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Introduction Systemic sclerosis (SSc), a chronic inflammatory autoimmune disease, causes highly variable but progressive tissue and vascular fibrosis and loss of function of the skin and internal organs. Type I interferon (Type I IFN) has been strongly linked to the underlying disease mechanisms of SSc. Anifrolumab, a Type I IFN receptor inhibitor, is currently approved for patients with moderate to severe SLE and is undergoing evaluation in an international Phase III trial (DAISY). DAISY, adopts a combined outcome measure as primary endpoint to include, mRSS, FVC, HAQ-DI, patient and physician global assessment of disease activity (CRISS25 NCT05925803). Here, we aimed to assess the safety and tolerability of anifrolumab on patients that would not meet DAISY inclusion criteria and to inform the feasibility of adopting hand function as clinical endpoint.Material and Methods REASCENT is a single arm, open label proof of principle trial to evaluate the safety and tolerability of 300 mg anifrolumab (52-week treatment period via monthly infusion) in patients with SSc. Utilising the TwiCs design, patients will undergo pre-screening and random selection within the observational cohort study; STRIKE (IRAS ID: 178638). Eligible patients aged 18-70 years of age will be assessed for key inclusion criteria including diagnosis of SSc as per 2013 ACR/EULAR criteria, Cochin Hand Function Score over patient acceptable threshold (>25) at baseline and either mRSS <10 or disease duration >7 years. Patients who meet the pre-screening criteria will be randomly allocated (1:1) to remain on standard of care or be approached and consented to be treated with IV anifrolumab 300mg/month.Results Both safety and clinical parameters will be evaluated as feasibility outcomes within this trial at 24 and 52 weeks. The primary objective, safety and tolerability, will be described through the proportion of adverse events. Secondary objectives include the effect of anifrolumab on hand function, inflammatory markers and IFN chemokine score, patient reported disability and vascular and articular manifestations; change in nailfold videocapillaroscopy pattern, and imaging features of skin and joints including ultrasound. Exploratory objectives include change in Optical Coherence Tomography features.Conclusions Primarily, the data from this Phase II study, will complement the evidence from the Phase 3 trial of anifrolumab in SSc. Further, we will appraise the feasibility of utilising the TwiCs design as a pragmatic option for evaluation of novel treatments.Abstract P.260 Figure 1