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Number of Visits: 22

22 Participants Needed

Daratumumab for Antiphospholipid Syndrome
(DARE-APS Trial)

Recruiting at 7 trial locations

Overseen ByShruti Chaturvedi

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

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

Must be taking: Warfarin, LMWH

Must not be taking: Corticosteroids, DOACs, Biologics, others

Disqualifiers: Systemic autoimmune diseases, Active infection, others

No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a medication called daratumumab for individuals with Antiphospholipid Syndrome (APS), a condition where the immune system mistakenly attacks normal blood proteins, leading to blood clots. Participants will receive varying doses of daratumumab to determine the safest dose and identify any side effects. Suitable candidates have confirmed APS through blood tests and have experienced blood clots or specific pregnancy issues related to APS. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before participating. Specifically, you must not have used corticosteroids over 10 mg/day, direct oral anticoagulants, certain immunosuppressive drugs, or biologic agents within specified time frames before joining the study. If you are on warfarin or low molecular weight heparin due to a history of thrombosis, you may continue these medications.

Is there any evidence suggesting that daratumumab is likely to be safe for humans?

Research shows that patients generally tolerate daratumumab well. In studies involving patients with relapsed or hard-to-treat multiple myeloma, daratumumab was tolerated equally well whether administered as an injection under the skin or through an IV, resulting in similar side effects regardless of the method.

However, some serious reactions have been reported. In certain cases, daratumumab treatments have caused severe reactions, including a few fatal ones. Therefore, participants must be closely monitored during treatment.

Daratumumab is already approved for other conditions, indicating that its safety has been thoroughly studied. This trial will specifically examine its safety for treating Anti-Phospholipid Syndrome (APS). Participants will receive varying doses to assess their tolerance. The goal is to identify the highest safe dose without causing major side effects.¹ ² ³ ⁴ ⁵

Why do researchers think this study treatment might be promising for Antiphospholipid Syndrome?

Daratumumab is unique because it targets CD38, a protein commonly found on the surface of certain immune cells. This is different from the standard treatments for Antiphospholipid Syndrome, which typically include blood thinners like warfarin or aspirin. Researchers are excited about daratumumab because it offers a novel mechanism of action, potentially reducing the risk of blood clots by modulating immune cell activity rather than just thinning the blood. Additionally, daratumumab is administered intravenously, which may provide more consistent dosing compared to oral medications.

What evidence suggests that daratumumab might be an effective treatment for Antiphospholipid Syndrome?

Research has shown that daratumumab holds promise for treating multiple myeloma, a type of blood cancer. One study found that many patients responded positively to the treatment. Specifically, 63.4% of patients responded well to DARZALEX FASPRO®, a form of daratumumab, compared to only 2% with other treatments, indicating its potential effectiveness. In this trial, researchers are studying daratumumab for antiphospholipid syndrome (APS) across different dosage cohorts. While these early results from other conditions are encouraging, the current study will evaluate its effectiveness specifically for APS. The treatment works by attaching to a specific protein on certain cells, aiding the immune system in attacking those cells.¹ ² ³ ⁶ ⁷

Who Is on the Research Team?

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

Principal Investigator

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

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

Principal Investigator

Hospital for Special Surgery, New York: Division of Rheumatology

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with Anti-Phospholipid Syndrome (APS), who meet specific criteria including a history of certain types of thrombosis or pregnancy complications related to APS. Participants must have completed recommended vaccinations, be willing to use warfarin or LMWH for anticoagulation, and not have other autoimmune disorders like rheumatoid arthritis or systemic lupus erythematosus.

Inclusion Criteria

History of triple positive aPL within the prior 5 years and at least 12 weeks prior to enrollment

Willing and able to discontinue direct oral anticoagulants if applicable

I am willing to take blood thinners if I have a history of blood clots.

See 3 more

Exclusion Criteria

Inability or unwillingness to give written informed consent

Inability or unwillingness to comply with study protocol

I have an ongoing infection.

See 23 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive weekly intravenous administration of daratumumab for 8 doses to determine the highest safe dose

8 weeks

8 visits (in-person)

Expansion Phase

Four additional participants are treated at the highest safe dose weekly for 8 doses

8 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 weeks

6 visits (in-person) at weeks 9, 12, 18, 24, 36, and 48

What Are the Treatments Tested in This Trial?

Interventions

Daratumumab

Trial Overview The study tests the safety of daratumumab at different doses (4 mg/kg, 8 mg/kg, and 16 mg/kg) in treating APS. Up to 22 participants will receive intravenous doses on a set schedule to identify any dose-limiting toxicities during this phase.

How Is the Trial Designed?

3Treatment groups

Experimental Treatment

Group I: 8 mg/kg CohortExperimental Treatment1 Intervention

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

Group II: 4 mg/kg CohortExperimental Treatment1 Intervention

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

Group III: 16 mg/kg CohortExperimental Treatment1 Intervention

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

Daratumumab is already approved in European Union, United States for the following indications:

Approved in European Union as Darzalex for:

Relapsed and refractory multiple myeloma
Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone

Approved in United States as Darzalex for:

Multiple myeloma in patients who have received at least three prior therapies
Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone
Relapsed or refractory multiple myeloma in combination with lenalidomide and dexamethasone

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

PPD DEVELOPMENT, LP

Industry Sponsor

Trials

167

Recruited

38,000+

David Simmons

PPD DEVELOPMENT, LP

Chief Executive Officer since 2012

BSc in Applied Science from Georgia Institute of Technology

Martina Flammer

PPD DEVELOPMENT, LP

Chief Medical Officer since 2024

PPD Development, LP

Industry Sponsor

Immune Tolerance Network (ITN)

Collaborator

Trials

Recruited

7,900+

PPD

Industry Sponsor

Trials

162

Recruited

36,600+

Dr. Austin Smith

PPD

Chief Medical Officer since 2020

Doctor of Medicine from the Royal College of Surgeons in Ireland

David Simmons

PPD

Chief Executive Officer since 2012

Bachelor’s degree in Applied Mathematics and Industrial Management from Carnegie Mellon University

Rho Federal Systems Division, Inc.

Industry Sponsor

Trials

Recruited

15,000+

Published Research Related to This Trial

Intravenous daratumumab, when combined with bortezomib, thalidomide, and dexamethasone, significantly improves treatment outcomes for adults with newly diagnosed multiple myeloma, leading to higher rates of stringent complete response and prolonged progression-free survival, as shown in the phase III CASSIOPEIA trial.

The addition of daratumumab has a minimal impact on overall toxicity, with the most common serious side effects being blood-related issues, indicating it is a relatively safe option for patients undergoing treatment for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma.Lamb, YN.[2021]

Daratumumab, a monoclonal antibody targeting CD38, has shown significant efficacy as a monotherapy in relapsed/refractory multiple myeloma, achieving an overall response in about one-third of patients, with rapid and durable effects.

In combination with other treatments like bortezomib or lenalidomide, daratumumab significantly prolonged progression-free survival, although the overall survival benefit is still being evaluated, and it was generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Relapsed and/or Refractory Multiple Myeloma.Blair, HA.[2018]

In a 6-month trial involving 107 patients with various rheumatic diseases, treatment with biological agents like rituximab and infliximab led to significant improvements, with 57.9% achieving complete remission and 39.3% achieving partial remission.

The incidence of severe adverse events (AEs) was relatively low, with only 5.6% of patients experiencing serious AEs, including severe infusion reactions and systemic infections, indicating that while risks exist, the benefits of using biological agents in managing rheumatic diseases are notable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Severe adverse events from treatment with genetically engineered biological agents in patients with rheumatic diseases].Moiseev, SV., Novikov, PI., Semenkova, EN., et al.[2015]

Citations

1.jnj.comjnj.com/media-center/press-releases/darzalex-faspro-daratumumab-and-hyaluronidase-fihj-shows-51-percent-reduction-in-risk-of-progression-to-active-multiple-myeloma-for-patients-with-high-risk-smoldering-multiple-myeloma

DARZALEX FASPRO® (daratumumab and hyaluronidase ...Additionally, patients who received DARZALEX FASPRO® saw a higher overall response rate of 63.4 percent compared to 2.0 percent with active ...

2.darzalexhcp.comdarzalexhcp.com/

DARZALEX® (daratumumab) & DARZALEX FASPRO ...You can see from the results presented that more patients achieved a complete response or better with DRd by 18 months vs Rd alone. Forty-nine point eight ...

3.pmc.ncbi.nlm.nih.govpmc.ncbi.nlm.nih.gov/articles/PMC10758190/

Safety and Efficacy of Subcutaneous Daratumumab in ...At median follow-up of 7.5 months, progression of disease had been observed in 51% of patients in each arm. Median progression-free survival was ...

4.prnewswire.comprnewswire.com/news-releases/tecvayli-plus-darzalex-faspro-combination-regimen-significantly-improves-progression-free-survival-and-overall-survival-versus-standard-of-care-302585407.html

TECVAYLI® plus DARZALEX FASPRO® combination ...At almost three years follow-up, the combination of TECVAYLI and DARZALEX FASPRO met the primary endpoint of progression-free survival (PFS) ( ...

5.jnjmedicalconnect.comjnjmedicalconnect.com/products/darzalex-faspro/medical-content/darzalex-darzalex-faspro-adverse-event-hematologic-events-in-patients-with-relapsed-and-refractor

DARZALEX + DARZALEX FASPRO - Adverse EventThe most common grade 3/4 (≥20%) hematologic TEAEs were neutropenia (41.5%), anemia (27.7%), and thrombocytopenia (24.6%).

6.accessdata.fda.govaccessdata.fda.gov/drugsatfda_docs/label/2021/761145s009lbl.pdf

Darzalex Faspro - accessdata.fda.govFatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO [see. Adverse Reactions (6.3)]. Systemic Reactions. In a ...

7.clinicaltrials.govclinicaltrials.gov/study/NCT05671757

Study Details | NCT05671757 | Daratumumab in Primary ...The purpose of this study is to see if the study medication, daratumumab, is safe to treat individuals with Anti-Phospholipid Syndrome (APS).

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