Vaccination for Recovered Inpatients With COVID-19 (VATICO)

Sponsor

International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04969250

Collaborator

University of Minnesota (Other), National Institute of Allergy and Infectious Diseases (NIAID) (NIH), University of Copenhagen (Other), Kirby Institute (Other), Washington D.C. Veterans Affairs Medical Center (U.S. Fed), AIDS Clinical Trials Group (Other), National Heart, Lung, and Blood Institute (NHLBI) (NIH), US Department of Veterans Affairs (U.S. Fed), Prevention and Early Treatment of Acute Lung Injury (PETAL) (Other), Cardiothoracic Surgical Trials Network (CTSN) (Other), Medical Research Council (Other)

640

Enrollment

Locations

Arms

17.2

Anticipated Duration (Months)

21.3

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Covid19	Biological: Moderna mRNA-1273 COVID-19 vaccine Biological: Pfizer BNT162b2 COVID-19 vaccine	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

640 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 25, 2021

Anticipated Primary Completion Date :

Feb 1, 2023

Anticipated Study Completion Date :

Feb 1, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Neutralizing antibody (NAb) levels following vaccination [Thru Week 48]
Evaluated using the ratio of geometric mean responses

Secondary Outcome Measures

Antibody levels 12 weeks after first vaccination [12 weeks after first vaccination]
Evaluated using the ratio of geometric mean responses
Estimated percentage of participants with > 16-fold differences in NAbs [Baseline and Week 48]
Evaluated using the ratio of geometric mean responses
Estimated percentage of participants with > 16-fold differences in NAbs [Just before vaccination to 12 weeks post-vaccination]
Evaluated using the ratio of geometric mean responses
Estimated percentage of participants with 8-16-fold differences in NAbs [Baseline and Week 48]
Evaluated using the ratio of geometric mean responses
Estimated percentage of participants with 8-16-fold differences in NAbs [Just before vaccination to 12 weeks post-vaccination]
Evaluated using the ratio of geometric mean responses
Estimated percentage of participants with 4-8-fold differences in NAbs [Baseline and Week 48]
Evaluated using the ratio of geometric mean responses
Estimated percentage of participants with 4-8-fold differences in NAbs [Just before vaccination to 12 weeks post-vaccination]
Evaluated using the ratio of geometric mean responses
Estimated percentage of participants with 2-4-fold differences in NAbs [Baseline and Week 48]
Evaluated using the ratio of geometric mean responses
Estimated percentage of participants with 2-4-fold differences in NAbs [Just before vaccination to 12 weeks post-vaccination]
Evaluated using the ratio of geometric mean responses
Estimated percentage of participants with < 2-fold differences in NAbs [Baseline and Week 48]
Evaluated using the ratio of geometric mean responses
Estimated percentage of participants with < 2-fold differences in NAbs [Just before vaccination to 12 weeks post-vaccination]
Evaluated using the ratio of geometric mean responses
Ratio of post-vaccine level/pre-vaccine level [Up to Week 24]
Measured by change in NAb response
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars-Sinai Medical Center (Site 208-002), 8700 Beverly Blvd	Los Angeles	California	United States	90048
2	San Francisco VAMC (Site 074-002), 4150 Clement Street	San Francisco	California	United States	94121
3	Stanford University Hospitals & Clinics (Site 203-003), Stanford University, School of Medicine, 300 Pasteur Dr., Grant Bldg, Room S011	Stanford	California	United States	94305
4	Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center (Site 066-002), 1124 W. Carson St., CDCRC	Torrance	California	United States	90502
5	Public Health Institute at Denver Health (Site 017-004), 660 Bannock Street	Denver	Colorado	United States	80204
6	Washington DC VA Medical Center (Site 009-004), 50 Irving Street, NW.	Washington	District of Columbia	United States	20422
7	Hillsborough County Health Department, University of South Florida (Site 032-001), 1105 E. Kennedy Blvd.	Tampa	Florida	United States	33602
8	Minneapolis VA Medical Center (Site 105-001), 1 Veterans Drive	Minneapolis	Minnesota	United States	55417
9	Duke University Hospital (Site 301-006), 2301 Erwin Road	Durham	North Carolina	United States	27710
10	Wake Forest Baptist Health (Site 210-001), Medical Center Boulevard	Winston-Salem	North Carolina	United States	27157
11	Rhode Island Hospital (Site 080-036), 593 Eddy St.	Providence	Rhode Island	United States	02903
12	The Miriam Hospital (Site 080-039), 164 Summit Ave.	Providence	Rhode Island	United States	02906
13	CHRISTUS Spohn Shoreline Hospital (Site 080-001), 600 Elizabeth Street	Corpus Christi	Texas	United States	78404
14	UT Southwestern Medical Center (Site 084-001), 1936 Amelia Court, 2nd Floor	Dallas	Texas	United States	75235
15	Parkland Health and Hospital Systems (Site 084-002), James Aston Ambulatory Care Center - Clinical Research Unit, 5303 Harry Hines Blvd., Ste U-9.300	Dallas	Texas	United States	75390
16	Salem VA Medical Center (Site 074-014), 1970 Roanoke Blvd.	Salem	Virginia	United States	24153
17	Institute of Human Virology-Nigeria (Site 612-601), International Research Center of Excellence, Cadastral Zone COO Plot 62, after BAZE University, off CITEC Road	Abuja		Nigeria
18	Tan Tock Seng Hospital (Site 612-201), National Center for Infectious Diseases (NCID), 11 Jalan Tan Tock Seng	Singapore		Singapore	308433
19	Hospital Universitari Vall d'Hebron (Site 626-033), Passeig Vall Hebron, 119-129	Barcelona		Spain	08035
20	Hospital Clinic de Barcelona (Site 626-004), Carrer de Villaroel 170	Barcelona		Spain	08036
21	Hospital Universitari Germans Trias i Pujol (Site 626-003) Carretera de Canyet, s/n	Barcelona		Spain	08916
22	Hospital Universitari Arnau de Vilanova (Site 026-035), Institut de Recerca Biomèdica de Lleida, Av. Rovira Roure, 80	Lleida		Spain	25198
23	Hospital General Universitario Gregorio Marañón (Site 626-001), Servicio de Inmunología Clínica, Departamento de Medicina Interna, Dr. Esquerdo, 46	Madrid		Spain	28017
24	University Hospital Zurich (Site 621-201), Raemistrasse 100	Zürich		Switzerland	8091
25	MRC/UVRI & LSHTM Uganda Research Unit (Site 634-601), Plot 51-59 Nakiwogo Road, P.O. Box 49	Entebbe		Uganda	256
26	Gulu Regional Referral Hospital (Site 634-603), P.O. Box 160	Gulu		Uganda
27	St. Francis Hospital, Nsambya (Site 634-607), Nsambya Road Nsambya Hill, P.O. Box 7146	Kampala		Uganda	256
28	Makerere University Lung Institute (634-604), Mulago National Referral Hospital	Kampala		Uganda
29	Lira Regional Referral Hospital (Site 634-605), Plot 9/19, 21-41 Ngetta Road Police Road	Lira		Uganda
30	Masaka Regional Referral Hospital (Site 634-606), MRC/UVRI and LSHTM Uganda Research Unit, Plot 6 Circle Road, PO Box 556	Masaka		Uganda