Daratumumab for Heart Transplant Rejection

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Barry A. Boilson

Must not be taking: Anti-CD-38 therapies

Disqualifiers: COPD, Asthma, HIV, Hepatitis B, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how well the drug daratumumab (also known as Darzalex, Darzalex SC, or Darzalex Faspro) reduces high levels of certain antibodies in people awaiting a heart transplant. High antibody levels can complicate transplants, so lowering them might improve outcomes. Individuals actively listed for a heart or combined heart and kidney transplant with high antibody levels might be suitable for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important findings.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that daratumumab, also known as DARZALEX Faspro™, has been tested in many patients, primarily those with multiple myeloma, a type of blood cancer. These studies have generally found the drug to be well-tolerated. Common side effects include low levels of white blood cells (neutropenia), red blood cells (anemia), and platelets (thrombocytopenia). Some patients also experienced infections.

The FDA has approved daratumumab for other uses, indicating that its safety is monitored and considered acceptable for those conditions. However, this study is in an early phase, so researchers are still learning about its safety for people awaiting a heart transplant. Participants in this trial will help provide more information about how well daratumumab is tolerated in this specific situation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for heart transplant rejection, which often involves immunosuppressive drugs like corticosteroids and calcineurin inhibitors, daratumumab offers a novel approach by targeting CD38, a protein found on the surface of certain immune cells. This mechanism allows it to potentially reduce the levels of harmful antibodies that can lead to transplant rejection. Researchers are excited about daratumumab because it could provide a more precise method of desensitization for patients with high levels of Human Leukocyte Antigen (HLA) antibodies, who are at a higher risk of rejection. Additionally, its administration as a subcutaneous injection with hyaluronidase can offer a more convenient and less invasive option compared to traditional treatments.

What evidence suggests that daratumumab might be an effective treatment for heart transplant rejection?

Research has shown that daratumumab, also known as DARZALEX Faspro™, may help lower high levels of HLA antibodies, which can cause heart transplant rejection. In past cases, this treatment successfully managed rejection caused by these antibodies in heart transplants. In this trial, participants in the HLA Desensitization Group will receive daratumumab to target and reduce these antibodies, potentially helping the body accept a new heart more easily. This drug has also effectively treated other conditions, like multiple myeloma, demonstrating its ability to affect immune responses. While more research is needed for heart transplants, early signs suggest it could benefit those with high HLA antibody levels. ^{1 6 7 8 9}

Who Is on the Research Team?

Barry Boilson, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for heart transplant patients or candidates with high HLA antibodies. Participants must have a stable neutrophil count, liver function within certain limits, and adequate kidney function. It's not open to individuals with severe lung conditions like COPD, pregnant or breastfeeding women, those with HIV or hepatitis B/C unless treated successfully, recent major cardiac events, uncontrolled heart issues including arrhythmias, severe asthma in the past 2 years, or prior use of daratumumab.

Inclusion Criteria

Agreement to use one of the birth control methods described in this protocol

Absolute neutrophil count > 1,500

Able to provide informed consent

Exclusion Criteria

I am unable to understand and agree to the study's details.

Living outside the US

Pregnant or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daratumumab/hyaluronidase-fihj 1800mg/30000u subcutaneously once a week for 8 weeks for HLA desensitization

8 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including echocardiograms, heart biopsy or MRI, and blood tests

8 weeks

Several visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab

Trial Overview The study tests DARZALEX Faspro™ (daratumumab/hyaluronidase-fihj) for its effectiveness in reducing HLA antibodies in people awaiting heart transplants and those who've received a transplant but are experiencing antibody mediated rejection due to high levels of these antibodies.

How Is the Trial Designed?

Group I: HLA Desensitization Group Experimental Treatment 1 Intervention

Subjects awaiting cardiac transplantation with high levels of circulating Human Leukocyte Antigen (HLA) antibodies will receive daratumumab/hyaluronidase-fihj.

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

Who Is Running the Clinical Trial?

Barry A. Boilson

Lead Sponsor

Trials

1

Recruited

6+

Janssen Biotech, Inc.

Industry Sponsor

Trials

30

Recruited

18,800+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33617204/

Daratumumab for Antibody-mediated Rejection in Heart ... Daratumumab for Antibody-mediated Rejection in Heart Transplant-A Novel Therapy: Successful Treatment of Antibody-mediated Rejection.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05300451

Study Details | NCT05300451 | Daratumumab in HLA ... The purpose of this study is to learn about how well the drug daratumumab/hyaluronidase-fihj (DARZALEX Faspro™) helps to lower high levels of HLA (Human ...

3. withpower.com withpower.com/trial/phase-2-antibody-mediated-rejection-2-2022-0448d

Daratumumab for Heart Transplant Rejection This trial is testing a drug combination called daratumumab/hyaluronidase-fihj (DARZALEX Faspro™) to help people waiting for a heart transplant who have ...

4. jnjmedicalconnect.com jnjmedicalconnect.com/products/darzalex/medical-content/use-of-darzalex-darzalex-faspro-in-combination-with-carfilzomib-lenalidomide-and-dexamethasone-in-m

DARZALEX® (daratumumab) Efficacy · After induction therapy with D-KRd, 21 (53.8%) patients achieved ≥CR (90% CI, 39.6-67.7; P=0.375), including 16 patients (41%) who ...

5. innovativemedicine.jnj.com innovativemedicine.jnj.com/emea/darzalex-daratumumab-sc-based-regimens-improve-mrd-negativity-and-progression-free-survival-in-newly-diagnosed-multiple-myeloma-and-overall-survival-in-al-amyloidosis

DARZALEX® (daratumumab) SC-based regimens improve ... After a median follow-up of 61.4 months, patients treated with D-VCd showed a 56 percent reduction in the risk of end-stage renal or cardiac ...

6. ema.europa.eu ema.europa.eu/en/documents/product-information/darzalex-epar-product-information_en.pdf

Darzalex, INN - daratumumab - European Medicines Agency Continuous monitoring for this safety signal will be performed in clinical studies and post-marketing safety data. Cardiac disorders and AL amyloidosis-related ...

7. aetna.com aetna.com/cpb/medical/data/900_999/0904.html

Daratumumab (Darzalex) and Daratumumab and ... Darzalex Faspro is indicated for the treatment of adult patients with newly diagnosed light chain amyloidosis in combination with bortezomib, cyclophosphamide ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/761036s044lbl.pdf

Darzalex - accessdata.fda.gov The safety data described below reflects exposure to DARZALEX (16 mg/kg) in 2,459 patients with multiple myeloma including 2,303 patients who received ...

9. jnjmedicalconnect.com jnjmedicalconnect.com/products/darzalex-faspro/medical-content/use-of-darzalex-darzalex-faspro-in-combination-with-carfilzomib-lenalidomide-and-dexamethasone-in-m

DARZALEX FASPRO® (daratumumab and hyaluronidase- ... Grade 3 to 4 D-KRd induction/consolidation-related AEs were neutropenia (39%), anemia (12%), thrombocytopenia (7%), and infection (6%). Derman ...