AllosensitizationPhase 1NCT04610320
Daratumumab-SC for Highly Sensitized Patients Awaiting Heart Transplantation
A Phase 1 study testing Daratumumab-SC in people with Allosensitization and Heart Transplant Failure and Rejection, run by Ronald Witteles at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Allosensitization, Heart Transplant Failure and Rejection
- What is being tested?
- Daratumumab-SC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2021to 26 Jan 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
- Being tested
- Daratumumab-SC
- Keywords
- Immunotherapy, anti-CD38 antibody
- Medical subject headings
- Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Daratumumab-SCDrug
>Daratumumab-SC 1800 mg subcutaneous weekly for 8 doses and then every other week for 2 doses.
| Study group | Role | What they receive |
|---|---|---|
| Daratumumab-SC Injection | Experimental | * 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. Receives: Drug: Daratumumab-SC |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
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.
Measured: Baseline and Week 12 (or the last measurement prior to heart transplantation, whichever is earlier).
Secondary outcomes (4)
Percent MFI change for each individual preformed HLA antibody at Week 6.
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).
Measured: 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.
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).
Measured: 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.
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).
Measured: 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.
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.
Measured: Baseline and Week 6 (or the last measurement prior to heart transplantation, whichever is earlier).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2020
- Study start1 Jul 2021
- Primary completion26 Jan 2024
- Study completion26 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AllosensitizationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ronald Witteles
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Ronald Witteles, Stanford University
- Investigators
- Ronald M Witteles, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04610320
- Sponsor's protocol ID
- 53476
- Status last verified
- Mar 2024
- First submitted
- 26 Oct 2020
- Last updated
- 25 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of Daratumumab-SC for Reduction of Circulating Antibodies in Patients With High Allosensitization Awaiting Heart Transplantation
- ClinicalTrials.gov ID
- NCT04610320
- Acronym / sponsor ID
- 53476
- Keywords
- Immunotherapy, anti-CD38 antibody
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Ronald WittelesUniversity, hospital or other
- Study start
- 1 Jul 2021 (actual)
- Primary completion
- 26 Jan 2024 (actual)
- Study completion
- 26 Jan 2024 (actual)
- First posted
- 30 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Daratumumab-SC Injection | Experimental | Drug: Daratumumab-SC* 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (18 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Daratumumab-SC>Daratumumab-SC 1800 mg subcutaneous weekly for 8 doses and then every other week for 2 doses. | Drug | Daratumumab-SC Injection |
Primary outcome
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.
4 secondary outcomes
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).
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).
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).
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).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ronald M Witteles, MD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Daratumumab-SC in people with Allosensitization and Heart Transplant Failure and Rejection, run by Ronald Witteles at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2024.