Targeting CD38 With Daratumumab in Primary Antiphospholipid Syndrome: A Phase 1b Dose Escalation Safety Trial (ITN093AI)
National Institute of Allergy and Infectious Diseases (NIAID)
Summary
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.
Description
The trial is a phase 1b open-label study of daratumumab in participants with APS. The study design is a modification of the 3 + 3 dose escalation scheme. Three daratumumab dose cohorts are planned: 4 mg/kg, 8 mg/kg, and 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. Dose Escalation Phase Dose escalation will proceed according to safety criteria (Dose Limiting Toxicity, DLT) and efficacy criteria (antiphospholipid antibody negativity). An independent safety committee w…
Eligibility
- Age range
- 18–65 years
- Sex
- All
- Healthy volunteers
- No
Inclusion 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: a. Arterial thrombosis, except transient ischemic attack, confirmed by objective validated criteria such as imaging, or b. Ve…
Interventions
- BiologicalDaratumumab
Participants 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
- BiologicalDaratumumab
Participants 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
- BiologicalDaratumumab
Participants 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
Locations (8)
- Johns Hopkins UniversityBaltimore, Maryland
- University of MichiganAnn Arbor, Michigan
- Mayo Clinic RochesterRochester, Minnesota
- Northwell HealthGreat Neck, New York
- NYU LangoneNew York, New York
- Hospital for Special SurgeryNew York, New York