A Phase II Open-Label Pilot Trial Assessing the Safety of Anifrolumab in Adult Patients With Primary Antiphospholipid Syndrome (APS). The AnifAPS Trial
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.
• Note: Patients with obstetric manifestations will be excluded from this study.
• For females of childbearing potential only: Negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test at Screening.
• Females of childbearing potential must be willing to use a highly effective method of contraception (failure rate of \<1% per year when used consistently and correctly) throughout their participation in the study, i.e., from Screening and for up to 20 weeks after the last dose of IP. Examples of highly effective methods of contraception are located in Appendix C, Contraceptive and Barrier Guidance.
• Male patients who are sexually active with a female partner of childbearing potential must be willing to use a condom (with spermicide where commercially available) throughout their participation in the study, i.e., from Screening and for up to 20 weeks after the last dose of IP.
• Male patients must not donate sperm during the course of the study and for up to 20 weeks after the last dose of the IP.
• Meeting all the following TB criteria:
∙ No history of latent or active TB prior to Screening, except for latent TB with documented completion of appropriate treatment as per local SoC Note: Subjects with no history of latent TB prior to the initial Screening visit, but who are diagnosed with latent TB during the Screening Period, may be considered eligible if appropriate treatment is initiated prior to first administration of IP as per local SoC. Such subjects may be re-screened if necessary to allow for local guidelines on latent TB treatment initiation.
‣ No signs or symptoms suggestive of active TB from medical history or physical examination
‣ No recent contact with a person with active TB OR if there has been such contact, referral to a physician specialising in TB to undergo additional evaluation prior to first administration of IP (documented appropriately in source), and, if warranted, receipt of appropriate treatment for latent TB at or prior to first administration of IP as per local SoC.
‣ Must meet 1 of the following criteria:
• (i)Negative QuantiFERON-TB Gold (QFT-G) test result for TB obtained within 4 weeks prior to Week 0 (Day 1) OR (ii)Positive QFT-G test result for TB obtained during the Screening Period for which active TB has been ruled out and appropriate treatment for latent TB has been initiated prior to first administration of IP as per local SoC OR (iii)Indeterminate (confirmed on retest) QFT-G test result for TB obtained during the Screening Period with ongoing QFT-G testing for TB as clinically indicated.
⁃ Chest x-ray \[or lung CT\*, where available\] with no evidence of current active infection (eg, TB) or previous old active TB, malignancy, or clinically significant abnormalities (unless due to APS) obtained during the Screening Period or anytime within 12 weeks prior to signing the ICF.
⁃ Negative SARs-CoV-2 polymerase chain reaction (PCR) or antigen test result as per local policies at Screening.
⁃ Females with an intact cervix must have documentation of a normal Pap smear with no documented malignancy (e.g., cervical intraepithelial neoplasia grade III \[CIN III\], carcinoma in situ \[CIS\], or adenocarcinoma in situ \[AIS\]) within 2 years prior to Week 0 (Day 1) (see Appendix E for guidance on abnormal Pap smear results).
• Note: Any abnormal Pap smear result documented within 2 years prior to randomisation must be repeated to confirm patient eligibility. See also Exclusion criterion 23b.