Daratumumab in HLA Desensitization Prior to Transplantation

NCT05300451 | Enrolling By Invitation Phase 2 DMC FDA Drug

• 1 other identifier: 20-012885
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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 Leukocyte Antigen) antibodies in a person waiting for a heart transplant.

Conditions

Cardiac Transplant

Keywords

Sensitisation; HLA

Outcome Measures

Primary Outcomes (2)

• Effect of daratumumab therapy on human leukocyte antibody (HLA) titers in resistant antibody mediated rejection (AMR)

  Levels of HLA titers by measure of fluorescence intensity levels (MFI) of donor specific antibodies (DSA).

  Sixteen weeks

• Effect of daratumumab therapy on HLA antibody titers in sensitization (pre-transplant)

  Assessed as calculated panel of reactive antibodies (cPRA) and absolute HLA antibody levels (MFI)

  Sixteen weeks

Secondary Outcomes (5)

• Effect of daratumumab on cardiac contractility in HLA sensitized patients

  One month post completion

• Effect of daratumumab on Cardiac Systolic Strain in HLA sensitized patients

  One month post completion

• Effect of daratumumab on Left Ventricular Filling Pressure Ratio in HLA sensitized patients

  One month post completion

• Effect of daratumumab on Right Ventricular Systolic Pressure (RVSP) in HLA sensitized patients

  One month post completion

• Effect of daratumumab on incidence of acute CMR post-transplant in sensitized patients

  Time Frame: Weeks 2, 3 and 4 post-transplant

Study Arms (1)

HLA Desensitization Group

EXPERIMENTAL

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

Biological: Daratumumab and hyaluronidase-fihj

Interventions

Daratumumab and hyaluronidase-fihj BIOLOGICAL

Daratumumab and hyaluronidase-fihj for subcutaneous (under the skin) injection has different dosing and administration instructions compared to daratumumab for intravenous (in the vein) infusion. Daratumumab and hyaluronidase-fihj contains recombinant hyaluronidase, which mimics hyaluronidase, a naturally occurring substance that increases permeability of subcutaneous tissue. This makes it possible for 15 mL containing 1,800 mg of daratumumab to be administered in approximately 3 to 5 minutes. Subjects will receive a 1800mg/30000u injection subcutaneously weekly for a total of 8 doses

Also known as: DARZALEX FASPRO®

HLA Desensitization Group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Absolute neutrophil count \> 1,500
• Total bilirubin \< 1.5x institutional upper limit normal (ULN)
• AST/ALT \< 2. 5 - 3x ULN (Options for patients with liver dysfunction may be available)
• Creatinine clearance \> 20 ml/min
• Calculated PRA (cPRA) greater than 50%.
• Currently actively listed for heart or combined heart and kidney transplantation.
• Negative pregnancy test (if woman of childbearing potential) If able to become pregnant or father a child, agreement to use one of the birth control methods described in this protocol
• Able to provide informed consent

You may not qualify if:

• Prior or current exposure to any of the following: daratumumab or other anti-CD-38 therapies, exposure to an investigational drug (including investigational vaccine) or invasive investigational medical device for any indication within 4 weeks or 5 pharmacokinetic half-lives, whichever is longer.
• Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) \< 50% of predicted normal. Note that FEV1 testing is required for participants suspected of having COPD and participants must be excluded if FEV1 is \< 50% of predicted normal.
• Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification. Note that participants who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate.
• Woman who is pregnant or breastfeeding. Participant is: known history of human immunodeficiency virus (HIV); Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Subjects with resolved infection (i.e., subjects who are HBsAg negative with antibodies to total hepatitis B core antigen \[anti-HBc\] with or without the presence of hepatitis B surface antibody \[anti-HBs\]) must be screed using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of HBV vaccination, do not need to be testing for HBV DNA by PCR; Seropositive for hepatitis C (except in the setting of a sustained virologic response \[SVR\], defined as aviremia at least 12 weeks after completion of antiviral therapy).
• Clinically significant cardiac disease, including: myocardial infarction within 6 months before randomization, or unstable or uncontrolled disease/condition related to or affection cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV); Uncontrolled cardiac arrhythmia
• Patients listed for combined heart and liver transplantation will be excluded, as our unique experience with combined heart liver transplant (liver placed first), has demonstrated that in those cases high levels of circulating HLA antibodies may not increase the risk of hyperacute rejection.
• Seropositivity for human immunodeficiency virus (HIV)
• Seropositivity for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-HBc\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
• Seropositivity for hepatitis C (except in the setting of a sustained virologic response \[SVR\], defined as aviremia at least 12 weeks after completion of antiviral therapy).
• Patients unable to give informed consent will also be excluded.

Sponsors & Collaborators

• Barry A. Boilson: lead
• Janssen Biotech, Inc.: collaborator

Study Sites (1)

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Interventions

daratumumab

Study Officials

• Barry Boilson, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 8, 2022
• First Posted: March 29, 2022
• Study Start: March 31, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: October 30, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)