Vaccination for Recovered Inpatients With COVID-19 (VATICO)

Study Overview
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Brief Summary
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In this Phase 4, open-label trial, participants of the ACTIV-3/TICO clinical trial (NCT04501978) at selected study sites who receive certain pre-specified, blinded investigational agents or placebo as part of that trial and who have since achieved sustained recovery from COVID-19 and meet certain criteria, including not having received a COVID-19 vaccination since enrollment, will be randomized to one of four groups to receive the Moderna mRNA-1273 or the Pfizer BNT162b2 vaccine (mRNA vaccines). No dummy/placebo vaccine will be used. Choice of Moderna or Pfizer vaccine is determined based on availability at the site. The choice is individual, although participants vaccinated twice should receive the same type of vaccine when receiving two injections. The study's objective is to evaluate if the vaccine is best administered early or deferred after recovery, and whether one injection provides comparable immune response to a two injection course of vaccination. Participants will remain blinded to the interventions received in the ACTIV-3/TICO study, however allocation to the timing of vaccination and to one or two vaccinations in this (VATICO) study is not blinded.

Detailed Description
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Participants from the ACTIV-3/TICO clinical trial must still be blinded and be within 28 to 90 days after their initial TICO randomization. They will be randomized as part of a 2x2 factorial design to one of four groups: (i) Immediate versus 12 week deferral of first dose administration, and also (ii) One dose only, versus two doses to be given 4 weeks apart. The primary objectives of this study are: (i) To estimate the difference in neutralizing antibody (NAb) response to the mRNA vaccine from baseline to Week 48 among participants vaccinated early versus deferred, and (ii) To estimate the difference in NAb response to this vaccine among participants vaccinated once versus twice. A key secondary objective is to ascertain the effect, if any, of SARS-CoV-2 monoclonal antibodies, and other interventions that have been studied in hospitalized COVID-19 subjects, on natural and vaccine-induced immunity. Participants will be offered enrollment between 28 and 90 days after receiving select ACTIV-3/TICO investigational agents or placebo. Participants will have blood collected at time of enrollment, and at Weeks 12, 24 and 48 after study entry. Approximately 640 participants will be recruited. The total sample size will depend on how many investigational agents/placebo are evaluated in ACTIV-3/TICO.

Official Title
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SARS-CoV-2 Vaccination Strategies in Previously Hospitalized and Recovered COVID-19 Patients

Conditions
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Covid19

Intervention / Treatment
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* Biological: Moderna mRNA-1273 COVID-19 vaccine
* Biological: Pfizer BNT162b2 COVID-19 vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participating in (ACTIV-3) TICO trial and received a selected blinded investigational agent, or placebo for that agent, at selected sites. Willingness to strictly adhere to the randomly allocated dosage number and schedule for vaccine administration. Participant is between Day 28 and Day 90 TICO visits inclusive at time of randomization. At time of screening for this study, has experienced sustained recovery for at least two consecutive weeks, i.e. having return uninterrupted to the person's premorbid living facility (or equivalent) for at least 2 consecutive weeks. Ability and willingness of participant (or legally authorized representative) to provide informed consent prior to initiation of any study procedures. Exclusion Criteria: Receipt of a SARS-CoV-2 (COVID-19) vaccine after enrollment into TICO. Participants who received a SARS-CoV-2 vaccine prior to enrollment in TICO may be enrolled in this study. Known allergy to any component of the study eligible vaccine(s).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I1<br>Immediate, one dose. Vaccination at study entry | Biological: Moderna mRNA-1273 COVID-19 vaccine<br>* 100 µg intramuscular injection<br>Biological: Pfizer BNT162b2 COVID-19 vaccine<br>* 30 µg intramuscular injection<br>|
| Experimental: Group I2<br>Immediate, two doses. Vaccination at study entry and Week 4 | Biological: Moderna mRNA-1273 COVID-19 vaccine<br>* 100 µg intramuscular injection<br>Biological: Pfizer BNT162b2 COVID-19 vaccine<br>* 30 µg intramuscular injection<br>|
| Experimental: Group D1<br>Deferred, one dose. Vaccination at Week 12 only | Biological: Moderna mRNA-1273 COVID-19 vaccine<br>* 100 µg intramuscular injection<br>Biological: Pfizer BNT162b2 COVID-19 vaccine<br>* 30 µg intramuscular injection<br>|
| Experimental: Group D2<br>Deferred, two doses. Vaccination at Week 12 and Week 16 | Biological: Moderna mRNA-1273 COVID-19 vaccine<br>* 100 µg intramuscular injection<br>Biological: Pfizer BNT162b2 COVID-19 vaccine<br>* 30 µg intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neutralizing antibody (NAb) levels following vaccination | Evaluated using the ratio of geometric mean responses | Thru Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody levels 12 weeks after first vaccination | Evaluated using the ratio of geometric mean responses | 12 weeks after first vaccination | 
| Estimated percentage of participants with > 16-fold differences in NAbs | Evaluated using the ratio of geometric mean responses | Baseline and Week 48 | 
| Estimated percentage of participants with > 16-fold differences in NAbs | Evaluated using the ratio of geometric mean responses | Just before vaccination to 12 weeks post-vaccination | 
| Estimated percentage of participants with 8-16-fold differences in NAbs | Evaluated using the ratio of geometric mean responses | Baseline and Week 48 | 
| Estimated percentage of participants with 8-16-fold differences in NAbs | Evaluated using the ratio of geometric mean responses | Just before vaccination to 12 weeks post-vaccination | 
| Estimated percentage of participants with 4-8-fold differences in NAbs | Evaluated using the ratio of geometric mean responses | Baseline and Week 48 | 
| Estimated percentage of participants with 4-8-fold differences in NAbs | Evaluated using the ratio of geometric mean responses | Just before vaccination to 12 weeks post-vaccination | 
| Estimated percentage of participants with 2-4-fold differences in NAbs | Evaluated using the ratio of geometric mean responses | Baseline and Week 48 | 
| Estimated percentage of participants with 2-4-fold differences in NAbs | Evaluated using the ratio of geometric mean responses | Just before vaccination to 12 weeks post-vaccination | 
| Estimated percentage of participants with < 2-fold differences in NAbs | Evaluated using the ratio of geometric mean responses | Baseline and Week 48 | 
| Estimated percentage of participants with < 2-fold differences in NAbs | Evaluated using the ratio of geometric mean responses | Just before vaccination to 12 weeks post-vaccination | 
| Ratio of post-vaccine level/pre-vaccine level | Measured by change in NAb response | Up to Week 24 | 
| Composite number of death, serious adverse event (SAE), grade 3 AEs and grade 4 AEs |  | 12 weeks following first dose | 
| Number of Deaths |  | Thru Week 24 | 
| Number of SAEs |  | Thru Week 24 | 
| Percentage of participants assigned 2nd vaccine dose who do not receive it for any reason |  | Thru Week 48 | 
| Percentage of participants assigned 2nd vaccine dose who do not receive it due to an AE following first dose |  | Thru Week 48 | 
| Incidence of non-adherence to assigned treatment strategy |  | Thru Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, COVID 19, Coronaviridae Infections, Coronavirus Infections, RNA Virus Infections, Virus Diseases, Nidovirales Infections, SARS-CoV-2, SARS Coronavirus, VATICO, ACTIV-3, ACTIV3, TICO