Targeting CD38 With Daratumumab in Primary Antiphospholipid Syndrome: A Phase 1b Dose Escalation Safety Trial (ITN093AI)
The purpose of this study is to see if the study medication, daratumumab, is safe to treat individuals with Anti-Phospholipid Syndrome (APS). Three daratumumab dosing cohorts are planned with up to six participants in each dosing cohort with the potential to enroll an additional 4 subjects in the highest safe dose (HSD) cohort, for a total of up to 22 participants. The dosing cohorts are: 4 mg/kg, 8 mg/kg, and 16 mg/kg. Each cohort will receive intravenous (IV) administration of daratumumab according to the following schedule, for a total of 8 doses. The primary objective is to determine the safety of daratumumab in APS defined as Dose Limiting Toxicities (DLTs) occurring during the dose escalation phase.
• Adults 18 to 70 years of age, inclusive.
• The completion of the following vaccinations at least 14 days prior to Visit 0:
‣ At least one dose of the most recently updated COVID-19 vaccine, and
⁃ At least one dose of the herpes zoster vaccination series, and
⁃ Current seasonal influenza vaccine, if available.
• History of APS according to the updated 2006 Sapporo classification criteria, including at least one of the following:
• a. Arterial thrombosis, except transient ischemic attack, confirmed by objective validated criteria such as imaging, or b. Venous thrombosis, except superficial thrombophlebitis, confirmed by objective validated criteria such as imaging, or c. Pregnancy morbidity, based on the updated 2006 Sapporo APS classification criteria, or d. Microvascular APS, with at least one of the following: i. Renal biopsy documentation of aPL-associated nephropathy, or ii. Lung biopsy or bronchoalveolar lavage documentation of diffuse alveolar hemorrhage (DAH), or iii. Skin biopsy documentation of livedoid vasculopathy.
• History of triple positive aPL within the prior 5 years and at least 12 weeks prior to enrollment, including all of the following:
‣ aCL IgG level \> Upper Limit of Normal (ULN), and
⁃ aβ2GPI IgG level \> ULN, and
⁃ Positive LA test.
• Confirmation of triple positive aPL at screening, including all of the following:
‣ aCL IgG level ≥ 40 GPL, and
⁃ aβ2GPI IgG level ≥ 40 SGU, and
⁃ Positive LA test.
• Undergoing anticoagulation with warfarin or low molecular weight heparin (LMWH), if there is a history of arterial or venous thrombosis.