Daratumumab-SC for Highly Sensitized Patients Awaiting Heart Transplantation

March 21, 2024 updated by: Ronald Witteles

A Phase 1 Study of Daratumumab-SC for Reduction of Circulating Antibodies in Patients With High Allosensitization Awaiting Heart Transplantation

The purpose of this study is to test whether Daratumumab-SC, a drug that eliminates antibody-producing plasma cells, can effectively lower the level of preformed antibodies in patients awaiting heart transplantation. These preformed antibodies limit the number of donor hearts that are compatible for the patients. If Daratumumab-SC can effectively remove preformed, donor-specific antibodies, then highly allosensitized patients will have more compatible hearts available to them, potentially decreasing transplant waitlist time and reducing mortality.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
8

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94304
        • Stanford Health Care

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.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participant is on an active list for a heart transplant.
  • Participant has a high level of allosensitization, defined as a calculated PRA (panel of reactive antibodies) of 50%, based on their antibody status at the time of entry into the study.
  • Ability to understand and willingness to sign an informed consent form prior to any study-related procedures.
  • Women of childbearing potential must have a negative pregnancy test at screening.
  • Both male and female patients must use effective methods of birth control, must not donate eggs or sperm during the course of the study and for 3 months after stopping daratumumab-SC.
  • Adequate bone marrow function.
  • Adequate renal function (estimated GFR greater than or equal to 15 mL/min by the Cockcroft-Gault formula).

Exclusion Criteria:

  • History of allergy or intolerance to daratumumab or Daratumumab-SC.
  • Prior diagnosis of myeloma or light chain amyloidosis.
  • Active infection.
  • Women who are pregnant or breastfeeding.

  • Ongoing desensitization treatment with another agent. Subjects are excluded if they have received:

    • a. IVIG within 30 days of enrollment.
    • b. Proteasome inhibitor within 60 days of enrollment.
    • c. Rituximab within 180 days of enrollment.
  • Any condition which could interfere with, or the treatment for which might interfere with, the conduct of the study or which would, in the opinion of the Investigator, unacceptably increase the subject's risk by participating in the study.
  • Contraindication to herpes zoster prophylaxis.
  • Known to be seropositive for human immunodeficiency virus (HIV).
  • Known to be seropositive 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.
  • Known to be 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).
  • Known 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 subjects suspected of having COPD and subjects must be excluded if FEV1 is <50% of predicted normal.
  • Known moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification.
  • Known history of human immunodeficiency virus (HIV).
  • History of blood product transfusion within 60 days of enrollment, or anticipated need for blood product transfusion during the course of the study.
  • Moderate-severe liver dysfunction.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Daratumumab-SC Injection
  • Participants will receive a subcutaneous dose of Daratumumab-SC (1800 mg) weekly for 8 doses and then every other week for 2 doses.
  • Participants will undergo laboratory testing, including for circulating antibodies, at baseline, prior to each infusion session, and at the end of the study.
Drug: Daratumumab-SC
>Daratumumab-SC 1800 mg subcutaneous weekly for 8 doses and then every other week for 2 doses.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in the level of preformed HLA antibodies before and after Daratumumab-SC treatment, based on the absolute difference in PRA levels before and after treatment.
Time Frame: Baseline and Week 12 (or the last measurement prior to heart transplantation, whichever is earlier).
Will assess the difference in PRA percentage (defined based on those HLA antibodies which have a mean fluorescence intensity [MFI] >3000) at baseline versus Week 12.
Baseline and Week 12 (or the last measurement prior to heart transplantation, whichever is earlier).

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percent MFI change for each individual preformed HLA antibody at Week 6.
Time Frame: Baseline and Week 6 (or the last measurement prior to heart transplantation, whichever is earlier).
Will measure the percent change in the MFI of each circulating preformed HLA antibody from baseline to Week 6 or the time of heart transplantation (whichever is earlier).
Baseline and Week 6 (or the last measurement prior to heart transplantation, whichever is earlier).
Percent MFI change for each individual preformed HLA antibody at Week 12.
Time Frame: Baseline and Week 12 (or the last measurement prior to heart transplantation, whichever is earlier).
Will measure the percent change in the MFI of each circulating preformed HLA antibody from baseline to Week 12 or the time of heart transplantation (whichever is earlier).
Baseline and Week 12 (or the last measurement prior to heart transplantation, whichever is earlier).
Percent MFI change for each individual preformed HLA antibody at Week 15.
Time Frame: Baseline and Week 15 (or the last measurement prior to heart transplantation, whichever is earlier).
Will measure the percent change in the MFI of each circulating preformed HLA antibody from baseline to Week 15 or the time of heart transplantation (whichever is earlier).
Baseline and Week 15 (or the last measurement prior to heart transplantation, whichever is earlier).
Change in the level of preformed HLA antibodies before and after Daratumumab-SC treatment, based on the absolute difference in PRA levels at baseline and Week 6.
Time Frame: Baseline and Week 6 (or the last measurement prior to heart transplantation, whichever is earlier).
Will assess the difference in PRA percentage (defined based on those HLA antibodies which have a mean fluorescence intensity [MFI] >3000) at baseline versus Week 6.
Baseline and Week 6 (or the last measurement prior to heart transplantation, whichever is earlier).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ronald Witteles

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ronald M Witteles, MD, Stanford University

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 Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 26, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 26, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 26, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 26, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 30, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 21, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 53476

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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