SARS-CoV-2 Immune Responses After COVID-19 Therapy and Subsequent Vaccine

NCT04952402 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: A5404
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 6

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).

Conditions

Covid19; SARS-CoV2 Infection

Outcome Measures

Primary Outcomes (1)

• 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.

  Measured 140 days after the first dose of the vaccine

Secondary Outcomes (5)

• Geometric Mean of Relative Change in Neutralizing Antibody Levels From Pre-vaccine to Post-vaccine

  Measured before the first dose of the vaccine, and 56 days after the first dose of the vaccine

• Proportion of Participants With New Grade 3 or Higher AE, or SAE, or AE Leading to Change or Discontinuation in Vaccine Receipt

  From first dose of the vaccine through 140 days after the first dose of the vaccine

• Number of Participants With Grade 1 or Higher Allergic Reaction

  From first dose of the vaccine through 56 days after the first dose of the vaccine

• Proportion of Participants With Grade 2 or Higher Injection Site Reaction

  From first dose of the vaccine through 56 days after the first dose of the vaccine

• Geometric Mean of Relative Change in Neutralizing Antibody Levels From Pre-vaccine to Post-vaccine by Received Vaccine

  Measured before the first dose of the vaccine, and 56 days after the first dose of the vaccine

Other Outcomes (5)

• CD4+ T Cell Response to SARS-CoV-2 Spike Protein

  At the visit 56 days after the first dose of the vaccine

• CD8+ T Cell Response to SARS-CoV-2 Spike Protein

  At the visit 56 days after the first dose of the vaccine

• IgG Serologic Response to SARS-CoV-2 Spike Protein at Receptor Binding Domain (RBD) and N Terminal Domain (NTD) and Matrix (M) Protein.

  At the visit 56 days after the first dose of the vaccine

Study Arms (2)

Cohort: ACTIV-2/A5401

EXPERIMENTAL

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).

Biological: Study-provided Moderna mRNA-1273 COVID-19 vaccine; Biological: Community-provided Moderna mRNA-1273 COVID-19 Vaccine; Biological: Community-Provided Pfizer-BioNTech BNT162b2 COVID-19 Vaccine

Cohort: COVID-19 Naïve

EXPERIMENTAL

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).

Biological: Study-provided Moderna mRNA-1273 COVID-19 vaccine

Interventions

Study-provided Moderna mRNA-1273 COVID-19 vaccine BIOLOGICAL

Participants received a two-dose series (100 µg (0.5 mL) was administered intramuscularly (IM) at Day 0 and Day 28).

Cohort: ACTIV-2/A5401; Cohort: COVID-19 Naïve

Community-provided Moderna mRNA-1273 COVID-19 Vaccine BIOLOGICAL

Participants received a two-dose series.

Cohort: ACTIV-2/A5401

Community-Provided Pfizer-BioNTech BNT162b2 COVID-19 Vaccine BIOLOGICAL

Participants received a two-dose series.

Cohort: ACTIV-2/A5401

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (6)

UCLA CARE Center CRS

Los Angeles, California, 90035-4709, United States

Location

UCSD Antiviral Research Center CRS

San Diego, California, 92103, United States

Location

Rush University CRS (Site ID: 2702)

Chicago, Illinois, 60612, United States

Location

Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS

Boston, Massachusetts, 02115, United States

Location

Chapel Hill CRS (Site ID: 3201)

Chapel Hill, North Carolina, 27599, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 98104-9929, United States

Location

Related Links

• 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.
• Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

The study closed early to accrual due to difficulty enrolling participants. Therefore the sample size is very small and precision is limited.

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company

ACTGCT.gov@fstrf.org

(301) 628-3348

Study Officials

• David Smith, MD, MAS

  UCSD Antiviral Research Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2021
• First Posted: July 7, 2021
• Study Start: July 9, 2021
• Primary Completion: February 28, 2022
• Study Completion: January 10, 2023
• Last Updated: May 24, 2023
• Results First Posted: May 19, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
• 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.

Locations

US (6)