Clinical trial NCT05289037: COVID-19 Variant Immunologic Landscape Trial (COVAIL Trial)
Official title: Phase 2 Clinical Trial to Optimize Immune Coverage of SARS-CoV-2 Existing and Emerging Variants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
Keywords: Adaptive
COVAIL
Covid-19
Multivalent
Omicron
SARS-CoV-2
Vaccine
Variants
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2022-03-21
Enrollment: 1270
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This phase 2 clinical trial will evaluate the safety and immunogenicity of additional doses of prototype and variant (alone or in combination) vaccine candidates in previously vaccinated participants with or without prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and will evaluate innate, cellular, and humoral immune responses to inform on how to shift the immune response to cover new variants as they emerge. A randomized open-label, non-placebo controlled, multi-site, multi-stage clinical trial in individuals, 18 years of age and older, who are in a stable state of health, has received a complete authorized/approved vaccine series (primary series + booster either with homologous or heterologous vaccine products) \>/ = 16 weeks prior to enrollment. Subjects will be stratified by i) age (18-64 years and = 65 years of age) (however arms 16 and 17 or stage 4 will only enroll participants between the ages of 18-49 years) and ii) history of confirmed prior SARS-CoV-2 infection, and randomly assigned to receive one of several variant vaccines. Enrollment will target a goal of approximately 45% of each of the variant vaccine arms to be in older adults (= 65 years of age) for stages 1, 2 and 3 and approximately 20% to have had confirmed COVID-19 for all 4 stages. The primary objective is to evaluate humoral immune responses of candidate SARS-CoV-2 variant vaccines, alone or in combination.

Detailed description: This phase 2 clinical trial will evaluate the safety and immunogenicity of additional doses of prototype and variant (alone or in combination) vaccine candidates in previously vaccinated participants with or without prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and will evaluate innate, cellular, and humoral immune responses to inform on how to shift the immune response to cover new variants as they emerge. A randomized open-label, non-placebo controlled, multi-site, multi-stage clinical trial in individuals, 18 years of age and older, who are in a stable state of health, has received a complete authorized/approved vaccine series (primary series + booster either with homologous or heterologous vaccine products) \>/= 16 weeks prior to enrollment. Subjects will be stratified by i) age (18-64 years and = 65 years of age) (however arms 16 and 17 or stage 4 will only enroll participants between the ages of 18-49 years) and ii) history of confirmed prior SARS-CoV-2 infection, and randomly assigned to receive one of several variant vaccines. Enrollment will target a goal of approximately 45% of each of the variant vaccine arms to be in older adults (= 65 years of age) for stages 1, 2 and 3 and approximately 20% to have had confirmed COVID-19 for all 4 stages. This is an adaptive design and may add arms of new vaccine platforms and/or variant lineage spike vaccines as needed. The study arms will be conducted in different stages (that could overlap) depending on public health needs and the availability of study products (starting with the available mRNA vaccines). The primary objective is to evaluate humoral immune responses of candidate SARS-CoV-2 variant vaccines, alone or in combination. The secondary objective is to evaluate the safety of candidate SARS-CoV-2 variant vaccines, as assessed by: a) Local and systemic solicited Adverse Events for 7 days following each vaccine dose; b) Unsolicited Adverse Events from Dose 1 to 28 days following each vaccine dose; c) Serious Adverse Events (SAEs), Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interests (AESIs), New Onset of Chronic Medical (NOCMCs) and Adverse Events (AEs) leading to withdrawal from the study from Dose 1 to 12 months after last vaccine dose.

Eligibility criteria: Inclusion Criteria:

Participants must meet all of the following criteria to be eligible to participate in this study:

1. Individuals \> / = 18 years of age at the time of consent. (18-49 years for stage 4).
2. Confirmed receipt of a complete primary and booster COVID-19 vaccine series, either homologous or heterologous, with an FDA authorized/approved vaccine at least 16 weeks prior to study vaccine dose 1.
3. Willing and able to comply with all scheduled visits, vaccination plan, laboratory tests and other study procedures.
4. Determined by medical history, targeted physical examination and clinical judgement of the investigator to be in stable state of health.

Note: Participants with pre-existing stable chronic medical conditions defined as condition not requiring significant change in therapy or hospitalization for worsening disease within 4 weeks from enrollment, can be included at the discretion of the investigator.

Exclusion Criteria:

Participants meeting any of the following criteria will be excluded from the study:

1. Confirmed SARS-CoV-2 infection \< 16 weeks prior to any study vaccine dose.
2. Pregnant and breastfeeding participants.
3. Prior administration of an investigational coronavirus vaccine at any time or SARS-CoV-2 immunoglobulin, monoclonal antibody or plasma antibody therapy in the preceding 3 months.

   Note: subjects that participated in clinical trials of products that are now FDA approved/authorized are allowed to participate.
4. Current/planned simultaneous participation in another interventional study or receipt of any investigational study product within 28 days prior to vaccine study dose(s).
5. A history of anaphylaxis, urticaria, or other significant adverse reaction requiring medical intervention after receipt of a vaccine, polyethylene glycol (PEG), polysorbate or nanolipid particles.
6. A history of myocarditis or pericarditis at any time prior to enrollment (for subjects in stages 1, 2 and 4).
7. Received or plans to receive a vaccine within 28 days prior to or after any dose of study vaccine.

   Note: Receipt of seasonal influenza vaccine is allowed at any time.
8. Bleeding disorder diagnosed by a healthcare provider (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or bleeding difficulties with intramuscular injections or blood draws.
9. Current or previous diagnosis of an immunocompromising condition or other immunosuppressive condition.
10. Advanced liver or kidney diseases.
11. Advanced (CD4 count \< 200) and/or untreated HIV, untreated Hepatitis B or untreated Hepatitis C.
12. Received oral, intramuscular or intravenous systemic immunosuppressants, or immune-modifying drugs for \>14 days in total within 6 months prior to any study vaccine dose (for corticosteroids = 20 mg \> / = day of prednisone equivalent).

    Note: Topical medications are allowed.
13. Received immunoglobulin or blood-derived products, within 3 months prior any study vaccine dose.
14. Received chemotherapy, immunotherapy or radiation therapy within 6 months prior to any study vaccine dose.
15. Study personnel or an immediate family member or household member of study personnel.
16. Is acutely ill or febrile 72 hours prior to or at vaccine dosing (fever defined as \> / = 38.0 degrees Celsius/100.4 degrees Fahrenheit). Participants meeting this criterion may be rescheduled within the relevant window periods.

    Note: Afebrile participants with minor illnesses can be enrolled at the discretion of the Investigator, as long as the illness is not suggestive of COVID-19.
17. Plan to receive a COVID-19 booster vaccine outside of the study within the next 180 days. (for subjects in Stage 4 only)

Primary outcomes:
measure: Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against Wa-1 in One Dose Groups.
timeFrame: Day 29, Day 91, Day 181, Day 271, Day 366
measure: Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against Wa-1 in Two Dose Group.
timeFrame: Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422
measure: Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against B.1.351 in One Dose Groups.
timeFrame: Day 29, Day 91, Day 181, Day 271, Day 366
measure: Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against B.1.351 in Two Dose Group.
timeFrame: Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422
measure: Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against BA.1 in One Dose Groups.
timeFrame: Day 29, Day 91, Day 181, Day 271, Day 366
measure: Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against BA.1 in Two Dose Group.
timeFrame: Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422
measure: Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against D614G in One Dose Groups.
timeFrame: Day 15, Day 29, Day 91, Day 181, Day 271, Day 366
measure: Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against D614G in Two Dose Group.
timeFrame: Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422
measure: Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against B.1.351 in One Dose Groups.
timeFrame: Day 15, Day 29, Day 91, Day 181, Day 271, Day 366
measure: Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against B.1.351 in Two Dose Group.
timeFrame: Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422
measure: Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against B.1.617.2 in One Dose Groups.
timeFrame: Day 15, Day 29, Day 91, Day 181, Day 271, Day 366
measure: Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against B.1.617.2 in Two Dose Group.
timeFrame: Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422
measure: Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against BA.1 in One Dose Groups.
timeFrame: Day 15, Day 29, Day 91, Day 181, Day 271, Day 366
measure: Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against BA.1 in Two Dose Group.
timeFrame: Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422
measure: Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against BA.2.12.1 in One Dose Groups.
timeFrame: Day 15
measure: Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against BA.4/BA.5 in One Dose Groups.
timeFrame: Day 15, Day 29, Day 91, Day 181, Day 271, Day 366
measure: Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against BA.4/BA.5 in Two Dose Group.
timeFrame: Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422
measure: Geometric Mean (GM) AUC of Antibody Against Wa-1 in One Dose Groups.
timeFrame: Day 1 Pre-Booster Dose, Day 29, Day 91, Day 181, Day 271, Day 366
measure: Geometric Mean (GM) AUC of Antibody Against Wa-1 in Two Dose Group.
timeFrame: Day 1 Pre-Booster Dose, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422
measure: Geometric Mean (GM) AUC of Antibody Against B.1.351 in One Dose Groups.
timeFrame: Day 1 Pre-Booster Dose, Day 29, Day 91, Day 181, Day 271, Day 366
measure: Geometric Mean (GM) AUC of Antibody Against B.1.351 in Two Dose Group.
timeFrame: Day 1 Pre-Booster Dose, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422
measure: Geometric Mean (GM) AUC of Antibody Against BA.1 in One Dose Groups.
timeFrame: Day 1 Pre-Booster Dose, Day 29, Day 91, Day 181, Day 271, Day 366
measure: Geometric Mean (GM) AUC of Antibody Against BA.1 in Two Dose Group.
timeFrame: Day 1 Pre-Booster Dose, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422
measure: Geometric Mean (GM) of Pseudovirus Neutralization Against D614G in One Dose Groups.
timeFrame: Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 271, Day 366
measure: Geometric Mean (GM) of Pseudovirus Neutralization Against D614G in Two Dose Group.
timeFrame: Day 1 Pre-Booster Dose, Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422
measure: Geometric Mean (GM) of Pseudovirus Neutralization Against B.1.351 in One Dose Groups.
timeFrame: Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 271, Day 366
measure: Geometric Mean (GM) of Pseudovirus Neutralization Against B.1.351 in Two Dose Group.
timeFrame: Day 1 Pre-Booster Dose, Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422
measure: Geometric Mean (GM) of Pseudovirus Neutralization Against B.1.617.2 in One Dose Groups.
timeFrame: Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 271, Day 366
measure: Geometric Mean (GM) of Pseudovirus Neutralization Against B.1.617.2 in Two Dose Group.
timeFrame: Day 1 Pre-Booster Dose, Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422
measure: Geometric Mean (GM) of Pseudovirus Neutralization Against BA.1 in One Dose Groups.
timeFrame: Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 271, Day 366
measure: Geometric Mean (GM) of Pseudovirus Neutralization Against BA.1 in Two Dose Group.
timeFrame: Day 1 Pre-Booster Dose, Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422
measure: Geometric Mean (GM) of Pseudovirus Neutralization Against BA.2.12.1 in One Dose Groups.
timeFrame: Day 1 Pre-Booster Dose, Day 15
measure: Geometric Mean (GM) of Pseudovirus Neutralization Against BA.4/BA.5 in One Dose Groups.
timeFrame: Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 271, Day 366
measure: Geometric Mean (GM) of Pseudovirus Neutralization Against BA.4/BA.5 in Two Dose Group.
timeFrame: Day 1 Pre-Booster Dose, Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422
measure: Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against B.1.351 in One Dose Groups.
timeFrame: Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 271, Day 366
measure: Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against B.1.351 in Two Dose Group.
timeFrame: Day 1 Pre-Booster Dose, Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422
measure: Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against B.1.617.2 in One Dose Groups.
timeFrame: Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 271, Day 366
measure: Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against B.1.617.2 in Two Dose Group.
timeFrame: Day 1 Pre-Booster Dose, Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422
measure: Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against BA.1 in One Dose Groups.
timeFrame: Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 271, Day 366
measure: Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against BA.1 in Two Dose Group.
timeFrame: Day 1 Pre-Booster Dose, Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422
measure: Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against BA.2.12.1 in One Dose Groups.
timeFrame: Day 1 Pre-Booster Dose, Day 15
measure: Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against BA.4/BA.5 in One Dose Groups.
timeFrame: Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 271, Day 366
measure: Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against BA.4/BA.5 in Two Dose Group.
timeFrame: Day 1 Pre-Booster Dose, Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422
Secondary outcomes:
measure: Frequency of Any Adverse Events (AEs) Leading to Withdrawal From the Study.
timeFrame: Day 1 to study completion (through up to Day 366) for Arms 1,2,4,5,6,7,8,9,10,11,12,13,14,15,16,17 and Day 1 to study completion (through up to Day 422) for Arm 3.
measure: Frequency of Any Adverse Events of Special Interest (AESIs)
timeFrame: Day 1 to study completion (through up to Day 366) for Arms 1,2,4,5,6,7,8,9,10,11,12,13,14,15,16,17 and Day 1 to study completion (through up to Day 422) for Arm 3.
measure: Frequency of Any Medically Attended Adverse Events (MAAEs)
timeFrame: Day 1 to study completion (through up to Day 366) for Arms 1,2,4,5,6,7,8,9,10,11,12,13,14,15,16,17 and Day 1 to study completion (through up to Day 422) for Arm 3.
measure: Frequency of Any New Onset Chronic Medical Conditions (NOCMCs)
timeFrame: Day 1 to study completion (through up to Day 366) for Arms 1,2,4,5,6,7,8,9,10,11,12,13,14,15,16,17 and Day 1 to study completion (through up to Day 422) for Arm 3.
measure: Frequency of Any Serious Adverse Events (SAEs)
timeFrame: Day 1 to study completion (through up to Day 366) for Arms 1,2,4,5,6,7,8,9,10,11,12,13,14,15,16,17 and Day 1 to study completion (through up to Day 422) for Arm 3.
measure: Frequency of Systemic Solicited Reactogenicity Adverse Events (AEs)
timeFrame: Day 1 through Day 8 for Arms 1, 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, and 17 and through 7 days post any vaccination for Arm 3.
measure: Frequency of Local Solicited Reactogenicity Adverse Events (AEs)
timeFrame: Day 1 through Day 8 for Arms 1, 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, and 17 and through 7 days post any vaccination for Arm 3.
measure: Frequency of Any Unsolicited Adverse Events (AEs)
timeFrame: Day 1 through Day 29 for Arms 1, 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, and 17 and 28 days post any vaccination for Arm 3.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham School of Medicine - Alabama Vaccine Research Clinic
state: Alabama
city: San Diego
country: United States
facility: University of California, San Diego (UCSD) - Antiviral Research Center (AVRC)
state: California
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General Hospital, UCSF Positive Health Program
state: California
city: Washington
country: United States
facility: George Washington University Medical Faculty Associates
state: District of Columbia
city: Washington
country: United States
facility: Howard University - Department of Medicine - Division of Infectious Disease
state: District of Columbia
city: Atlanta
country: United States
facility: Morehouse School of Medicine - Clinical Research Center
state: Georgia
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Decatur
country: United States
facility: The Hope Clinic of Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Illinois at Chicago College of Medicine - Division of Infectious Diseases
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics - Department of Internal Medicine
state: Iowa
city: New Orleans
country: United States
facility: Tulane University Clinical Translational Unit
state: Louisiana
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Saint Louis University Center for Vaccine Development
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis - Infectious Disease Clinical Research Unit
state: Missouri
city: Mineola
country: United States
facility: NYU Grossman School, NYU Langone Vaccine Center, Long Island
state: New York
city: New York
country: United States
facility: NYU Langone Vaccine Center Research Clinic, Manhattan
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center - Vaccine Research Unit
state: New York
city: Durham
country: United States
facility: Duke Vaccine and Trials Unit
state: North Carolina
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: League City
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Seattle
country: United States
facility: Kaiser Permanente Washington Health Research Institute
state: Washington
city: Seattle
country: United States
facility: The University of Washington - Virology Research Clinic
state: Washington
Study officials:
References:
citation: Branche AR, Rouphael NG, Diemert DJ, Falsey AR, Losada C, Baden LR, Frey SE, Whitaker JA, Little SJ, Anderson EJ, Walter EB, Novak RM, Rupp R, Jackson LA, Babu TM, Kottkamp AC, Luetkemeyer AF, Immergluck LC, Presti RM, Backer M, Winokur PL, Mahgoub SM, Goepfert PA, Fusco DN, Malkin E, Bethony JM, Walsh EE, Graciaa DS, Samaha H, Sherman AC, Walsh SR, Abate G, Oikonomopoulou Z, El Sahly HM, Martin TCS, Rostad CA, Smith MJ, Ladner BG, Porterfield L, Dunstan M, Wald A, Davis T, Atmar RL, Mulligan MJ, Lyke KE, Posavad CM, Meagher MA, Stephens DS, Neuzil KM, Abebe K, Hill H, Albert J, Lewis TC, Giebeig LA, Eaton A, Netzl A, Wilks SH, Tureli S, Makhene M, Crandon S, Lee M, Nayak SU, Montefiori DC, Makowski M, Smith DJ, Roberts PC, Beigel JH; COVAIL Study Group. SARS-CoV-2 Variant Vaccine Boosters Trial: Preliminary Analyses. medRxiv [Preprint]. 2022 Jul 15:2022.07.12.22277336. doi: 10.1101/2022.07.12.22277336.