Daratumumab in Primary Antiphospholipid Syndrome

Recruiting now · Phase 1/Phase 2

Conditions studied: Autoimmune Disorders

In brief

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.

Key facts

Study ID

NCT05671757

Run by

National Institute of Allergy and Infectious Diseases (NIAID)

People needed

22

Starts

2023-05-26

Expected to finish

2027-03-01

Last updated by the study team

2026-04-02

Who can join

Age: 18 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

You may not qualify if…

• Inability or unwillingness to give written informed consent.
• Inability or unwillingness to comply with study protocol.
• Systemic autoimmune diseases other than APS, including but not limited to:
• Systemic lupus erythematosus (SLE) meeting the EULAR/ACR classification criteria.
• Rheumatoid arthritis meeting the ACR/EULAR classification criteria.
• Small, medium, and large vessel vasculitis meeting ACR classification criteria.
• Catastrophic APS classification within the prior 90 days.
• Acute arterial or venous thrombosis within the prior 30 days.
• Use of the following medications:
• Any prior treatment with CD38 targeting monoclonal antibodies, including daratumumab or isatuximab-irfc.
• The following within the prior 30 days:
• i. Corticosteroids > 10 mg/day prednisone or equivalent. ii. Direct oral anticoagulants (DOACs). iii. Live attenuated vaccines. iv. IVIG or other supplemental immunoglobulin. c. Azathioprine, methotrexate, mycophenolate mofetil, mycophenolate sodium, lefluonomide, or calcineurin inhibitors within the prior 90 days.
• d. Cyclophosphamide within the prior 90 days. e. Immunomodulatory or immunosuppressive biologic agents, including belimumab, within the prior 90 days or 5 half-lives, whichever is greater.
• f. Investigational agents within the prior 90 days or 5 half-lives, whichever is greater, except for COVID-19 vaccines and medications for prevention or treatment of COVID-19 per FDA Emergency Use Authorization (EUA).
• g. Biologic B cell depleting agents including rituximab with any of the following: i. Treatment within the prior 180 days, or ii. CD19+ absolute count < 40/ μl, or iii. Serum IgG <500 mg/dL.
• Plasma exchange within the prior 90 days.
• Hemodialysis within the prior 90 days.
• Major surgical procedure within the prior 60 days.
• Known allergy, hypersensitivity, or intolerance to boron, malitol, sorbitol, corticosteroids, monoclonal antibodies including daratumumab, human proteins, or their excipients.
• Allergy, intolerance, or contraindication to acyclovir, valacyclovir, and famciclovir.
• Active or chronic infection, including the following:
• Active bacterial, viral, fungal, or opportunistic infection.
• Chronic infection requiring suppressive antibiotic treatment.
• Intravenous antibiotics or hospitalization for infection within the prior 30 days.
• Evidence of current or prior Mycobacterium tuberculosis infection.

Where it is running

• Duke University — Durham, North Carolina, United States (enrolling)
• University of Michigan — Ann Arbor, Michigan, United States (enrolling)
• Johns Hopkins University — Baltimore, Maryland, United States (enrolling)
• Northwell Health — Great Neck, New York, United States (enrolling)
• NYU Langone — New York, New York, United States (enrolling)
• Hospital for Special Surgery — New York, New York, United States (enrolling)
• Weill Cornell — New York, New York, United States (enrolling)
• Mayo Clinic Rochester — Rochester, Minnesota, United States

Full record on ClinicalTrials.gov

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