- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04610320
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
Completed
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
8
Phase
- 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
- Name: Stacy Kobayashi
- Phone Number: 650-723-2805
- Email: stacyk@stanford.edu
Study Locations
-
-
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
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 |
Intervention / Treatment |
---|---|
Experimental: Daratumumab-SC Injection
|
>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
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
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
Investigators
- 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)
July 1, 2021
Primary Completion (Actual)
January 26, 2024
Study Completion (Actual)
January 26, 2024
Study Registration Dates
First Submitted
October 26, 2020
First Submitted That Met QC Criteria
October 26, 2020
First Posted (Actual)
October 30, 2020
Study Record Updates
Last Update Posted (Actual)
March 25, 2024
Last Update Submitted That Met QC Criteria
March 21, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID 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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