrawal period (for subjects from the investigational product group), or exacerbation during the resumed therapy - after the end of therapy will be switched into the safety follow-up period during which they will have to visit the study site for assessments in 2 and 8 weeks after the last dosing with the investigational products, thereafter their participation in the study will be considered completed.~The subjects who terminated therapy with RPH-104 early (for any reasons in any treatment period) will be prescribed with other products selected by the investigator and will have to make safety follow-up visits in 2 and 8 weeks after the last dosing with the investigational product.~Maximum possible duration of study per patient will be 144 weeks.~It is planned to randomize totally 56 patients with AOSD in the study. Given potential withdrawal at the screening and during the run-in period, the number of screened patients (who signed informed consent) will be up to 83.
The primary objective of the study is to evaluate the efficacy of RPH-104 when administered at a dose of 160 mg on Day 0, Day 7, Day 21 and then once every 2 weeks (Q2W) subcutaneous (SC) in patients with Adult Onset Still's Disease (AOSD). Furthermore, the study is scheduled to investigate pharmacokinetic (PK) and pharmacodynamic (PD) parameters of RPH-104.