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.
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.
Inability or unwillingness to give written informed consent.
Inability or unwillingness to comply with study protocol.
Systemic lupus erythematosus (SLE) meeting the EULAR/ACR classification criteria.
Rheumatoid arthritis meeting the ACR/EULAR classification criteria.
Parallel
Daratumumab
Biological/VaccineParticipants will receive 4 mg/kg of intravenous (IV) daratumumab administered weekly for 8 doses (weeks 0 through 7). Post-treatment follow-up visits will occur at weeks 9, 12, 18, 24, 36, and 48
Daratumumab
Biological/VaccineParticipants will receive 4-8 mg/kg of intravenous (IV) daratumumab administered weekly for 8 doses (weeks 0 through 7). Post-treatment follow-up visits will occur at weeks 9, 12, 18, 24, 36, and 48
Daratumumab
Biological/VaccineParticipants will receive 4-16 mg/kg of intravenous (IV) daratumumab administered weekly for 8 doses (weeks 0 through 7). Post-treatment follow-up visits will occur at weeks 9, 12, 18, 24, 36, and 48
The proportion of participants in the dose escalation phase with at least one Dose Limiting Toxicity (DLT)
Proportions will be estimated by dose cohort with 95% confidence intervals derived using the Clopper-Pearson exact method
The proportion of Grade 2 or higher adverse event (AEs) and serious adverse events (SAEs) related to daratumumab
The proportion of participants who experience at least one event will be estimated by dosing level with 90% confidence intervals derived using the Clopper-Pearson exact method
The proportion of participants with the following Grade 3 or higher adverse events (AEs) related to daratumumab
Adverse events including: 1. Infusion reaction 2. Neutropenia 3. Thrombocytopenia 4. Infection
The proportion of participants with negative Lupus Anticoagulant (LA) test
For dichotomous endpoints, including the composite of (a) Negative LA test, and (b) fold-reduction in both aCL IgG and aß2GPI IgG, and the individual components, proportions will be reported with 90% confidence intervals derived using the Clopper-Pearson exact method
The proportion of participants with at least 50% reduction in Anticardiolipin antibodies Immunoglobulin G (aCL IgG)
For dichotomous endpoints, including the composite of (a) Negative LA test, and (b) fold-reduction in both aCL IgG and aß2GPI IgG, and the individual components, proportions will be reported with 90% confidence intervals derived using the Clopper-Pearson exact method
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National Institute of Allergy and Infectious Diseases (NIAID)
Lead sponsor
Immune Tolerance Network (ITN)
Collaborator
PPD Development, LP
Collaborator
Rho Federal Systems Division, Inc.
Collaborator
