Participants of the ACTIV-3/TICO clinical trial at selected sites who received certain pre-specified blinded investigational agents or placebo as part of that trial, and who have since achieved sustained recovery, and who are still [TICO assignment] blinded, and who are still within 28 to 90 days after initial TICO randomization, will be randomized in this 2x2 factorial design to one of four groups of the Moderna mRNA 1273 or the Pfizer BNT162b2 vaccine (mRNA vaccines) MedDRA version: 23.1 Leve
Conditions
Sponsors
Regents of the University of Minesota
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participating in the TICO trial and received a selected blinded investigational agent or placebo for that agent at selected sites. NOTE: A list of selected investigational agents will be posted on the INSIGHT website. 2. Willingness to strictly adhere to the randomly allocated dosage number and schedule for vaccine administration 3. Participant is between Day 28 and Day 90 TICO visits inclusive at the time of randomization 4. At the time of screening for this protocol, experienced sustained recovery (i.e. the primary endpoint in TICO) for at least two consecutive weeks, i.e. having returned uninterrupted to the person’s premorbid living facility (or equivalent) for at least 2 consecutive weeks 5. Ability and willingness of participant (or legally authorized representative [LAR]) to provide informed consent prior to initiation of any study procedures Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 640 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 300
Exclusion criteria
Exclusion criteria: 1. Receipt of a SARS-CoV-2 (also known as 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 substudy 2. Known allergy to any component of the study eligible vaccine(s)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. Among participants in TICO who were randomized to placebo, to estimate the difference in NAb levels at Week 48 to the Moderna mRNA-1273 vaccine or the Pfizer BNT162b2 vaccine among participants who are vaccinated early (i.e. at time of enrolment into this protocol, within 28 to 90 days of enrolment in TICO) versus deferred (i.e. 12 weeks after enrolment into this protocol). 2. Among participants in TICO who were randomized to placebo, to estimate the difference in neutralizing antibody levels at Week 48 to the Moderna mRNA-1273 vaccine or the Pfizer BNT162b2 vaccine among participants who are vaccinated once versus twice.;Secondary Objective: 1 Estimate difference in NAb response to the Moderna vaccine or the Pfizer vaccine 2 Explore safety of the Moderna or the Pfizer vaccines in persons with prior COVID-19 who did or did not receive prior TICO-defined invest. agents 3 Explore whether the timing of vaccination and/or use of one or two doses affect the safety/tolerability 4 Estimate the percentage in each of the four vaccination groups with differences from baseline to Week 48 5 Compare the one and two-dose vaccination strategies for the percentage of participants who experience a composite outcome of death, SAE, grade 3, grade 4 AEs from vaccination 6 Compare the percentage of who experience death or an SAE through 24 weeks 7 Explore whether host characteristics, co-morbidities, co-medication, the course of prior COVID-19, type of vaccine, interval between enrolment in this protocol and baseline immune status affect humoral responses to SARS-CoV-2 vaccination and kinetics in NAb titers from 12 weeks after vaccination;Primary end point(s): The primary outcome measure is neutralizing antibody levels specific to the Moderna or Pfizer vaccine at Week 48 after randomization. Comparisons will be evaluated using the ratio of geometric mean responses. Antibody levels will be log10 transformed and summarized with stratified analysis of covariance.;Timep | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Antibody levels 12 weeks after the first vaccination (i.e. at Weeks 12 and 24 depending on randomization to vaccinate immediately or deferred). 2. Estimated percentage of participants in each of the four vaccination groups with > 16, 8-16, 4-8, 2-4, and < 2-fold differences in NAbs from baseline to Week 48 and from just before vaccination to 12 weeks thereafter. 3. Relative pre-vaccine to post-vaccine change in NAb response defined as the ratio, post-vaccine level/pre-vaccine level. The pre-vaccine NAb measurement will be obtained immediately before the first dose of the vaccine (i.e. at Week 0 or 12) and the post-vaccine measurement will be obtained at Week 12 or at Week 24, depending on whether the vaccine was administered immediately or deferred. 4. Composite outcome of death, serious adverse event (SAE), grade 3 AEs, and grade 4 AEs within 12 weeks following randomization for the immediate group and from Week 12 to Week 24 in the deferred group. 5. Deaths or SAEs through Week 24. 6. The percentage of participants assigned to 2nd dose who do not receive it: a) for any reason and b) due to an AE following the 1st dose. 7. Non-adherence to the assigned treatment strategy.;Timepoint(s) of evaluation of this end point: As above | — |
Countries
Denmark, Georgia, Nigeria, Peru, Singapore, Spain, Sweden, Uganda, Ukraine, United Kingdom, United States
Contacts
Public ContactJens Lundgren
CHIP - Rigshospitalet, University of Copenhagen
Outcome results
None listed