RECRUITING

Daratumumab in Primary Antiphospholipid Syndrome

Conditions

Autoimmune Disorders Daratumumab Anti-Phospholipid Syndrome

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Targeting CD38 With Daratumumab in Primary Antiphospholipid Syndrome: A Phase 1b Dose Escalation Safety Trial (ITN093AI)

Quick Facts

Study Start:2023-05-26

Study Completion:2027-03

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05671757

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 65 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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: 4. History of triple positive aPL within the prior 5 years and at least 12 weeks prior to enrollment, including all of the following: 1. aCL IgG level \> Upper Limit of Normal (ULN), and 2. aβ2GPI IgG level \> ULN, and 3. Positive LA test. 5. Confirmation of triple positive aPL at screening, including all of the following: 1. aCL IgG level ≥ 40 GPL, and 2. aβ2GPI IgG level ≥ 40 SGU, and 3. Positive LA test. 6. Undergoing anticoagulation with warfarin or low molecular weight heparin (LMWH), if there is a history of arterial or venous thrombosis.	1. Inability or unwillingness to give written informed consent. 2. Inability or unwillingness to comply with study protocol. 3. Systemic autoimmune diseases other than APS, including but not limited to: 1. Systemic lupus erythematosus (SLE) meeting the EULAR/ACR classification criteria. 2. Rheumatoid arthritis meeting the ACR/EULAR classification criteria. 3. Small, medium, and large vessel vasculitis meeting ACR classification criteria. 4. Catastrophic APS classification within the prior 90 days. 5. Acute arterial or venous thrombosis within the prior 30 days. 6. Use of the following medications: 1. Any prior treatment with CD38 targeting monoclonal antibodies, including daratumumab or isatuximab-irfc. 2. Administration of the Janssen COVID-19 vaccine within the prior 14 days. 3. The following within the prior 30 days: 7. Plasma exchange within the prior 90 days. 8. Hemodialysis within the prior 90 days. 9. Major surgical procedure within the prior 60 days. 10. Known allergy, hypersensitivity, or intolerance to boron, malitol, sorbitol, corticosteroids, monoclonal antibodies including daratumumab, human proteins, or their excipients. 11. Allergy, intolerance, or contraindication to acyclovir, valacyclovir, and famciclovir. 12. Active or chronic infection, including the following: 1. Active bacterial, viral, fungal, or opportunistic infection. 2. Chronic infection requiring suppressive antibiotic treatment. 3. Intravenous antibiotics or hospitalization for infection within the prior 30 days. 4. Evidence of current or prior Mycobacterium tuberculosis infection. 5. Human immunodeficiency virus (HIV). 6. Current or prior infection with hepatitis B virus (HBV). 7. Current or prior infection with hepatitis C virus (HCV), except adequately treated HCV with sustained virologic response ≥ 12 weeks. 8. History of recurrent herpes zoster, or history of herpes zoster ophthalmicus, disseminated herpes zoster, or disseminated herpes simplex. 13. The following laboratory abnormalities: 1. Absolute neutrophil count \< 1500/mm3. 2. Platelets \< 100,000/mm3. 3. Hemoglobin (Hgb) \< 10 g/dL. 4. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase \> 2x the Upper Limit of Normal (ULN). 5. Total bilirubin \> 2x ULN, except in the case of congenital bilirubinemia then direct bilirubin \> 2x ULN. 6. eGFR \< 45 ml/min/1.73 m2. 14. History of primary immunodeficiency. 15. History of solid organ or hematopoietic stem cell transplantation. 16. Comorbidities requiring systemic corticosteroid therapy, including those which have required three or more courses of systemic corticosteroids within the 12 months prior to Visit 0. 17. Any of the following conditions with FEV1 \< 70% predicted within the prior 90 days: 1. Asthma. 2. Chronic obstructive pulmonary disease (COPD). 3. DAH. 18. Pulmonary hypertension. 19. Adrenal insufficiency. 20. Poorly controlled diabetes mellitus defined as hemoglobin A1c (HbA1c) ≥ 8.0%. 21. Concomitant malignancy or history of malignancy, except adequately treated or excised nonmetastatic squamous cell carcinoma, basal cell skin carcinoma, or cervical carcinoma in situ. 22. Clinically significant cardiac disease, including but not limited to: 1. Myocardial infarction within the prior 6 months, or 2. Unstable or uncontrolled disease or condition related to or affecting cardiac function, including but not limited to: 23. Current diagnosed mental illness or current diagnosed or self-reported drug or alcohol abuse which, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements. 24. Severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, or neurological disease. 25. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements, or may impact the quality or interpretation of the data obtained from the study. 26. Lack of peripheral venous access. 27. Pregnancy, or planning a pregnancy during the 48 week study duration. 28. Breast-feeding. 29. Unwillingness to use medically acceptable non-prothrombotic contraception if of reproductive potential and engaging in sexual activity that could lead to pregnancy.

Inclusion Criteria

Exclusion 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:
4. History of triple positive aPL within the prior 5 years and at least 12 weeks prior to enrollment, including all of the following:
1. aCL IgG level \> Upper Limit of Normal (ULN), and
2. aβ2GPI IgG level \> ULN, and
3. Positive LA test.
5. Confirmation of triple positive aPL at screening, including all of the following:
1. aCL IgG level ≥ 40 GPL, and
2. aβ2GPI IgG level ≥ 40 SGU, and
3. Positive LA test.
6. Undergoing anticoagulation with warfarin or low molecular weight heparin (LMWH), if there is a history of arterial or venous thrombosis.

1. Inability or unwillingness to give written informed consent.
2. Inability or unwillingness to comply with study protocol.
3. Systemic autoimmune diseases other than APS, including but not limited to:
1. Systemic lupus erythematosus (SLE) meeting the EULAR/ACR classification criteria.
2. Rheumatoid arthritis meeting the ACR/EULAR classification criteria.
3. Small, medium, and large vessel vasculitis meeting ACR classification criteria.
4. Catastrophic APS classification within the prior 90 days.
5. Acute arterial or venous thrombosis within the prior 30 days.
6. Use of the following medications:
1. Any prior treatment with CD38 targeting monoclonal antibodies, including daratumumab or isatuximab-irfc.
2. Administration of the Janssen COVID-19 vaccine within the prior 14 days.
3. The following within the prior 30 days:
7. Plasma exchange within the prior 90 days.
8. Hemodialysis within the prior 90 days.
9. Major surgical procedure within the prior 60 days.
10. Known allergy, hypersensitivity, or intolerance to boron, malitol, sorbitol, corticosteroids, monoclonal antibodies including daratumumab, human proteins, or their excipients.
11. Allergy, intolerance, or contraindication to acyclovir, valacyclovir, and famciclovir.
12. Active or chronic infection, including the following:
1. Active bacterial, viral, fungal, or opportunistic infection.
2. Chronic infection requiring suppressive antibiotic treatment.
3. Intravenous antibiotics or hospitalization for infection within the prior 30 days.
4. Evidence of current or prior Mycobacterium tuberculosis infection.
5. Human immunodeficiency virus (HIV).
6. Current or prior infection with hepatitis B virus (HBV).
7. Current or prior infection with hepatitis C virus (HCV), except adequately treated HCV with sustained virologic response ≥ 12 weeks.
8. History of recurrent herpes zoster, or history of herpes zoster ophthalmicus, disseminated herpes zoster, or disseminated herpes simplex.
13. The following laboratory abnormalities:
1. Absolute neutrophil count \< 1500/mm3.
2. Platelets \< 100,000/mm3.
3. Hemoglobin (Hgb) \< 10 g/dL.
4. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase \> 2x the Upper Limit of Normal (ULN).
5. Total bilirubin \> 2x ULN, except in the case of congenital bilirubinemia then direct bilirubin \> 2x ULN.
6. eGFR \< 45 ml/min/1.73 m2.
14. History of primary immunodeficiency.
15. History of solid organ or hematopoietic stem cell transplantation.
16. Comorbidities requiring systemic corticosteroid therapy, including those which have required three or more courses of systemic corticosteroids within the 12 months prior to Visit 0.
17. Any of the following conditions with FEV1 \< 70% predicted within the prior 90 days:
1. Asthma.
2. Chronic obstructive pulmonary disease (COPD).
3. DAH.
18. Pulmonary hypertension.
19. Adrenal insufficiency.
20. Poorly controlled diabetes mellitus defined as hemoglobin A1c (HbA1c) ≥ 8.0%.
21. Concomitant malignancy or history of malignancy, except adequately treated or excised nonmetastatic squamous cell carcinoma, basal cell skin carcinoma, or cervical carcinoma in situ.
22. Clinically significant cardiac disease, including but not limited to:
1. Myocardial infarction within the prior 6 months, or
2. Unstable or uncontrolled disease or condition related to or affecting cardiac function, including but not limited to:
23. Current diagnosed mental illness or current diagnosed or self-reported drug or alcohol abuse which, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.
24. Severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, or neurological disease.
25. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements, or may impact the quality or interpretation of the data obtained from the study.
26. Lack of peripheral venous access.
27. Pregnancy, or planning a pregnancy during the 48 week study duration.
28. Breast-feeding.
29. Unwillingness to use medically acceptable non-prothrombotic contraception if of reproductive potential and engaging in sexual activity that could lead to pregnancy.

Contacts and Locations

Principal Investigator

Doruk Erkan, M.D., M.P.H.

STUDY_CHAIR

Hospital for Special Surgery, New York: Division of Rheumatology

Jason Knight, M.D., Ph.D.

STUDY_CHAIR

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

Study Locations (Sites)

Johns Hopkins University

Baltimore, Maryland, 21205

United States

University of Michigan

Ann Arbor, Michigan, 48109

United States

Mayo Clinic Rochester

Rochester, Minnesota, 55905

United States

Northwell Health

Great Neck, New York, 11021

United States

NYU Langone

New York, New York, 10016

United States

Hospital for Special Surgery

New York, New York, 10021

United States

Weill Cornell

New York, New York, 10021

United States

Duke University

Durham, North Carolina, 27710

United States

Collaborators and Investigators

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Doruk Erkan, M.D., M.P.H., STUDY_CHAIR, Hospital for Special Surgery, New York: Division of Rheumatology
Jason Knight, M.D., Ph.D., STUDY_CHAIR, University of Michigan Health System: Department of Internal Medicine, Division of Rheumatology

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-05-26

Study Completion Date2027-03

Study Record Updates

Study Start Date2023-05-26

Study Completion Date2027-03

Terms related to this study

Keywords Provided by Researchers

Daratumumab
Anti-Phospholipid Syndrome

Additional Relevant MeSH Terms

Autoimmune Disorders