- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04088903
Study of Daratumumab for Decreasing Circulating Antibodies in Sensitized Patients Awaiting Heart Transplantation
October 26, 2020 updated by: Ronald Witteles
A Phase 1 Study of Daratumumab for Reduction of Circulating Antibodies in Patients With High Allosensitization Awaiting Heart Transplantation
The purpose of this study is to test whether daratumumab, 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 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
Withdrawn
Intervention / Treatment
Study Type
Interventional
Phase
- Phase 1
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
16 years to 73 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
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.
Exclusion Criteria:
- History of allergy or intolerance to daratumumab.
- 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.
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 infusion
|
>Daratumumab 16 mg/kg intravenous weekly for 8 weeks 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 number of individual preformed HLA antibodies before and after daratumumab treatment.
Time Frame: Baseline and Week 12 (or the last measurement prior to heart transplantation, whichever is earlier).
|
Will compare the number of individual circulating preformed human leukocyte antigen (HLA) antibodies (i.e., those HLA antibodies that have a mean fluorescence intensity [MFI] >3000) at baseline with the number of preformed antibodies after daratumumab treatment.
|
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 after 4 weeks of daratumumab treatment.
Time Frame: Baseline and Week 4 (or the last measurement prior to heart transplantation, whichever is earlier).
|
Percent change in the MFI of each circulating preformed HLA antibody from baseline to 4 weeks or the time of heart transplantation (whichever is earlier).
|
Baseline and Week 4 (or the last measurement prior to heart transplantation, whichever is earlier).
|
Percent MFI change for each individual preformed HLA antibody at 8 weeks of daratumumab treatment.
Time Frame: Baseline and Week 8 (or the last measurement prior to heart transplantation, whichever is earlier).
|
Percent change in the MFI of each circulating preformed HLA antibody from baseline to 8 weeks or the time of heart transplantation (whichever is earlier).
|
Baseline and Week 8 (or the last measurement prior to heart transplantation, whichever is earlier).
|
Change in the number of individual preformed HLA antibodies after 6 weeks of daratumumab.
Time Frame: Baseline and Week 6 (or the last measurement prior to heart transplantation, whichever is earlier).
|
Will compare the number of individual circulating preformed HLA antibodies at baseline with the number of preformed antibodies after 6 weeks of daratumumab treatment.
|
Baseline and Week 6 (or the last measurement prior to heart transplantation, whichever is earlier).
|
Change in the percentage of calculated panel of reactive antibodies before and after daratumumab treatment.
Time Frame: Baseline and Week 12 (or the last measurement prior to heart transplantation, whichever is earlier).
|
Will compare the serum panel of reactive antibodies (PRA) percentage at baseline with the PRA percentage after 12 weeks of treatment with daratumumab.
|
Baseline and Week 12 (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 (Anticipated)
April 1, 2021
Primary Completion (Anticipated)
April 1, 2023
Study Completion (Anticipated)
April 1, 2023
Study Registration Dates
First Submitted
September 11, 2019
First Submitted That Met QC Criteria
September 11, 2019
First Posted (Actual)
September 13, 2019
Study Record Updates
Last Update Posted (Actual)
October 28, 2020
Last Update Submitted That Met QC Criteria
October 26, 2020
Last Verified
October 1, 2020
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB-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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