Antiphospholipid Syndrome (APS)
Conditions
Brief summary
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.
Interventions
DRUGAnifrolumab
Anifrolumab 120 mg administered subcutaneously once weekly for up to 52 weeks in addition to standard of care treatment.
Sponsors
National and Kapodistrian University of Athens
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Provision of written informed consent (ICF) prior to any study-specific procedures. 2. Females/males aged 18 to 70 years at Screening (at the time of ICF signing). 3. Weight ≥40.0 kg at Screening. 4. 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. 5. For females of childbearing potential only: Negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test at Screening. 6. 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. 7. 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. 8. 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. 9. Meeting all the following TB criteria: 1. 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. 2. No signs or symptoms suggestive of active TB from medical history or physical examination 3. 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. 4. 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. 10. 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. 11. Negative SARs-CoV-2 polymerase chain reaction (PCR) or antigen test result as per local policies at Screening. 12. 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.
Exclusion criteria
* General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of anifrolumab | by week 52 | Incidence of adverse events (AEs) including adverse events of special interest \[AESIs; i.e., opportunistic infections, serious non-opportunistic infections, herpes zoster, influenza, malignancies, anaphylaxis\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics (PD) of anifrolumab | baseline-week 24-week 52 | 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 | from baseline to weeks 12, 24 and 52 | Change from baseline in aCL and aβ2GPI IgG antibody titres at weeks 12, 24 and 52 |
| Effect of anifrolumab on the patients' immunological profile | from baseline to weeks 24 and 52 | Change from baseline in lupus anticoagulant (LA) status at weeks 24 and 52 |
| Effect of anifrolumab on thrombin generation | from baseline to weeks 24 and 52 | Change from baseline in endogenous thrombin potential, as assessed by a thrombin generation assay at weeks 24 and 52 |
| Effect of anifrolumab on neutrophil extracellular trap (NET) release | from baseline to weeks 24 and 52 | Change from baseline in the levels of ΝET release markers \[i.e., myeloperoxidase (MPO), citrullinated histone H3 (H3Cit) and MPO-deoxyribonucleic acid (DNA) complexes), as assessed by immunofluorescence confocal microscopy and enzyme-linked immunosorbent assay (ELISA) at weeks 24 and 52 |
| The effect of anifrolumab on thromboinflammation-related gene expression | from baseline to weeks 24 and 52 | Change from baseline in immunothrombosis/thromboinflammation-related gene expression, as assessed by bulk ribonucleic acid (RNA) sequencing at weeks 24 and 52 |
| The effect of anifrolumab on health-related quality of life (HRQL) and other patient-reported outcomes (PROs) | From baseline to weeks 4, 12, 24, 36, 48 and 52 | Change from baseline in the 36-Item Short Form Survey version 2 (SF-36v2) score at weeks 4, 12, 24, 36, 48 and 52 |
| Physician's global assessment of patient's health status | From baseline to weeks 4, 12, 24, 36, 48 and 52 | Change from baseline in the Physician's Global Assessment of patient's health status (PhGA) score at weeks 4, 12, 24, 36, 48 and 52 |
Countries
Greece
Contacts
CONTACTMaria G Tektonidou, MD, PhD
Outcome results
None listed