Back to resultsSARS-CoV-2 Immune Responses After COVID-19 Therapy and Subsequent Vaccine
Primary Purpose
Covid19, SARS-CoV2 Infection
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Study-provided Moderna mRNA-1273 COVID-19 vaccine
Community-provided Moderna mRNA-1273 COVID-19 Vaccine
Community-Provided Pfizer-BioNTech BNT162b2 COVID-19 Vaccine
Sponsored by
About this trial
This is an interventional prevention trial for Covid19
Eligibility Criteria
Inclusion Criteria:
- For all participants: Ability and willingness of participant (or legally authorized representative) to provide informed consent prior to initiation of any study procedures.
- For all participants: Individuals ≥18 years of age
- For participants who are in, or who have completed, the ACTIV-2/A5401 trial: Receipt of all selected investigational therapy or active comparator/placebo for that therapy at selected sites.
- For participants who are in, or who have completed, the ACTIV-2/A5401 trial and will be receiving study-provided Moderna mRNA-1273 COVID-19 vaccine: Receipt of the last dose of investigational therapy or active comparator/placebo for that therapy ≥60 days and ≤240 days prior to study entry.
- For participants who are in, or who have completed, the ACTIV-2/A5401 trial and will be receiving community-provided mRNA-based COVID-19 vaccine: Receipt of the last dose of investigational therapy or active comparator/placebo for that therapy ≥60 and ≤240 days prior to planned receipt of the first dose of community-provided vaccine.
Exclusion Criteria:
- For participants who are in, or who have completed, the ACTIV-2/A5401 trial: Self-report of prior receipt of a non-mRNA-based COVID-19 vaccine
- For participants who are in, or who have completed, the ACTIV-2/A5401 trial: Self-report of receipt of the second dose of an mRNA-based COVID-19 vaccine.
- For participants who are in, or who have completed, the ACTIV-2/A5401 trial: Self-report of a second SARS-CoV-2 infection after the infection that qualified the participant for ACTIV-2/A5401.
- For non-A5401/ACTIV-2 participants: Self-report of receipt of any prior COVID-19 vaccine.
- For non-A5401/ACTIV-2 participants: Known prior history of any SARS-CoV-2-positive test (e.g., PCR test, Nucleic Acid Amplification Test (NAAT), antigen test, serology test).
- For participants who will receive study-provided Moderna mRNA-1273 COVID-19 vaccine: Known allergy to any component of the Moderna COVID-19 vaccine.
Sites / Locations
- UCLA CARE Center CRS
- UCSD Antiviral Research Center CRS
- Rush University CRS (Site ID: 2702)
- Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS
- Chapel Hill CRS (Site ID: 3201)
- University of Washington AIDS CRS
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort: ACTIV-2/A5401
Cohort: COVID-19 Naïve
Arm Description
Participants of the ACTIV-2/A5401 randomized trial who received a select investigational (active) therapy (AZD7442 IM or IV, BRII-196 + BRII 198 IV, SAB 185 (3,840 or 10,240 units/kg) IV, BMS 096414+BMS 986413 subcutaneous, Camostat Oral) or its corresponding comparator (Placebo).
Participants without known history of prior SARS-CoV-2 infection defined as no known history of any SARS-CoV-2 positive test (non-ACTIV-2/A5401 participants).
Outcomes
Primary Outcome Measures
Neutralizing Antibody (NAb) Level
NAb level was measured by using both 50% neutralizing dilution titers (ND50) and 80% neutralizing titers (ND80). A higher NAb level corresponds to a stronger immune response. For ND50 values less than lower limit of quantification (LLQ), we impute with 10 (which is ½ LLQ of 20). For ND50 values exceeding the upper limit of quantification (ULQ), we impute with 20,000 (a value suggested by the immunology lab, which is 2 times the ULQ of 10,000). For ND80, we impute similarly with 10 and 20,000. We carry forward the Day 56 NAb measurement if the Day 140 measurement is not reported.
Secondary Outcome Measures
Geometric Mean of Relative Change in Neutralizing Antibody Levels From Pre-vaccine to Post-vaccine
Relative change is defined as the ratio of post-vaccine NAb level/pre-vaccine NAb level. A ratio greater than one indicates an increase of NAb response. For ND50 values less than lower limit of quantification (LLQ), we impute with 10 (which is ½ LLQ of 20). For ND50 values exceeding the upper limit of quantification (ULQ), we impute with 20,000 (a value suggested by the immunology lab, which is 2 times the ULQ of 10,000). For ND80, we impute similarly with 10 and 20,000.
Proportion of Participants With New Grade 3 or Higher AE, or SAE, or AE Leading to Change or Discontinuation in Vaccine Receipt
An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. A serious adverse event (SAE) is defined as any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the other outcomes listed in the definition above.
Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1).
Number of Participants With Grade 1 or Higher Allergic Reaction
Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1).
Proportion of Participants With Grade 2 or Higher Injection Site Reaction
Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1).
Geometric Mean of Relative Change in Neutralizing Antibody Levels From Pre-vaccine to Post-vaccine by Received Vaccine
Relative change is defined as the ratio of post-vaccine NAb level/pre-vaccine NAb level by received vaccine, i.e., Moderna mRNA-1273 versus Pfizer-BioNTech BNT162b2. A ratio greater than one indicates an increase of NAb response for those on Moderna mRNA-1273 versus Pfizer-BioNTech BNT162b2. For ND50 values less than lower limit of quantification (LLQ), we impute with 10 (which is ½ LLQ of 20). For ND50 values exceeding the upper limit of quantification (ULQ), we impute with 20,000 (a value suggested by the immunology lab, which is 2 times the ULQ of 10,000). For ND80, we impute similarly with 10 and 20,000.
Full Information
NCT ID
NCT04952402
First Posted
June 28, 2021
Last Updated
May 22, 2023
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
1. Study Identification
Unique Protocol Identification Number
NCT04952402
Brief Title
SARS-CoV-2 Immune Responses After COVID-19 Therapy and Subsequent Vaccine
Official Title
SARS-CoV-2 Immune Responses After COVID-19 Therapy and Subsequent Vaccine
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
July 9, 2021 (Actual)
Primary Completion Date
February 28, 2022 (Actual)
Study Completion Date
January 10, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety and efficacy of mRNA COVID-19 vaccines in:
• People with prior COVID-19 (SARS-CoV-2 infection) who were in the ACTIV-2/A5401 study.
And
• People who have never had COVID-19 (SARS-CoV-2 infection).
Detailed Description
A5404 is a phase IV, open-label study. The objective of A5404 is to evaluate how prior investigational therapy for COVID-19 versus comparator (placebo or active comparator) affects vaccine response. The safety of mRNA COVID-19 vaccines is also explored.
Eligible A5404 participants include: Participants of ACTIV-2/A5401 at selected sites who received an investigational therapy or its comparator; and persons without known history of prior SARS-CoV-2 infection defined as no known history of any SARS-CoV-2 positive test (non-A5401 participants). In line with our protocol, for outcome measures related to neutralizing antibodies and adverse events, we further break down the ACTIV-2/A5401 participants into two exposure groups: those who received an active therapy (AZD7442 IM or IV, BRII-196 + BRII 198 IV, SAB 185 (3,840 or 10,240 units/kg) IV, BMS 096414+BMS 986413 subcutaneous) and those who received Camostat Oral or Placebo.
Participants of ACTIV-2/A5401 received study-provided standard dosing of the Moderna mRNA-1273 vaccine, or a community-provided mRNA-based COVID-19 vaccine (e.g., Moderna or Pfizer). Participants in ACTIV-2/A5401 received their mRNA-based COVID-19 vaccine 60-240 days after receiving their last dose of a select ACTIV-2/A5401 investigational therapy, or its comparator. Participants without prior COVID-19 received study-provided standard dosing of the Moderna mRNA-1273 vaccine.
The study closed early to accrual on February 25, 2022 due to slow enrollment. Clarification Memo #1 (dated January 11, 2023) reflects decisions to discontinue follow up at study Day 365 instead of following participants to Day 730 after the first dose of vaccine and to reallocate some secondary outcome measures to exploratory outcome measures.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19, SARS-CoV2 Infection
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
43 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort: ACTIV-2/A5401
Arm Type
Experimental
Arm Description
Participants of the ACTIV-2/A5401 randomized trial who received a select investigational (active) therapy (AZD7442 IM or IV, BRII-196 + BRII 198 IV, SAB 185 (3,840 or 10,240 units/kg) IV, BMS 096414+BMS 986413 subcutaneous, Camostat Oral) or its corresponding comparator (Placebo).
Arm Title
Cohort: COVID-19 Naïve
Arm Type
Experimental
Arm Description
Participants without known history of prior SARS-CoV-2 infection defined as no known history of any SARS-CoV-2 positive test (non-ACTIV-2/A5401 participants).
Intervention Type
Biological
Intervention Name(s)
Study-provided Moderna mRNA-1273 COVID-19 vaccine
Intervention Description
Participants received a two-dose series (100 µg (0.5 mL) was administered intramuscularly (IM) at Day 0 and Day 28).
Intervention Type
Biological
Intervention Name(s)
Community-provided Moderna mRNA-1273 COVID-19 Vaccine
Intervention Description
Participants received a two-dose series.
Intervention Type
Biological
Intervention Name(s)
Community-Provided Pfizer-BioNTech BNT162b2 COVID-19 Vaccine
Intervention Description
Participants received a two-dose series.
Primary Outcome Measure Information:
Title
Neutralizing Antibody (NAb) Level
Description
NAb level was measured by using both 50% neutralizing dilution titers (ND50) and 80% neutralizing titers (ND80). A higher NAb level corresponds to a stronger immune response. For ND50 values less than lower limit of quantification (LLQ), we impute with 10 (which is ½ LLQ of 20). For ND50 values exceeding the upper limit of quantification (ULQ), we impute with 20,000 (a value suggested by the immunology lab, which is 2 times the ULQ of 10,000). For ND80, we impute similarly with 10 and 20,000. We carry forward the Day 56 NAb measurement if the Day 140 measurement is not reported.
Time Frame
Measured 140 days after the first dose of the vaccine
Secondary Outcome Measure Information:
Title
Geometric Mean of Relative Change in Neutralizing Antibody Levels From Pre-vaccine to Post-vaccine
Description
Relative change is defined as the ratio of post-vaccine NAb level/pre-vaccine NAb level. A ratio greater than one indicates an increase of NAb response. For ND50 values less than lower limit of quantification (LLQ), we impute with 10 (which is ½ LLQ of 20). For ND50 values exceeding the upper limit of quantification (ULQ), we impute with 20,000 (a value suggested by the immunology lab, which is 2 times the ULQ of 10,000). For ND80, we impute similarly with 10 and 20,000.
Time Frame
Measured before the first dose of the vaccine, and 56 days after the first dose of the vaccine
Title
Proportion of Participants With New Grade 3 or Higher AE, or SAE, or AE Leading to Change or Discontinuation in Vaccine Receipt
Description
An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. A serious adverse event (SAE) is defined as any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the other outcomes listed in the definition above.
Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1).
Time Frame
From first dose of the vaccine through 140 days after the first dose of the vaccine
Title
Number of Participants With Grade 1 or Higher Allergic Reaction
Description
Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1).
Time Frame
From first dose of the vaccine through 56 days after the first dose of the vaccine
Title
Proportion of Participants With Grade 2 or Higher Injection Site Reaction
Description
Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1).
Time Frame
From first dose of the vaccine through 56 days after the first dose of the vaccine
Title
Geometric Mean of Relative Change in Neutralizing Antibody Levels From Pre-vaccine to Post-vaccine by Received Vaccine
Description
Relative change is defined as the ratio of post-vaccine NAb level/pre-vaccine NAb level by received vaccine, i.e., Moderna mRNA-1273 versus Pfizer-BioNTech BNT162b2. A ratio greater than one indicates an increase of NAb response for those on Moderna mRNA-1273 versus Pfizer-BioNTech BNT162b2. For ND50 values less than lower limit of quantification (LLQ), we impute with 10 (which is ½ LLQ of 20). For ND50 values exceeding the upper limit of quantification (ULQ), we impute with 20,000 (a value suggested by the immunology lab, which is 2 times the ULQ of 10,000). For ND80, we impute similarly with 10 and 20,000.
Time Frame
Measured before the first dose of the vaccine, and 56 days after the first dose of the vaccine
Other Pre-specified Outcome Measures:
Title
CD4+ T Cell Response to SARS-CoV-2 Spike Protein
Description
Team re-prioritized the analysis of secondary objectives due to limited accrual and moved this outcome to exploratory.
Time Frame
At the visit 56 days after the first dose of the vaccine
Title
CD8+ T Cell Response to SARS-CoV-2 Spike Protein
Description
Team re-prioritized the analysis of secondary objectives due to limited accrual and moved this outcome to exploratory.
Time Frame
At the visit 56 days after the first dose of the vaccine
Title
IgG Serologic Response to SARS-CoV-2 Spike Protein at Receptor Binding Domain (RBD) and N Terminal Domain (NTD) and Matrix (M) Protein.
Description
Team re-prioritized the analysis of secondary objectives due to limited accrual and moved this outcome to exploratory.
Time Frame
At the visit 56 days after the first dose of the vaccine
Title
Flow Cytometry of PBMC for Markers of Exhaustion on B and T Cells
Description
Team re-prioritized the analysis of secondary objectives due to limited accrual and moved this outcome to exploratory.
Time Frame
At study entry/Day 0 and 56 days after the first vaccine dose.
Title
IgM Serologic Response to SARS-CoV-2 Spike Protein at Receptor Binding Domain (RBD) and N Terminal Domain (NTD) and Matrix (M) Protein.
Description
Team re-prioritized the analysis of secondary objectives due to limited accrual and moved this outcome to exploratory.
Time Frame
At the visit 56 days after the first dose of the vaccine
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
For all participants: Ability and willingness of participant (or legally authorized representative) to provide informed consent prior to initiation of any study procedures.
For participants who are in, or who have completed, the ACTIV-2/A5401 trial: Receipt of all selected investigational therapy or active comparator/placebo for that therapy at selected sites.
For participants who are in, or who have completed, the ACTIV-2/A5401 trial and receive study-provided Moderna mRNA-1273 COVID-19 vaccine: Receipt of the last dose of investigational therapy or active comparator/placebo for that therapy ≥30 days and ≤240 days prior to study entry.
For participants who are in, or who have completed, the ACTIV-2/A5401 trial and have received or will be receiving community-provided mRNA-based COVID-19 vaccine: Receipt of the last dose of investigational therapy or active comparator/placebo for that therapy ≥30 and ≤240 days prior to receipt or planned receipt of the first dose of community-provided vaccine.
Exclusion Criteria:
For participants who are in, or who have completed, the ACTIV-2/A5401 trial: Self-report of prior receipt of a non-mRNA-based COVID-19 vaccine.
For participants who are in, or who have completed, the ACTIV-2/A5401 trial: Self-report of receipt of the first dose of an mRNA-based COVID-19 vaccine 140 days or more before A5404 enrollment.
For participants who are in, or who have completed, the ACTIV-2/A5401 trial: Self-report of a second SARS-CoV-2 infection after the infection that qualified the participant for ACTIV-2/A5401.
For non-A5401/ACTIV-2 participants: Self-report of receipt of any prior COVID-19 vaccine.
For non-A5401/ACTIV-2 participants: Known prior history of any SARS-CoV-2-positive test (e.g., PCR test, Nucleic Acid Amplification Test (NAAT), antigen test, serology test).
For participants who receive study-provided Moderna mRNA-1273 COVID-19 vaccine: Known allergy to any component of the Moderna COVID-19 vaccine.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Smith, MD, MAS
Organizational Affiliation
UCSD Antiviral Research Center
Official's Role
Study Chair
Facility Information:
Facility Name
UCLA CARE Center CRS
City
Los Angeles
State/Province
California
ZIP/Postal Code
90035-4709
Country
United States
Facility Name
UCSD Antiviral Research Center CRS
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Rush University CRS (Site ID: 2702)
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Chapel Hill CRS (Site ID: 3201)
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
University of Washington AIDS CRS
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104-9929
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data that underlie results in the publication, after deidentification.
IPD Sharing Time Frame
Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
IPD Sharing Access Criteria
With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group.
For what types of analyses? To achieve aims in the proposal approved by the AIDS Clinical Trials Group.
By what mechanism will data be made available? Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://actgnetwork.org/submit-a-proposal/. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.
Links:
URL
https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables
Description
The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017.
URL
https://rsc.niaid.nih.gov/clinical-research-sites/manual-expedited-reporting-adverse-events-daids
Description
Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010
Learn more about this trial
SARS-CoV-2 Immune Responses After COVID-19 Therapy and Subsequent Vaccine
We'll reach out to this number within 24 hrs