Immunosuppression, Lung Transplant Recipient, SARS-CoV-2
Conditions
Keywords
SARS-CoV-2, lung transplant recipient, immunosuppression
Brief summary
Lung transplant recipients have poor outcomes after COVID-19 infection with mortality. Due to the immunosuppression, they have had poor responses to SARS-CoV-2 vaccine and remain at high risk of poor outcomes. This is a Phase I/II clinical trial to evaluate the safety and immune response from a higher dose mRNA-1273 vaccine among lung transplant recipients who have already received three or four doses of the COVID-19 vaccine.
Detailed description
This is a Phase I/II open-label dose-finding trial among lung transplant recipients who received three or four mRNA vaccine doses (mRNA-1273 or BNT162b2) after lung transplantation to: standard-dose (50 ug), mid-dose (100 ug) or high-dose (200 ug) mRNA-1273 booster vaccine. Sixty participants will be enrolled into three dose groups: 1) Standard-dose - 20 participants, 2) Mid-dose - 20 participants, 3) High-dose - 20 participants. The first 2 participants in both the mid-dose and high dose groups will be considered the 'sentinel' group. Participants in the sentinel group will receive the vaccine and undergo a 7-day observation period for safety and reactogenicity before additional participants are enrolled into that dose group. Overall study enrollment will begin with the mid-dose sentinel group (n=2). During the observation period for the mid-dose sentinel group, we will enroll two participants into the standard-dose group. Once the mid-dose sentinel group completes their 7-day observation period without triggering halting rules and is approved to proceed by the DSMB, we will enroll the next 27 participants (Cohort 1) with a 2:1 randomization into the mid-dose (n=18) and standard-dose (n=9) groups. Once all 20 participants have received their mid-dose vaccine without triggering halting rules and is approved to proceed by the DSMB, we will enroll the high-dose sentinel group (n=2). Once the high-dose sentinel group completes their 7-day observation period without triggering halting rules and is approved to proceed by the DSMB, we will enroll the next 27 participants (Cohort 2) with a 2:1 randomization into the high-dose (n=18) and standard-dose (n=9) groups. All 20 participants in the mid-dose group will be enrolled prior to the enrollment of the high-dose group. We will perform stratified randomization for the two cohorts based on: 1) the number of prior doses, and 2) prior receipt of any BNT162b2 vaccines. Randomization with be done by the UCLA Clinical and Translational Science Institute (CTSI) statistics team based on scheduled participants prior to the study visit. The 6 participants in the sentinel (n=4) and initial (n=2) groups (Table 1) will be assigned into the 3 groups based on their scheduled visit day.
Interventions
Study Drug will be administered via intramuscular injection (IM). Only one dose of study drug will be administered for the study.
Sponsors
ModernaTX, Inc.
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Groups will be enrolled as follows: 1. Mid-dose - Sentinel group, n=2 2. Standard-dose - Initial group, n=2 3. Cohort 1: 2:1 Randomization into * Mid-dose group, n=18 * Standard-dose group, n=9 4. High-dose - Sentinel group, n=2 5. Cohort 2: 2:1 Randomization into * High-dose group, n=18 * Standard-dose group, n=9 We will perform stratified randomization for the two cohorts based on: 1) the number of prior doses, and 2) prior receipt of any BNT162b2 vaccines.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. All adult lung transplant recipients (age ≥ 18 at the time of consent) who received all of their COVID-19 vaccines after lung transplantation. 2. Received three or four doses of either the Moderna mRNA-1273 or Pfizer BNT162b2 vaccine with the last dose received at least 4 months prior to study enrollment. 3. Currently receiving standard regimen of three drug immunosuppression with prednisone, tacrolimus and mycophenolate mofetil (cellcept, minimum 250 mg bid) or mycophenolate sodium (myfortic, minimum 180 mg bid). 4. Agrees not to receive other investigational agents for prophylaxis against COVID-19 including Evusheld monoclonal antibodies for at least 30 days after the study vaccine. 5. Understands and agrees to comply with the study procedures and provides written informed consent. 6. Is in stable health without any new or worsening medical conditions in the opinion of the Investigator. 7. Female participants of childbearing potential (\<1 year since start of menopause) may be enrolled in the study if the participant fulfills all the following criteria: 1. Has a negative pregnancy test at Visit 1 Day 1. 2. Has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first injection (Day 1). 3. Has agreed to continue adequate contraception or practice abstinence through 3 months following the booster injection (Day 90). 4. Is not currently breastfeeding. 5. Adequate female contraception is defined as consistent and correct use of a Food and Drug Administration (FDA) approved contraceptive method in accordance with the product label. For example: i. Barrier method (such as condoms, diaphragm, or cervical cap) used in conjunction with spermicide ii. Intrauterine device iii. Prescription hormonal contraceptive taken or administered via oral (pill), transdermal (patch), subdermal, or IM route iv. Sterilization of a female participant's monogamous male partner prior to entry into the study v. Note: periodic abstinence (e.g., calendar, ovulation methods) and withdrawal are not acceptable methods of contraception.
Exclusion criteria
1. Previous documented COVID-19 infection. 2. Use of investigational agents for prophylaxis against COVID-19 within 90 days of the start of the study, including Evusheld monoclonal antibodies. 3. Ongoing therapy for acute cellular or antibody mediated rejection. 4. Intravenous immunoglobulins (IVIG) administration within the prior 3 months or ongoing IVIG therapy. 5. Anaphylaxis or allergic reaction to any prior vaccines. 6. History of anaphylaxis or other significant adverse reaction requiring medical intervention after receipt of a vaccine. 7. Is acutely ill or febrile 24 hours prior to or at the Day 1 visit. Fever is defined as a body temperature ≥ 38.0°C/100.4°F. Participants meeting this criterion may be rescheduled within the relevant window periods. Afebrile participants with minor illnesses can be enrolled at the discretion of the investigator. 8. Pregnant or breastfeeding. 9. Has a medical, psychiatric, or occupational condition that may pose additional risk as a result of participation, or that could interfere with safety assessments or interpretation of results according to the investigator's judgment. 10. Known history of hypertension (HTN) with systolic blood pressure (BP) \> 180 mm Hg at the Day 1 visit. 11. Known history of hypotension with systolic blood pressure \< 85 mm Hg at the Day 1 visit. 12. Bleeding disorder considered a contraindication to IM injection or phlebotomy. 13. Active malignancy diagnosed within previous 4 years (excluding non-melanoma skin cancer). 14. Received a major surgery including lung transplantation in the past 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Day 1 - Day 7 after study drug administration | Solicited local and systemic reactogenicity adverse events were documented daily in a dedicated diary, and assigned a grade 1-3 according to the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA grading scale). Higher grades are assigned to more severe events. |
| Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Day 1 - Day 30 after study drug administration | Comprehensive recording of occurrence and severity grade of unsolicited adverse events (AEs) daily. These events were documented in a dedicated diary starting from Day 1 of the study and continued through to Day 30. Data collection encompassed adverse events not specifically solicited, with each event's frequency recorded for analysis. |
| Participants Reporting Any Serious Adverse Experiences (SAEs) and Adverse Events of Special Interests (AESIs) Related to the Intervention From Day 1 Until Day 180. | Day 1 - Day 180 after study drug administration | This comprehensive data collection is intended to provide insights into the occurrence of significant adverse events and specific adverse events of interest over an extended period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Humoral Immunogenicity Measured by Anti-RBD and Anti-spike (S-2P) IgG Levels at Day 30. | Day 30 after study drug administration | This evaluation provides insights into the vaccine's ability to induce an immune response by quantifying specific antibody levels targeting key viral components, contributing to the understanding of vaccine efficacy and immune response dynamics. |
| Cellular Immunogenicity (CD4+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 1, Day 30 after study drug administration | Percent of total CD4+ T Cells to quantify vaccine-induced cellular immune response, the activation and functionality of specific immune cell populations to contribute to understanding the vaccine's ability to elicit a robust cellular immune response, which is essential for effective protection against viral infections. |
| Humoral Immunogenicity Measured by Neutralizing Antibody Titers From a Pseudovirus Neutralization Assay at Day 30. | Day 1, Day 30 after study drug administration | Provide a direct measure of the vaccine-induced immune response's ability to neutralize viral infection, offering critical insights into vaccine efficacy and immune response effectiveness |
| Cellular Immunogenicity (CD8+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 1, Day 30 after study drug administration | Percent of total CD8+ T Cells to quantify vaccine-induced cellular immune response, the activation and functionality of specific immune cell populations to contribute to understanding the vaccine's ability to elicit a robust cellular immune response, which is essential for effective protection against viral infections. |
Countries
United States
Participant flow
Pre-assignment details
High Dose arm was not recorded because no participants enrolled in this group.
Participants by arm
| Arm | Count |
|---|---|
| Standard-dose - Initial Group 50 ug ) mRNA-1273 booster vaccine | 8 |
| Mid-dose - Sentinel Group 100 ug ) mRNA-1273 booster vaccine | 11 |
| High-dose - Sentinel Group 200 ug ) mRNA-1273 booster vaccine | 0 |
| Total | 19 |
Baseline characteristics
| Characteristic | Standard-dose - Initial Group | Mid-dose - Sentinel Group | High-dose - Sentinel Group | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 5 Participants | 0 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 0 Participants | 12 Participants |
| Count of Participants | 8 Participants | 11 Participants | 0 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 0 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 8 Participants | 0 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 0 Participants | 6 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 0 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 11 |
| other Total, other adverse events | 5 / 8 | 10 / 11 |
| serious Total, serious adverse events | 1 / 8 | 2 / 11 |
Outcome results
Primary
Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR)
Solicited local and systemic reactogenicity adverse events were documented daily in a dedicated diary, and assigned a grade 1-3 according to the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA grading scale). Higher grades are assigned to more severe events.
Time frame: Day 1 - Day 7 after study drug administration
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard-dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Injection site swelling, Grade 2 | 0 participants |
| Standard-dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Headache - Grade 1 | 2 participants |
| Standard-dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Injection site pain -Grade 2 | 2 participants |
| Standard-dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Headache - Grade 2 | 1 participants |
| Standard-dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Any Systemic AR | 3 participants |
| Standard-dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Headache - Grade 3 | 1 participants |
| Standard-dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Injection site pain -Grade 1 | 4 participants |
| Standard-dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Myalgia - Grade 1 | 1 participants |
| Standard-dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Fatigue - grade 1 | 1 participants |
| Standard-dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Arthralgia - Grade 1 | 1 participants |
| Standard-dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Injection Site Swelling-Grade 1 | 0 participants |
| Standard-dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Fatigue - Grade 2 | 2 participants |
| Standard-dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Nausea/Vomiting - Grade 1 | 1 participants |
| Standard-dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Any Local AR | 5 participants |
| Standard-dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Nausea/Vomiting - Grade 2 | 1 participants |
| Standard-dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Fatigue - Grade 3 | 1 participants |
| Standard-dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Nausea/Vomiting - Grade 3 | 1 participants |
| Standard-dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Chills - Grade 1 | 0 participants |
| Mid-Dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Nausea/Vomiting - Grade 3 | 0 participants |
| Mid-Dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Any Local AR | 9 participants |
| Mid-Dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Injection site pain -Grade 1 | 7 participants |
| Mid-Dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Injection site pain -Grade 2 | 4 participants |
| Mid-Dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Injection Site Swelling-Grade 1 | 1 participants |
| Mid-Dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Injection site swelling, Grade 2 | 1 participants |
| Mid-Dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Any Systemic AR | 3 participants |
| Mid-Dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Fatigue - grade 1 | 1 participants |
| Mid-Dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Fatigue - Grade 2 | 1 participants |
| Mid-Dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Fatigue - Grade 3 | 1 participants |
| Mid-Dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Headache - Grade 1 | 2 participants |
| Mid-Dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Headache - Grade 2 | 1 participants |
| Mid-Dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Headache - Grade 3 | 0 participants |
| Mid-Dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Myalgia - Grade 1 | 1 participants |
| Mid-Dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Arthralgia - Grade 1 | 0 participants |
| Mid-Dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Chills - Grade 1 | 1 participants |
| Mid-Dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Nausea/Vomiting - Grade 1 | 0 participants |
| Mid-Dose | Participants Experiencing Solicited Local and Systemic Reactogenicity Adverse Reactions (AR) | Nausea/Vomiting - Grade 2 | 0 participants |
Primary
Participants Reporting Any Serious Adverse Experiences (SAEs) and Adverse Events of Special Interests (AESIs) Related to the Intervention From Day 1 Until Day 180.
This comprehensive data collection is intended to provide insights into the occurrence of significant adverse events and specific adverse events of interest over an extended period
Time frame: Day 1 - Day 180 after study drug administration
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard-dose | Participants Reporting Any Serious Adverse Experiences (SAEs) and Adverse Events of Special Interests (AESIs) Related to the Intervention From Day 1 Until Day 180. | 0 Participants |
| Mid-Dose | Participants Reporting Any Serious Adverse Experiences (SAEs) and Adverse Events of Special Interests (AESIs) Related to the Intervention From Day 1 Until Day 180. | 0 Participants |
Primary
Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary
Comprehensive recording of occurrence and severity grade of unsolicited adverse events (AEs) daily. These events were documented in a dedicated diary starting from Day 1 of the study and continued through to Day 30. Data collection encompassed adverse events not specifically solicited, with each event's frequency recorded for analysis.
Time frame: Day 1 - Day 30 after study drug administration
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard-dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Any unsolicited AE | 1 Participants |
| Standard-dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Pain in extremity - left foot, Moderate | 0 Participants |
| Standard-dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Pain in extremity - bilateral shoulder pain, Mild | 0 Participants |
| Standard-dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Fatigue, Mild | 0 Participants |
| Standard-dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Fatigue, Moderate | 0 Participants |
| Standard-dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Hyperkalemia, Moderate | 0 Participants |
| Standard-dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Creatinine increased, Mild | 0 Participants |
| Standard-dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | COVID-19 infection - Mild | 1 Participants |
| Standard-dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | COVID-19 infection - Moderate | 0 Participants |
| Standard-dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Joint irritation of left foot and left hand, Mild | 0 Participants |
| Standard-dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Dyspnea, Mild | 0 Participants |
| Standard-dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Palpitations, Mild | 0 Participants |
| Standard-dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | LE edema, Mild | 0 Participants |
| Standard-dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Mitral regurgitation worsening, Severe | 0 Participants |
| Standard-dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Chest heaviness, Mild | 1 Participants |
| Standard-dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Shortness of breath worsening, Mild | 1 Participants |
| Standard-dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Chest discomfort worsening, Mild | 1 Participants |
| Standard-dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Lightheadedness, Mild | 0 Participants |
| Standard-dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Mechanical trip and fall, Moderate | 0 Participants |
| Standard-dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Left flank pain, Moderate | 0 Participants |
| Standard-dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Dry cough, Moderate | 0 Participants |
| Mid-Dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Dyspnea, Mild | 1 Participants |
| Mid-Dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Any unsolicited AE | 7 Participants |
| Mid-Dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Mechanical trip and fall, Moderate | 1 Participants |
| Mid-Dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Pain in extremity - left foot, Moderate | 1 Participants |
| Mid-Dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Palpitations, Mild | 1 Participants |
| Mid-Dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Pain in extremity - bilateral shoulder pain, Mild | 1 Participants |
| Mid-Dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Chest discomfort worsening, Mild | 0 Participants |
| Mid-Dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Fatigue, Mild | 1 Participants |
| Mid-Dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | LE edema, Mild | 1 Participants |
| Mid-Dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Fatigue, Moderate | 1 Participants |
| Mid-Dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Dry cough, Moderate | 1 Participants |
| Mid-Dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Hyperkalemia, Moderate | 1 Participants |
| Mid-Dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Mitral regurgitation worsening, Severe | 1 Participants |
| Mid-Dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Creatinine increased, Mild | 1 Participants |
| Mid-Dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Lightheadedness, Mild | 1 Participants |
| Mid-Dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | COVID-19 infection - Mild | 2 Participants |
| Mid-Dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Chest heaviness, Mild | 0 Participants |
| Mid-Dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | COVID-19 infection - Moderate | 3 Participants |
| Mid-Dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Left flank pain, Moderate | 1 Participants |
| Mid-Dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Joint irritation of left foot and left hand, Mild | 1 Participants |
| Mid-Dose | Participants Reporting Unsolicited Adverse Events (AEs) Recorded on a Daily Diary | Shortness of breath worsening, Mild | 0 Participants |
Secondary
Cellular Immunogenicity (CD4+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining.
Percent of total CD4+ T Cells to quantify vaccine-induced cellular immune response, the activation and functionality of specific immune cell populations to contribute to understanding the vaccine's ability to elicit a robust cellular immune response, which is essential for effective protection against viral infections.
Time frame: Day 1, Day 30 after study drug administration
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard-dose | Cellular Immunogenicity (CD4+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 30-TNFα | 0.15 percent of total CD4+ T Cells detectable |
| Standard-dose | Cellular Immunogenicity (CD4+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 1-IFNγ | 0.01 percent of total CD4+ T Cells detectable |
| Standard-dose | Cellular Immunogenicity (CD4+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 30-IFNγ | 0.04 percent of total CD4+ T Cells detectable |
| Standard-dose | Cellular Immunogenicity (CD4+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 1-IL-2 | 0.01 percent of total CD4+ T Cells detectable |
| Standard-dose | Cellular Immunogenicity (CD4+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 30-IL-2 | 0.05 percent of total CD4+ T Cells detectable |
| Standard-dose | Cellular Immunogenicity (CD4+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 1-TNFα | 0.03 percent of total CD4+ T Cells detectable |
| Standard-dose | Cellular Immunogenicity (CD4+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 1- IFNγ, IL-2, or TNFα | 0.01 percent of total CD4+ T Cells detectable |
| Standard-dose | Cellular Immunogenicity (CD4+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 30-IFNγ, IL-2, or TNFα | 0.23 percent of total CD4+ T Cells detectable |
| Mid-Dose | Cellular Immunogenicity (CD4+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 30-IFNγ, IL-2, or TNFα | 0.01 percent of total CD4+ T Cells detectable |
| Mid-Dose | Cellular Immunogenicity (CD4+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 30-TNFα | 0.01 percent of total CD4+ T Cells detectable |
| Mid-Dose | Cellular Immunogenicity (CD4+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 30-IL-2 | 0.20 percent of total CD4+ T Cells detectable |
| Mid-Dose | Cellular Immunogenicity (CD4+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 1-IFNγ | 0.01 percent of total CD4+ T Cells detectable |
| Mid-Dose | Cellular Immunogenicity (CD4+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 1- IFNγ, IL-2, or TNFα | 0.01 percent of total CD4+ T Cells detectable |
| Mid-Dose | Cellular Immunogenicity (CD4+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 30-IFNγ | 0.02 percent of total CD4+ T Cells detectable |
| Mid-Dose | Cellular Immunogenicity (CD4+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 1-TNFα | 0.01 percent of total CD4+ T Cells detectable |
| Mid-Dose | Cellular Immunogenicity (CD4+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 1-IL-2 | 0.07 percent of total CD4+ T Cells detectable |
Secondary
Cellular Immunogenicity (CD8+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining.
Percent of total CD8+ T Cells to quantify vaccine-induced cellular immune response, the activation and functionality of specific immune cell populations to contribute to understanding the vaccine's ability to elicit a robust cellular immune response, which is essential for effective protection against viral infections.
Time frame: Day 1, Day 30 after study drug administration
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard-dose | Cellular Immunogenicity (CD8+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 1-IFNγ | 0.01 percent of total CD8+ T Cells detectable |
| Standard-dose | Cellular Immunogenicity (CD8+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 30-IFNγ | 0.04 percent of total CD8+ T Cells detectable |
| Standard-dose | Cellular Immunogenicity (CD8+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 1-IL-2 | 0.01 percent of total CD8+ T Cells detectable |
| Standard-dose | Cellular Immunogenicity (CD8+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 30-IL-2 | 0.01 percent of total CD8+ T Cells detectable |
| Standard-dose | Cellular Immunogenicity (CD8+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 1-TNFα | 0.01 percent of total CD8+ T Cells detectable |
| Standard-dose | Cellular Immunogenicity (CD8+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 30-TNFα | 0.01 percent of total CD8+ T Cells detectable |
| Standard-dose | Cellular Immunogenicity (CD8+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 1- IFNγ, IL-2, or TNFα | 0.01 percent of total CD8+ T Cells detectable |
| Standard-dose | Cellular Immunogenicity (CD8+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 30-IFNγ, IL-2, or TNFα | 0.01 percent of total CD8+ T Cells detectable |
| Mid-Dose | Cellular Immunogenicity (CD8+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 30-IFNγ, IL-2, or TNFα | 0.01 percent of total CD8+ T Cells detectable |
| Mid-Dose | Cellular Immunogenicity (CD8+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 1-IFNγ | 0.01 percent of total CD8+ T Cells detectable |
| Mid-Dose | Cellular Immunogenicity (CD8+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 1-TNFα | 0.01 percent of total CD8+ T Cells detectable |
| Mid-Dose | Cellular Immunogenicity (CD8+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 30-IFNγ | 0.01 percent of total CD8+ T Cells detectable |
| Mid-Dose | Cellular Immunogenicity (CD8+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 1- IFNγ, IL-2, or TNFα | 0.01 percent of total CD8+ T Cells detectable |
| Mid-Dose | Cellular Immunogenicity (CD8+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 1-IL-2 | 0.01 percent of total CD8+ T Cells detectable |
| Mid-Dose | Cellular Immunogenicity (CD8+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 30-TNFα | 0.01 percent of total CD8+ T Cells detectable |
| Mid-Dose | Cellular Immunogenicity (CD8+ T Cell Responses After Spike Protein Peptide Pool Stimulation) Measured by Cellular Response Assays Including Flow Cytometry With Intracellular Staining. | Day 30-IL-2 | 0.01 percent of total CD8+ T Cells detectable |
Secondary
Humoral Immunogenicity Measured by Anti-RBD and Anti-spike (S-2P) IgG Levels at Day 30.
This evaluation provides insights into the vaccine's ability to induce an immune response by quantifying specific antibody levels targeting key viral components, contributing to the understanding of vaccine efficacy and immune response dynamics.
Time frame: Day 30 after study drug administration
Population: We did not run the assay described. The humoral immunogenicity was measured as neutralizing antibodies since the COVID immunogenicity field had progressed and binding antibodies were not being reported in the literature (only the neutralizing antibodies for the most part).
Secondary
Humoral Immunogenicity Measured by Neutralizing Antibody Titers From a Pseudovirus Neutralization Assay at Day 30.
Provide a direct measure of the vaccine-induced immune response's ability to neutralize viral infection, offering critical insights into vaccine efficacy and immune response effectiveness
Time frame: Day 1, Day 30 after study drug administration
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard-dose | Humoral Immunogenicity Measured by Neutralizing Antibody Titers From a Pseudovirus Neutralization Assay at Day 30. | Neutralizing antibody titre - Day 1 | 4260 Titer |
| Standard-dose | Humoral Immunogenicity Measured by Neutralizing Antibody Titers From a Pseudovirus Neutralization Assay at Day 30. | Neutralizing antibody titre - Day 30 | 5436 Titer |
| Mid-Dose | Humoral Immunogenicity Measured by Neutralizing Antibody Titers From a Pseudovirus Neutralization Assay at Day 30. | Neutralizing antibody titre - Day 1 | 6514 Titer |
| Mid-Dose | Humoral Immunogenicity Measured by Neutralizing Antibody Titers From a Pseudovirus Neutralization Assay at Day 30. | Neutralizing antibody titre - Day 30 | 5293 Titer |