Kidney Transplant Recipients
Conditions
Keywords
COVID-19 vaccine, SARS-CoV-2 antibody response
Brief summary
Antibodies are an important part of the body's defense against infection. Individuals who have no antibodies or very low antibody levels are considered less well protected from Coronavirus Disease 2019 (COVID-19) than those who have higher antibody levels. What level of antibodies is necessary for protection is currently unknown. Inadequate antibody response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination has been described among kidney transplant recipients. The aim of this study is to elicit an antibody response to vaccination against SARS-CoV-2 in kidney transplant recipients who have failed to respond to two doses of either the Moderna COVID-19 vaccine or Pfizer-BioNTech Coronavirus Disease 2019 (COVID-19) vaccine.
Detailed description
This is an open label, non-randomized study in kidney transplant recipients who received two doses of either mRNA COVID-19 vaccine and have a negative (\<0.8 U/mL) or low (titer \<50 U/mL) SARS-CoV-2 antibody response using the Roche Elecsys® anti-RBD assay. Eligible participants will receive a third dose of the same mRNA vaccine as the prior two doses.
Interventions
BIOLOGICALBNT162b2 vaccine (Pfizer/BioNTech)
30 microgram dose
BIOLOGICALmRNA-1273 vaccine (Moderna)
100 microgram dose
Sponsors
PPD Development, LP
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Open label, non-randomized.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Individuals who meet all the following criteria are eligible for enrollment as study participants- 1. Able to understand and provide informed consent; 2. Recipient of kidney transplant ≥12 months prior to enrollment, without treated allograft rejection in the 6 months preceding enrollment; 3. Received 2 doses of either the Moderna COVID-19 vaccine or Pfizer-BioNTech COVID-19 vaccine as specified in the respective Food and Drug Administration Emergency Use Authorization (FDA EUAs), \>30 days and \<8 months prior to enrollment ; and, 4. Negative (antibody titer \< 0.8U/mL) or low (antibodies detected at titer ≤ 50 U/mL) response to the vaccine at \> 30 days from dose 2 of the Moderna COVID-19 vaccine or the Pfizer BioNTech vaccine, using the Roche Elecsys® anti-Receptor Binding Domain (RBD) assay.
Exclusion criteria
Individuals who meet any of these criteria are not eligible for enrollment as study participants- 1. Recipient of any number of doses of any COVID vaccine product other than the Moderna COVID-19 vaccine or the Pfizer-BioNTech COVID-19 vaccine; 2. Known history of severe allergic reaction to any component of either the Moderna COVID-19 vaccine or Pfizer-BioNTech COVID-19 vaccine; 3. Thrombotic events, myocarditis, or pericarditis temporally associated with prior dose of COVID-19 vaccine; 4. Any change in transplant immunosuppression regimen (drug or dose) in response to suspected or proven rejection within the last 6 months; 5. Significant graft dysfunction; 6. Receipt of any cellular depleting agent (e.g. ATG, Rituximab, Alemtuzumab, Cyclophosphamide) within 12 months preceding enrollment; 7. Receiving systemic immunomodulatory medication(s) for any condition other than transplant; 8. Any untreated active infection, including BK viremia \>10\^4 copies; 9. Infection with human immunodeficiency virus (HIV); 10. Maintenance immunosuppressive regimen that includes belatacept or abatacept; 11. Recent (within one year) or ongoing treatment for malignancy; or 12. Any past or current medical problems, treatments, or findings which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the candidate's ability to comply with study requirements or may impact the quality or interpretation of the data obtained from the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Recipients Who Achieve an Antibody Response >50 U/mL After the Third Dose of mRNA COVID-19 Vaccine | Outcome was measured at 30 days after study intervention (dose 3 vaccination) | The proportion of participants who achieve an antibody response \>50 U/mL after the third dose of vaccine using the Roche Elecsys® anti-RBD assay is considered to show positive response to the intervention, negative response otherwise. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of/Proportion of Participants With Any Serious Adverse Events (SAEs) Following the Third Dose of an mRNA Vaccine | Through Day 30 Post-Vaccination (Dose 3) | Safety measure status post third dose of mRNA vaccine |
| Proportion of Participants Treated for Acute Cell-Mediated and/or Antibody-Mediated Allograft Rejection (Clinical or Biopsy Proven) | Through Day 60 Post-Vaccination (Dose 3) | Safety measure status post third dose of mRNA vaccine |
| Frequency of/Proportion of Participants With Vaccine Reactogenicity (Local or Systemic) and/or Allergy to the mRNA-Based COVID-19 Vaccine | Through Day 7 Post-Vaccination (Dose 3) | Safety measure status post third dose of mRNA vaccine |
| Proportion of Participants With Graft Loss | Through Day 60 Post-Vaccination (Dose 3) | Safety measure status post third dose of mRNA vaccine. |
| Occurrence of Death Among Participants | Through Day 60 Post-Vaccination (Dose 3) | Safety measure status post third dose of mRNA vaccine. |
| Proportion of Participants Who Develop de Novo Donor-Specific Anti-Human Leukocyte Antigens (HLA) Antibody | Through Day 90 Post-Vaccination (Dose 3) | Safety measure status post third dose of mRNA vaccine |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anti-RBD Negative or Low at Study Entry recipients who have failed to respond to two doses of either the Moderna COVID-19 vaccine or Pfizer-BioNTech COVID-19 vaccine. | 81 |
| Total | 81 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Physician decision due to both medical and non-medical considerations | 1 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Anti-RBD Negative or Low at Study Entry |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 44 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants |
| Age, Continuous | 62.9 years STANDARD_DEVIATION 12.6 |
| Antibody response after 2-dose series of mRNA COVID-19 vaccine Anti-RBD low | 42 Participants |
| Antibody response after 2-dose series of mRNA COVID-19 vaccine Anti-RBD negative | 39 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 79 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 49 Participants |
| Region of Enrollment United States | 81 participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 81 |
| other Total, other adverse events | 57 / 81 |
| serious Total, serious adverse events | 12 / 81 |
Outcome results
Primary
Proportion of Recipients Who Achieve an Antibody Response >50 U/mL After the Third Dose of mRNA COVID-19 Vaccine
The proportion of participants who achieve an antibody response \>50 U/mL after the third dose of vaccine using the Roche Elecsys® anti-RBD assay is considered to show positive response to the intervention, negative response otherwise.
Time frame: Outcome was measured at 30 days after study intervention (dose 3 vaccination)
Population: All individuals who receive the intervention and have antibody response measured at 30 days after the intervention will be included in the analysis of the primary outcome. For secondary and exploratory outcomes, all individuals who receive the intervention and have that outcome measured will be included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anti-RBD Negative or Low at Study Entry | Proportion of Recipients Who Achieve an Antibody Response >50 U/mL After the Third Dose of mRNA COVID-19 Vaccine | 69.1 Percentage of participants with response |
Secondary
Frequency of/Proportion of Participants With Any Serious Adverse Events (SAEs) Following the Third Dose of an mRNA Vaccine
Safety measure status post third dose of mRNA vaccine
Time frame: Through Day 30 Post-Vaccination (Dose 3)
Population: The SAE that occurred through Day 30 post-vaccination (dose 3) was a Urinary Tract Infection that was assessed as unrelated to the study vaccine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anti-RBD Negative or Low at Study Entry | Frequency of/Proportion of Participants With Any Serious Adverse Events (SAEs) Following the Third Dose of an mRNA Vaccine | 1.23 Proportion of participants as percentage |
Secondary
Frequency of/Proportion of Participants With Vaccine Reactogenicity (Local or Systemic) and/or Allergy to the mRNA-Based COVID-19 Vaccine
Safety measure status post third dose of mRNA vaccine
Time frame: Through Day 7 Post-Vaccination (Dose 3)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anti-RBD Negative or Low at Study Entry | Frequency of/Proportion of Participants With Vaccine Reactogenicity (Local or Systemic) and/or Allergy to the mRNA-Based COVID-19 Vaccine | Overall Events | 50.6 Proportion of participants as percentage |
| Anti-RBD Negative or Low at Study Entry | Frequency of/Proportion of Participants With Vaccine Reactogenicity (Local or Systemic) and/or Allergy to the mRNA-Based COVID-19 Vaccine | Local Reactogenicity | 45.7 Proportion of participants as percentage |
| Anti-RBD Negative or Low at Study Entry | Frequency of/Proportion of Participants With Vaccine Reactogenicity (Local or Systemic) and/or Allergy to the mRNA-Based COVID-19 Vaccine | Systemic Reactogenicity | 27.2 Proportion of participants as percentage |
| Anti-RBD Negative or Low at Study Entry | Frequency of/Proportion of Participants With Vaccine Reactogenicity (Local or Systemic) and/or Allergy to the mRNA-Based COVID-19 Vaccine | Allergic Reaction | 1.23 Proportion of participants as percentage |
Secondary
Occurrence of Death Among Participants
Safety measure status post third dose of mRNA vaccine.
Time frame: Through Day 60 Post-Vaccination (Dose 3)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anti-RBD Negative or Low at Study Entry | Occurrence of Death Among Participants | 0 Proportion of participants as percentage |
Secondary
Proportion of Participants Treated for Acute Cell-Mediated and/or Antibody-Mediated Allograft Rejection (Clinical or Biopsy Proven)
Safety measure status post third dose of mRNA vaccine
Time frame: Through Day 60 Post-Vaccination (Dose 3)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anti-RBD Negative or Low at Study Entry | Proportion of Participants Treated for Acute Cell-Mediated and/or Antibody-Mediated Allograft Rejection (Clinical or Biopsy Proven) | 0 Proportion of participants as percentage |
Secondary
Proportion of Participants Who Develop de Novo Donor-Specific Anti-Human Leukocyte Antigens (HLA) Antibody
Safety measure status post third dose of mRNA vaccine
Time frame: Through Day 90 Post-Vaccination (Dose 3)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anti-RBD Negative or Low at Study Entry | Proportion of Participants Who Develop de Novo Donor-Specific Anti-Human Leukocyte Antigens (HLA) Antibody | 0 Proportion of participants as percentage |
Secondary
Proportion of Participants With Graft Loss
Safety measure status post third dose of mRNA vaccine.
Time frame: Through Day 60 Post-Vaccination (Dose 3)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anti-RBD Negative or Low at Study Entry | Proportion of Participants With Graft Loss | 0 Proportion of participants as percentage |