Clinical trial NCT04952402: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Covid19
SARS-CoV2 Infection
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2021-07-07
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Neutralizing Antibody (NAb) Level
timeFrame: Measured 140 days after the first dose of the vaccine
Secondary outcomes:
measure: Geometric Mean of Relative Change in Neutralizing Antibody Levels From Pre-vaccine to Post-vaccine
timeFrame: Measured before the first dose of the vaccine, and 56 days after the first dose of the vaccine
measure: Proportion of Participants With New Grade 3 or Higher AE, or SAE, or AE Leading to Change or Discontinuation in Vaccine Receipt
timeFrame: From first dose of the vaccine through 140 days after the first dose of the vaccine
measure: Number of Participants With Grade 1 or Higher Allergic Reaction
timeFrame: From first dose of the vaccine through 56 days after the first dose of the vaccine
measure: Proportion of Participants With Grade 2 or Higher Injection Site Reaction
timeFrame: From first dose of the vaccine through 56 days after the first dose of the vaccine
measure: Geometric Mean of Relative Change in Neutralizing Antibody Levels From Pre-vaccine to Post-vaccine by Received Vaccine
timeFrame: Measured before the first dose of the vaccine, and 56 days after the first dose of the vaccine
Other outcomes:
measure: CD4+ T Cell Response to SARS-CoV-2 Spike Protein
timeFrame: At the visit 56 days after the first dose of the vaccine
measure: CD8+ T Cell Response to SARS-CoV-2 Spike Protein
timeFrame: At the visit 56 days after the first dose of the vaccine
measure: IgG Serologic Response to SARS-CoV-2 Spike Protein at Receptor Binding Domain (RBD) and N Terminal Domain (NTD) and Matrix (M) Protein.
timeFrame: At the visit 56 days after the first dose of the vaccine
measure: Flow Cytometry of PBMC for Markers of Exhaustion on B and T Cells
timeFrame: At study entry/Day 0 and 56 days after the first vaccine dose.
measure: IgM Serologic Response to SARS-CoV-2 Spike Protein at Receptor Binding Domain (RBD) and N Terminal Domain (NTD) and Matrix (M) Protein.
timeFrame: At the visit 56 days after the first dose of the vaccine
Locations:
city: Los Angeles
country: United States
facility: UCLA CARE Center CRS
state: California
city: San Diego
country: United States
facility: UCSD Antiviral Research Center CRS
state: California
city: Chicago
country: United States
facility: Rush University CRS (Site ID: 2702)
state: Illinois
city: Boston
country: United States
facility: Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS
state: Massachusetts
city: Chapel Hill
country: United States
facility: Chapel Hill CRS (Site ID: 3201)
state: North Carolina
city: Seattle
country: United States
facility: University of Washington AIDS CRS
state: Washington
Study officials:
affiliation: UCSD Antiviral Research Center
name: David Smith, MD, MAS
role: STUDY_CHAIR
References: