This is a phase II, single-centre, open-label pilot study evaluating the safety and tolerability of anifrolumab in adult patients with primary antiphospholipid syndrome (APS). Approximately 20 participants will receive 120 mg subcutaneous anifrolumab once weekly for up to 52 weeks in addition to their standard of care treatment.
The primary objective is to assess the incidence of adverse events during treatment. Secondary and exploratory objectives include evaluation of immunological parameters, thromboinflammatory markers, and patient-reported outcomes. Participants will be followed for an additional 12-week safety follow-up period after completion of treatment.
Provision of written informed consent (ICF) prior to any study-specific procedures.
Females/males aged 18 to 70 years at Screening (at the time of ICF signing).
Weight ≥40.0 kg at Screening.
Classified as having primary APS as per the 2023 ACR/EULAR APS classification criteria, i.e. fulfilling at least one documented clinical criterion [ie., macrovascular (venous thromboembolism and/or arterial thrombosis), established microvascular (livedoid vasculopathy, aPL nephropathy, pulmonary haemorrhage or myocardial disease), cardiac valve (valve thickening or valve vegetation) and/or haematology (thrombocytopenia)] and at least one laboratory criterion and scoring at least three points in each of the clinical and laboratory domains.
Any condition that, in the opinion of the Investigator, would interfere with the efficacy or safety evaluation of the study intervention or put the participant at safety risk.
Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site).
Current participation in another clinical study with an IP.
Lactating or pregnant females or females who intend to become pregnant anytime from initiation of Screening through the Safety Follow-up Period (12 weeks following last dose of IP).
Single group
Anifrolumab
DrugAnifrolumab 120 mg administered subcutaneously once weekly for up to 52 weeks in addition to standard of care treatment.
Safety and tolerability of anifrolumab
Incidence of adverse events (AEs) including adverse events of special interest \[AESIs; i.e., opportunistic infections, serious non-opportunistic infections, herpes zoster, influenza, malignancies, anaphylaxis\]
Pharmacodynamics (PD) of anifrolumab
Change from baseline (neutralization rate) in type I IFN signature, as assessed by a validated 4-gene panel at weeks 24 and 52
Effect of anifrolumab on the patient's immunological profile
Change from baseline in aCL and aβ2GPI IgG antibody titres at weeks 12, 24 and 52
Effect of anifrolumab on the patients' immunological profile
Change from baseline in lupus anticoagulant (LA) status at weeks 24 and 52
Effect of anifrolumab on the patient's immunological profile
Change from baseline in complement C3 and C4 levels at weeks 12, 24 and 52
Evaluate the efficacy of anifrolumab in the prevention of recurrent thrombotic APS events
Rate of recurrent venous or arterial thrombotic events in patients with thrombotic APS by week 52
Evaluate the efficacy of anifrolumab in livedoid vasculopathy/skin ulcers
Proportion of patients with livedoid vasculopathy/skin ulcers at baseline achieving complete, partial or no response (as defined in the protocol) by week 52
Evaluate the efficacy of anifrolumab in APS nephropathy features
Proportion of patients with APS nephropathy at baseline achieving complete, partial or no response (as defined in the protocol) by week 52
The efficacy of anifrolumab in pulmonary haemorrhage
Proportion of patients with pulmonary haemorrhage at baseline achieving complete, partial or no response (as defined in the protocol) by week 52
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National and Kapodistrian University of Athens
Lead sponsor
AstraZeneca
Collaborator
