REASCENT trial: a proof of principle trial to treat active systemic sclerosis via interferon inhibition

INTERVENTION: This is a single‐arm, open‐label, proof‐of‐principle trial to evaluate the safety and tolerability of an intravenous (IV) treatment regimen of anifrolumab 300 mg in patients with active systemic sclerosis (SSc) while receiving standard of care (SOC) treatment. Participants enrolled in REASCENT will receive a fixed intravenous dose of anifrolumab 300 mg every 4 weeks (Q4W) for a total of 13 doses (Week 0 to Week 48). CONDITION: Systemic sclerosis ; Skin and Connective Tissue Diseases ; Scleroderma PRIMARY OUTCOME: Safety and tolerability of anifrolumab with endpoints including adverse events (AEs) (including adverse events of special interest [AESIs]), assessments including but not limited to vital signs, physical examination, 12‐lead electrocardiograms, clinical laboratory tests (haematology, clinical chemistry, urinalysis) measured using NHS laboratory and/or clinical evaluation from the point of participant consent throughout the treatment and follow‐up period SECONDARY OUTCOME: 1. Hand function is measured using the Cochin Hand Function Scale (CHFS) at baseline, Week 24, and Week 52 ; 2. Type I interferon (IFN) inducible chemokine activity is measured using serum IFN‐inducible chemokine score at baseline, Week 24, and Week 52 ; 3. Inflammatory activity is measured using NHS laboratory evaluation of IFN inducible chemokine score, troponin, CRP, NT‐proBNP, complement (C3, C4) at baseline, Week 24, and Week 52 ; 4. Patient‐reported disability is measured using the HAQ‐DI questionnaire at baseline, Week 24, and Week 52 ; 5. Patient‐reported disability is measured using the EULAR ScleroID questionnaire at baseline, Week 24, and Week 52 ; 6. Pain intensity is measured using a visual analogue scale (VAS) at baseline, Week 24, and Week 52 ; 7. Raynaud’s phenomenon severity is measured using the Raynaud Condition Score (RCS) at baseline, Week 24, and Week 52 ; 8. Digital ulcer incidence is measured using the proportion of patients with new digital ulcers at baseline, Week 24, and Week 52 ; 9. Digital ulcer activity is measured using a patient‐reported visual analogue scale (VAS) at baseline, Week 24, and Week 52 ; 10. Microvascular abnormalities are measured using nailfold videocapillaroscopy at baseline, Week 24, and Week 52 ; 11. Synovitis is measured using musculoskeletal ultrasound at baseline, Week 24, and Week 52 ; 12. Joint stiffness is measured using shear wave elastography at baseline, Week 24, and Week 52 ; 13. Patient‐reported joint disease activity is measured using a visual analogue scale (VAS) at baseline, Week 24, and Week 52 INCLUSION CRITERIA: 1. Provision of informed consent prior to any study specific procedures (signing informed consent form [ICF]) 2. Completion of all screening procedures within 30 days of confirmation of eligibility 3. Adult male or female patient aged 18 to 70 years at the time of screening 4. Weight >40 kg at screening 5. Diagnosis of SSc according to the ACR 2013 classification criteria (van den Hoogen et al. 2013) 6. Patient‐reported hand‐disability according to CHFS>25 at baseline 7. Modified Rodnan Skin score (mRSS) either: <10 or any mRSS if disease duration >7 years 8. Complete COVID‐19 vaccination record according to national guidelines. Negative PCR or antigen test result at screening (according to local guidelines) and no known or suspected COVID‐19 infection or exposure between screening and randomization visits. There must be a minimum of 2 weeks between screening and randomization visits. If suspected infection or known/suspected exposure: Negative