Daratumumab in Primary Antiphospholipid Syndrome

Eligibility Criteria

• 1. Adults 18 to 70 years of age, inclusive.
• 2. The completion of the following vaccinations at least 14 days prior to Visit 0:
• 1. At least one dose of the most recently updated COVID-19 vaccine, and
• 2. At least one dose of the herpes zoster vaccination series, and
• 3. Current seasonal influenza vaccine, if available.
• 3. History of APS according to the updated 2006 Sapporo classification criteria, including at least one of the following:
• 4. History of triple positive aPL within the prior 5 years and at least 12 weeks prior to enrollment, including all of the following:
• 1. aCL IgG level \> Upper Limit of Normal (ULN), and
• 2. aβ2GPI IgG level \> ULN, and
• 3. Positive LA test.
• 5. Confirmation of triple positive aPL at screening, including all of the following:
• 1. aCL IgG level ≥ 40 GPL, and
• 2. aβ2GPI IgG level ≥ 40 SGU, and
• 3. Positive LA test.
• 6. Undergoing anticoagulation with warfarin or low molecular weight heparin (LMWH), if there is a history of arterial or venous thrombosis.
• 1. Inability or unwillingness to give written informed consent.
• 2. Inability or unwillingness to comply with study protocol.
• 3. Systemic autoimmune diseases other than APS, including but not limited to:
• 1. Systemic lupus erythematosus (SLE) meeting the EULAR/ACR classification criteria.
• 2. Rheumatoid arthritis meeting the ACR/EULAR classification criteria.
• 3. Small, medium, and large vessel vasculitis meeting ACR classification criteria.
• 4. Catastrophic APS classification within the prior 90 days.
• 5. Acute arterial or venous thrombosis within the prior 30 days.
• 6. Use of the following medications:
• 1. Any prior treatment with CD38 targeting monoclonal antibodies, including daratumumab or isatuximab-irfc.
• 2. Administration of the Janssen COVID-19 vaccine within the prior 14 days.
• 3. The following within the prior 30 days:
• 7. Plasma exchange within the prior 90 days.
• 8. Hemodialysis within the prior 90 days.
• 9. Major surgical procedure within the prior 60 days.
• 10. Known allergy, hypersensitivity, or intolerance to boron, malitol, sorbitol, corticosteroids, monoclonal antibodies including daratumumab, human proteins, or their excipients.
• 11. Allergy, intolerance, or contraindication to acyclovir, valacyclovir, and famciclovir.
• 12. Active or chronic infection, including the following:
• 1. Active bacterial, viral, fungal, or opportunistic infection.
• 2. Chronic infection requiring suppressive antibiotic treatment.
• 3. Intravenous antibiotics or hospitalization for infection within the prior 30 days.
• 4. Evidence of current or prior Mycobacterium tuberculosis infection.
• 5. Human immunodeficiency virus (HIV).
• 6. Current or prior infection with hepatitis B virus (HBV).
• 7. Current or prior infection with hepatitis C virus (HCV), except adequately treated HCV with sustained virologic response ≥ 12 weeks.
• 8. History of recurrent herpes zoster, or history of herpes zoster ophthalmicus, disseminated herpes zoster, or disseminated herpes simplex.
• 13. The following laboratory abnormalities:
• 1. Absolute neutrophil count \< 1500/mm3.
• 2. Platelets \< 100,000/mm3.
• 3. Hemoglobin (Hgb) \< 10 g/dL.
• 4. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase \> 2x the Upper Limit of Normal (ULN).
• 5. Total bilirubin \> 2x ULN, except in the case of congenital bilirubinemia then direct bilirubin \> 2x ULN.
• 6. eGFR \< 45 ml/min/1.73 m2.
• 14. History of primary immunodeficiency.
• 15. History of solid organ or hematopoietic stem cell transplantation.
• 16. Comorbidities requiring systemic corticosteroid therapy, including those which have required three or more courses of systemic corticosteroids within the 12 months prior to Visit 0.
• 17. Any of the following conditions with FEV1 \< 70% predicted within the prior 90 days:
• 1. Asthma.
• 2. Chronic obstructive pulmonary disease (COPD).
• 3. DAH.
• 18. Pulmonary hypertension.
• 19. Adrenal insufficiency.
• 20. Poorly controlled diabetes mellitus defined as hemoglobin A1c (HbA1c) ≥ 8.0%.
• 21. Concomitant malignancy or history of malignancy, except adequately treated or excised nonmetastatic squamous cell carcinoma, basal cell skin carcinoma, or cervical carcinoma in situ.
• 22. Clinically significant cardiac disease, including but not limited to:
• 1. Myocardial infarction within the prior 6 months, or
• 2. Unstable or uncontrolled disease or condition related to or affecting cardiac function, including but not limited to:
• 23. Current diagnosed mental illness or current diagnosed or self-reported drug or alcohol abuse which, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.
• 24. Severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, or neurological disease.
• 25. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements, or may impact the quality or interpretation of the data obtained from the study.
• 26. Lack of peripheral venous access.
• 27. Pregnancy, or planning a pregnancy during the 48 week study duration.
• 28. Breast-feeding.
• 29. Unwillingness to use medically acceptable non-prothrombotic contraception if of reproductive potential and engaging in sexual activity that could lead to pregnancy.