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

6 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a drug combination called daratumumab/hyaluronidase-fihj (DARZALEX Faspro™) to help people waiting for a heart transplant who have high levels of HLA antibodies. The drug works by targeting specific immune cells to lower these antibodies, making it easier to find a compatible donor and reducing the risk of transplant rejection.

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.

How is the drug Daratumumab different from other treatments for heart transplant rejection?

Daratumumab is unique because it targets CD38, a protein on the surface of certain immune cells, which may help reduce antibody-mediated rejection in heart transplant patients. This mechanism is different from other treatments like bortezomib, which targets plasma cells to reduce donor-specific antibodies. ^{1 2 3 4 5}

Research Team

Barry Boilson, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

References

1. United States pubmed.ncbi.nlm.nih.gov

Rapid reduction in donor-specific anti-human leukocyte antigen antibodies and reversal of antibody-mediated rejection with bortezomib in pediatric heart transplant patients. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Induction therapy after cardiac transplantation: a comparison of anti-thymocyte globulin and daclizumab in the prevention of acute rejection. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Increased negative impact of donor HLA-specific together with non-HLA-specific antibodies on graft outcome. [2023]

4. Denmark pubmed.ncbi.nlm.nih.gov

Reduction of HLA donor specific antibodies in heart transplant patients treated with proteasome inhibitors for antibody mediated rejection. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Bortezomib-containing regimen for primary treatment of early antibody-mediated cardiac allograft rejection: a case report. [2015]