Daratumumab in Primary Antiphospholipid Syndrome

NCT05671757 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: DAIT ITN093AI
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Autoimmune Disorders

Keywords

Daratumumab; Anti-Phospholipid Syndrome

Outcome Measures

Primary Outcomes (1)

• 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

  At or before week 9

Secondary Outcomes (15)

• The proportion of Grade 2 or higher adverse event (AEs) and serious adverse events (SAEs) related to daratumumab

  At or before weeks 9, 24, and 48

• The proportion of participants with the following Grade 3 or higher adverse events (AEs) related to daratumumab

  At or before weeks 9, 24, and 48.

• The proportion of participants with negative Lupus Anticoagulant (LA) test

  At week 9

• The proportion of participants with at least 50% reduction in Anticardiolipin antibodies Immunoglobulin G (aCL IgG)

  At week 9 compared to week 0

• The proportion of participants with at least 50% reduction in Anti-beta2-glycoprotein test Immunoglobulin G (abeta2GPI IgG) levels

  At week 9 compared to week 0

Study Arms (3)

4 mg/kg Cohort

EXPERIMENTAL

This cohort will receive intravenous (IV) administration of 4 mg/kg 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

Biological: Daratumumab

8 mg/kg Cohort

EXPERIMENTAL

This cohort will receive intravenous (IV) administration of 8 mg/kg 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

Biological: Daratumumab

16 mg/kg Cohort

EXPERIMENTAL

This cohort will receive intravenous (IV) administration of 16 mg/kg 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

Biological: Daratumumab

Interventions

Daratumumab BIOLOGICAL

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

Also known as: DARZALEX, DARZALEX®

4 mg/kg Cohort

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Immune Tolerance Network (ITN): collaborator
• PPD Development, LP: collaborator
• Rho Federal Systems Division, Inc.: collaborator

Study Sites (8)

Johns Hopkins University

Baltimore, Maryland, 21205, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

COMPLETED

Northwell Health

Great Neck, New York, 11021, United States

RECRUITING

NYU Langone

New York, New York, 10016, United States

RECRUITING

Hospital for Special Surgery

New York, New York, 10021, United States

RECRUITING

Weill Cornell

New York, New York, 10021, United States

RECRUITING

Duke University

Durham, North Carolina, 27710, United States

RECRUITING

Related Links

• Immune Tolerance Network
• National Institute of Allergy and Infectious Diseases
• Division of Allergy, Immunology, and Transplantation

MeSH Terms

Conditions

Autoimmune Diseases; Antiphospholipid Syndrome

Interventions

daratumumab

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Doruk Erkan, M.D., M.P.H.

  Hospital for Special Surgery, New York: Division of Rheumatology

  STUDY CHAIR

• Jason Knight, M.D., Ph.D.

  University of Michigan Health System: Department of Internal Medicine, Division of Rheumatology

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2022
• First Posted: January 5, 2023
• Study Start: May 26, 2023
• Primary Completion (Estimated): June 24, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 2, 2026

Record last verified: 2026-03

Locations

US (8)