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Trial record 1 of 1 for:    COVAIL
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COVID-19 Variant Immunologic Landscape Trial (COVAIL Trial)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05289037
Recruitment Status : Active, not recruiting
First Posted : March 21, 2022
Last Update Posted : November 28, 2022
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

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.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: AS03 Biological: BNT162b2 Biological: BNT162b2 (B.1.1.529) Biological: BNT162b2 (B.1.351) Biological: BNT162b2 bivalent (wildtype and Omicron BA.1) Biological: BNT162b2 bivalent (wildtype and Omicron BA.4/BA.5) Biological: CoV2 preS dTM [B.1.351] Biological: CoV2 preS dTM/D614 Biological: CoV2 preS dTM/D614+B.1.351 Biological: mRNA-1273 Biological: mRNA-1273.351 Biological: mRNA-1273.529 Biological: mRNA-1273.617.2 Other: Sodium Chloride, 0.9% Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1270 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Phase 2 Clinical Trial to Optimize Immune Coverage of SARS-CoV-2 Existing and Emerging Variants
Actual Study Start Date : March 30, 2022
Estimated Primary Completion Date : March 28, 2026
Estimated Study Completion Date : March 28, 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm 01
mRNA-1273 administered through 0.2 mg/ml intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=100
Biological: mRNA-1273
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized spike (S) protein of the 2019 novel coronavirus (2019-nCoV).

Other: Sodium Chloride, 0.9%
0.9% Sodium Chloride Injection

Experimental: Arm 02
0.1 mg/ml of mRNA-1273.351 and 0.2 mg/ml of mRNA-1273.529 mg/ml administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=100
Biological: mRNA-1273.351
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the pre fusion stabilized spike (S) protein of the B.1.351 variant SARS-CoV-2 strain.

Biological: mRNA-1273.529
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.

Other: Sodium Chloride, 0.9%
0.9% Sodium Chloride Injection

Experimental: Arm 03
0.1 mg/ml of mRNA-1273.351 and 0.2 mg/ml of mRNA-1273.529 mg/ml administered through intramuscular injection in the deltoid muscle on Day 1 and Day 57 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=100
Biological: mRNA-1273.351
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the pre fusion stabilized spike (S) protein of the B.1.351 variant SARS-CoV-2 strain.

Biological: mRNA-1273.529
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.

Other: Sodium Chloride, 0.9%
0.9% Sodium Chloride Injection

Experimental: Arm 04
0.2 mg/ml of mRNA-1273.617.2 and 0.2 mg/ml of mRNA-1273.529 administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=100
Biological: mRNA-1273.529
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.

Biological: mRNA-1273.617.2
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized S protein of the B.1.617.2 (Delta) variant SARS-CoV-2 strain.

Other: Sodium Chloride, 0.9%
0.9% Sodium Chloride Injection

Experimental: Arm 05
0.2 mg/ml of mRNA-1273.529 administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=100
Biological: mRNA-1273.529
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.

Other: Sodium Chloride, 0.9%
0.9% Sodium Chloride Injection

Experimental: Arm 06
0.2 mg/ml of mRNA-1273.529 and mRNA-1273 0.2 mg/ml administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=100
Biological: mRNA-1273
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized spike (S) protein of the 2019 novel coronavirus (2019-nCoV).

Biological: mRNA-1273.529
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.

Other: Sodium Chloride, 0.9%
0.9% Sodium Chloride Injection

Experimental: Arm 07
500 mcg/mL of BNT162b2 (Wildtype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50
Biological: BNT162b2
A nucleoside-modified messenger RNA (modRNA) encoding the viral spike glycoprotein (S) of SARS-CoV-2.

Experimental: Arm 08
500 mcg/mL of BNT162b2 (Beta) and 500 mcg/mL of BNT162b2 (Omicron) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50
Biological: BNT162b2 (B.1.1.529)
A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer contains mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.

Biological: BNT162b2 (B.1.351)
A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer contains mRNA that encodes for the prefusion stabilized S protein of the B.1.351 (Beta) variant SARS-CoV-2 strain.

Experimental: Arm 09
500 mcg/mL of BNT162b2 (Omicron) administered through intramuscular injection in the deltoid muscle on Day 1 and Day 57 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50
Biological: BNT162b2 (B.1.1.529)
A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer contains mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.

Experimental: Arm 10
500 mcg/mL of BNT162b2 (Beta) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50
Biological: BNT162b2 (B.1.351)
A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer contains mRNA that encodes for the prefusion stabilized S protein of the B.1.351 (Beta) variant SARS-CoV-2 strain.

Experimental: Arm 11
500 mcg/mL of BNT162b2 (Beta) and 500 mcg/mL of BNT162b2 (Wildtype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50
Biological: BNT162b2
A nucleoside-modified messenger RNA (modRNA) encoding the viral spike glycoprotein (S) of SARS-CoV-2.

Biological: BNT162b2 (B.1.351)
A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer contains mRNA that encodes for the prefusion stabilized S protein of the B.1.351 (Beta) variant SARS-CoV-2 strain.

Experimental: Arm 12
500 mcg/mL of BNT162b2 (Omicron) and 500 mcg/mL of BNT162b2 (Wildtype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50
Biological: BNT162b2
A nucleoside-modified messenger RNA (modRNA) encoding the viral spike glycoprotein (S) of SARS-CoV-2.

Biological: BNT162b2 (B.1.1.529)
A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer contains mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.

Experimental: Arm 13
500 mcg/mL CoV2 preS dTM-AS03 [D614] (prototype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50
Drug: AS03
AS03 oil-in-water emulsion adjuvant.

Biological: CoV2 preS dTM/D614
Is a liquid formulation made of recombinant protein placed in a formulation buffer. The antigen solution contains the spike protein sequence of the ancestral strain of SARS-CoV-2.

Experimental: Arm 14
500 mcg/mL CoV2 preS dTM-AS03 [B.1.351] (Beta) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50
Drug: AS03
AS03 oil-in-water emulsion adjuvant.

Biological: CoV2 preS dTM [B.1.351]
Is a liquid formulation made of recombinant protein placed in a formulation buffer that contains the spike protein sequence of the B.1.351 (Beta) variant SARS-CoV-2 strain.

Experimental: Arm 15
500 mcg/mL CoV2 preS dTM-AS03 [D614 + B.1.351] (prototype + Beta) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50
Drug: AS03
AS03 oil-in-water emulsion adjuvant.

Biological: CoV2 preS dTM/D614+B.1.351
Is a liquid formulation made of recombinant protein placed in a formulation buffer contains the spike protein sequences of the ancestral and B.1.351 (Beta) variant SARS-CoV-2 strains

Experimental: Arm 16
100 mcg/mL BNT162b2 bivalent (wildtype and Omicron BA.1) + Wildtype (Prototype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 49 years; ( 45% in > / = 49 years) N=100
Biological: BNT162b2 bivalent (wildtype and Omicron BA.1)
A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer. Contains mRNA that encodes for the prefusion stabilized S protein of the Omicron BA.1 variant SARS-CoV-2 strain and the ancestral strain of SARS-CoV-2.

Experimental: Arm 17
100 mcg/mL BNT162b2 bivalent (wildtype and Omicron BA.4/BA.5) + Wildtype (Prototype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 49 years; ( 45% in > / = 49 years) N=100
Biological: BNT162b2 bivalent (wildtype and Omicron BA.4/BA.5)
A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer. Contains mRNA that encodes for the prefusion stabilized S protein of the Omicron BA.4/BA.5 variant SARS-CoV-2 strain and the ancestral strain of SARS-CoV-2.




Primary Outcome Measures :
  1. Change from baseline in Geometric Mean Fold Rise (GMFR) [ Time Frame: Day 1 through Day 366 ]
    As measured by Immunoglobin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA) or Multiplex Meso Scale Discovery (MSD) antibody binding assays to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) proteins. Neutralization titers will be calculated by neutralization assays using SARS-CoV-2 variant-specific S-pseudotyped viruses and different strains of live SARS-CoV-2.

  2. Change from baseline in Geometric Mean Titers (GMT) [ Time Frame: Day 1 through Day 366 ]
    As measured by Immunoglobin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA) or Multiplex Meso Scale Discovery (MSD) antibody binding assays to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) proteins. Neutralization titers will be calculated by neutralization assays using SARS-CoV-2 variant-specific S-pseudotyped viruses and different strains of live SARS-CoV-2.

  3. Change in Geometric Mean Ratio [ Time Frame: Day 1 through Day 366 ]
    As measured by Immunoglobin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA) or Multiplex Meso Scale Discovery (MSD) antibody binding assays to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) proteins. Neutralization titers will be calculated by neutralization assays using SARS-CoV-2 variant-specific S-pseudotyped viruses and different strains of live SARS-CoV-2.


Secondary Outcome Measures :
  1. Adverse Events (AEs) leading to withdrawal from the study [ Time Frame: Day 1 through Day 366 ]
  2. Incidence of Adverse Events of Special Interest (AESI) [ Time Frame: Day 1 through Day 366 ]
  3. Incidence of Medically Attended Adverse Events (MAAEs) [ Time Frame: Day 1 through Day 366 ]
  4. Incidence of New Onset Chronic Medical Conditions (NOCMCs) [ Time Frame: Day 1 through Day 366 ]
  5. Incidence of Serious Adverse Events (SAE) [ Time Frame: Day 1 through Day 366 ]
  6. Incidence of Solicited Adverse Events [ Time Frame: Day 1 through Day 8 ]
    Local and systemic events

  7. Incidence of Unsolicited Adverse Events [ Time Frame: Day 1 through Day 29 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05289037


Locations
Show Show 22 study locations
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
  Study Documents (Full-Text)

Documents provided by National Institute of Allergy and Infectious Diseases (NIAID):
Informed Consent Form  [PDF] May 31, 2022

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT05289037    
Other Study ID Numbers: 22-0004
5UM1AI148684-03 ( U.S. NIH Grant/Contract )
First Posted: March 21, 2022    Key Record Dates
Last Update Posted: November 28, 2022
Last Verified: October 3, 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Adaptive
COVAIL
Covid-19
Multivalent
Omicron
SARS-CoV-2
Vaccine
Variants
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases