covid-19 variant immunologic landscape trial (covail trial)

Conditions: COVID-19

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.

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)

Keywords: adaptive covail covid-19 multivalent omicron sars-cov-2 vaccine variants