Clinical trial NCT06742281: A Phase 2b, Randomized, Double-blind, Active-controlled Study of Single Dose CVXGA Intranasal COVID-19 Vaccine in Adults
Official title: A Phase 2b, Randomized, Double-blind, Active-controlled Study of Single Dose CVXGA (CVXGA50) Intranasal COVID-19 Vaccine in Adults
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: COVID-19
Keywords: COVID-19 intranasal vaccine
Lead sponsor: CyanVac LLC
Sponsor class: INDUSTRY
Collaborators: name: Biomedical Advanced Research and Development Authority
First posted: 2024-12-19
Enrollment: 10016
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to assess the safety and relative efficacy of CVXGA (CVXGA50), a KP.2 containing vaccine, compared to COMIRNATY® (COVID-19 Vaccine, mRNA; 2024-2025 Formula), a currently approved COVID-19 vaccine in the prevention of symptomatic, RT-PCR-confirmed SARS-CoV-2 infection. The trial will enroll up to 10016 healthy participants.

Detailed description: This is a double-blind, active comparator-controlled Phase 2b study to evaluate the efficacy, immunogenicity, and safety study in which eligible adult participants will be randomized 1:1 to receive CVXGA (CVXGA50) or COMIRNATY.

Number of Participants:

The proposed enrollment for this study is approximately 10,000 participants, plus an additional 16 participants enrolled in Sentinel Cohort 1 and Sentinel Cohort 2 (8 participants in each cohort).

Treatment Assignment:

Participants in Sentinel Cohort 1 and Sentinel Cohort 2 will be assigned to receive a single dose of CVXGA (CVXGA50) intranasally and will not receive an IM placebo.

All other participants in the study will be randomized 1:1 to receive a single dose of CVXGA (CVXGA50) intranasally (plus a single dose of IM placebo), or a single dose of IM COMIRNATY (plus a single dose of intranasal placebo).

Study visits: Participants will be asked to complete approximately 6-7 clinic visits, over a period of approximately 12 months duration per participant.

Eligibility criteria: Inclusion Criteria:

* Is an adult ≥18 years of age at time of screening.
* Has completed any WHO/FDA-authorized or approved primary COVID-19 vaccination series.
* Has received last COVID-19 vaccine no less than 6 months prior to study enrollment (study vaccination).
* If a female of childbearing potential who is sexually active, agrees to use an adequate method of birth control from Screening through 90 days after last study vaccination, and has used an adequate birth control method for at least 30 days prior to Screening.

A. Female of childbearing potential is defined as post onset menarche and pre-menopausal person capable of becoming pregnant. This does not include females who meet any of the following conditions: a) menopausal \>2 years; b) tubal ligation \>1 year; c) bilateral salpingo-oophorectomy; or d) hysterectomy.

B. Adequate contraception is defined as a contraceptive method with a failure rate of less than 1% per year when used consistently and correctly and when applicable, in accordance with the product label. Examples include: oral contraceptives, either combined or progestogen alone; injectable progestogen; implants of etonogestrel or levonorgestrel; estrogenic vaginal ring; percutaneous contraceptive patches; intrauterine device or intrauterine system; the female participant has exclusively female sexual partners; partner is sterile or otherwise unable to produce sperm (information on the person's sterility can come from the site personnel's review of the participant's medical records or interview with the participant regarding her medical history); male condom combined with a vaginal spermicide (foam, gel, film, cream, or suppository); or male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository).

* Is medically stable, as determined by the site investigator (based on review of health status, vital signs, medical history, and physical examination).
* Agrees to not participate in any other SARS-CoV-2 infection prevention trial (vaccine, drug, biologic, or pre-exposure prophylaxis \[PrEP\]) during participation in the study.
* Willing and able to provide informed consent prior to initiation of study procedures.
* Is available for all study visits, willing to participate in all study procedures, and not planning to relocate from the area for the duration of the study.

Exclusion Criteria:

* Has an acute illness, as determined by the site investigator, within 72 hours prior to Screening or study vaccination.

  (a. An acute illness that is nearly resolved, with only minor residual symptoms remaining, is allowable if, in the opinion of the site investigator, the residual symptoms will not interfere with the ability of study staff to assess safety parameters as required by the protocol.)
* Has had a positive COVID-19 test within the 90 days prior to Screening or study vaccination.
* Current or planned participation in any other interventional clinical trial.
* Prior receipt of a PIV5-based vaccine (e.g., CVXGA1, CVXGA35, or BLB201 \[an RSV vaccine being developed by CyanVac/Blue Lake Biotechnology\]).
* Participation in research involving any investigational product within 45 days prior to Screening or study vaccination.
* Receipt of any approved or authorized products intended to prevent SARS-CoV-2 infection within 6 months prior to Screening (complete list provided in the pharmacy manual).
* Receipt or anticipated receipt of, within 7 days prior through 31 days after study vaccination, any intranasal medication including FDA approved prescription or over-the-counter products or non-FDA approved alternative medicine products (e.g., intranasal Fluticasone {commonly used intranasal products that would be used, which is not herbal/naturopathic}, Ayurvedic oil or other naturopathic substances).
* Anticipated use of nasal irrigation (e.g., Neti PotTM) from Screening through 31 days after study vaccination.
* Receipt of blood products or immunoglobulins within 60 days prior to Screening or study vaccination.
* Received influenza vaccination within 14 days prior to Screening or study vaccination, or any other vaccine within 30 days prior to Screening or study vaccination.
* Any significant or uncontrolled autoimmune, immunodeficiency disease/condition, or autoinflammatory disorder (e.g. untreated or advanced human immunodeficiency virus \[HIV\] infection with CD4 counts \<200 cells/mm3, history of acquired immunodeficiency syndrome \[AIDS\] defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV).
* Unstable illness (acute or chronic illness) requiring significant medical monitoring and intervention during the 90 days prior to Screening or study vaccination.
* History of myocarditis, pericarditis, or idiopathic cardiomyopathy, or presence of any medical condition that, in the opinion of the investigator, increases risk of myocarditis or pericarditis.
* Administration of immunosuppressants, systemic glucocorticoids, or other immune-modifying drugs within the following timeframes:

  1. B-cell therapies within the 6 months prior to Screening or study vaccination.
  2. Prednisone, ≥20 mg for more than 2 weeks, within the 30 days prior to Screening or study vaccination.
  3. Monoclonal antibodies that may suppress aspects of immune response (e.g., Dupixent) within the 6 months prior to Screening or study vaccination.
  4. Other medications in this category, including but not limited to high-dose inhaled corticosteroids (\>800 mcg/day of beclomethasone dipropionate or equivalent); antimetabolites; transplant immunosuppressive agents; alkylating agents; cell-depleting agents; or cancer chemotherapeutics, within the 90 days prior to Screening or study vaccination.
  5. Any medication for any period of time that, in the opinion of the site investigator, could impede immune response to vaccination.
* Individuals who have close contact or high-risk contact with persons who may be severely immunocompromised, within 14 days following the study vaccination. High-risk contacts include but are not limited to:

  1. Residents of nursing homes or rehabilitation facilities
  2. Persons of any age with any significant immunodeficiency disease (e.g., untreated or advanced HIV, history of AIDS, or clinical manifestations of HIV)
  3. Persons of any age being administered immunosuppressants, systemic glucocorticoids, or other immune-modifying drugs
  4. Persons of any age with a known history of significant airway reactivity to viruses (e.g., severe asthma, advanced chronic obstructive disease, or cystic fibrosis)
  5. Persons of any age immunosuppressed due to cancer or undergoing active treatment for cancer
  6. Women who are pregnant, breastfeeding, or who plan to become pregnant during the study; and
  7. Infants age ≤6 months.
* Known contraindication to IM injection (e.g., bleeding diathesis, acquired coagulopathy) or to intranasal administration (e.g., severe nasal obstruction, significant chronic rhinitis, nasal septal defect causing significant breathing problems, unrepaired cleft palate, nasal polyps, or other nasal abnormality that, in the opinion of the investigator, may affect vaccine administration).
* History of significant/severe wheezing or respiratory symptoms resulting in hospitalization or known bronchial hyperreactivity to viruses.
* History of severe adverse reaction to vaccination in the past, including to COVID-19 vaccination.
* Any known allergies to components contained in CVXGA or COMIRNATY (including polyethylene glycol \[PEG\] allergies), or latex.
* Women who are pregnant, breastfeeding, or who plan to become pregnant during the study.
* Any other condition that, in the opinion of the site investigator, would pose a health risk to the participant if enrolled or could interfere with evaluation of the investigational product or interpretation of study results.
* Study team member or first-degree relative of any study team member (inclusive of CyanVac and site personnel involved in the study).

Primary outcomes:
measure: Percentage of participants with symptomatic COVID-19 after boost with CVXGA (CVXGA50) compared to COMIRNATY® (COVID-19 Vaccine, mRNA; 2024-2025 Formula) to compare differences in relative vaccine efficacy.
timeFrame: Day 14 to Day 366 post-vaccination.
Secondary outcomes:
measure: Time until first occurrence of molecularly confirmed (RT-PCR-positive) symptomatic COVID-19 for CVXGA (CVXGA50) compared to COMIRNATY to determine durability
timeFrame: Day 1 to Day 366 post-vaccination.
measure: Percentage of participants with asymptomatic COVID-19 after boost with CVXGA (CVXGA50) compared to COMIRNATY to determine relative efficacy.
timeFrame: Day 14 to Day 366 post-vaccination.
measure: Percentage of participants with severe COVID-19 after boost with CVXGA (CVXGA50) compared to COMIRNATY to determine relative efficacy.
timeFrame: Day 14 to Day 366 post-vaccination.
measure: The percentage of participants who experience any solicited local reactogenicity symptom pertaining to intranasal administration through 7 days post-vaccination.
timeFrame: Time Frame: Day 1 to Day 7 post-vaccination.
measure: The percentage of participants who experience any solicited local reactogenicity symptom pertaining to intramuscular (IM) administration through 7 days post-vaccination.
timeFrame: Day 1 to Day 7 post-vaccination.
measure: The percentage of participants who experience any solicited systemic reactogenicity symptom through 7 days post-vaccination.
timeFrame: Day 1 to Day 7 post-vaccination.
measure: The percentage of participants who experience any unsolicited adverse event (AE) through 30 days post-vaccination.
timeFrame: Day 1 to Day 30 post-vaccination.
measure: The percentage of participants who experience the following events through 12 months post-vaccination: o serious adverse events (SAEs) o medically attended adverse events (MAAEs) o adverse events of special interest (AESIs)
timeFrame: Day 1 to Day 366 post-vaccination.
measure: The percentage of participants with any new or worsening clinically significant abnormal safety laboratory result (serum chemistries and hematology) through 7 days post-vaccination.
timeFrame: Day 1 to Day 7 post-vaccination.
measure: Geometric mean titer (GMT) of SARS-CoV-2 specific neutralizing antibody (nAb) at Day 1 and Days 31, 91, 181, and 366 post-vaccination.
timeFrame: Day 1 to Day 366 post-vaccination.
measure: Geometric mean fold rise (GMFR) of SARS-CoV-2 specific nAb relative to Day 1 at Days 31, 91, 181, and 366 post-vaccination.
timeFrame: Day 1 to Day 366 post-vaccination.
measure: GMT of anti-spike (S) protein-specific binding antibody (bAb) at Day 1 and Days 31, 91, 181, and 366 post-vaccination.
timeFrame: Day 1 to Day 366 post-vaccination.
measure: GMFR of S protein-specific bAb relative to Day 1 at Days 31, 91, 181, and 366 post-vaccination.
timeFrame: Day 1 to Day 366 post-vaccination.
measure: GMT of S protein-specific IgA (nasal lining/saliva samples) at Day 1 and Days 31, 91, 181, and 366 post-vaccination.
timeFrame: Day 1 to Day 366 post-vaccination.
measure: GMFR of S protein-specific IgA (nasal lining/saliva samples) relative to Day 1 at Days 31, 91, 181, and 366 post-vaccination.
timeFrame: Day 1 to Day 366 post-vaccination.
measure: The percentage of subjects with increases in S-specific cytokine increases by cell type.
timeFrame: Day 1 to Day 366 post-vaccination.
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group, LLC
state: Alabama
city: Phoenix
country: United States
facility: Velocity Clinical Research, Phoenix
state: Arizona
city: Chula Vista
country: United States
facility: Velocity Clinical Research, Chula Vista
state: California
city: La Mesa
country: United States
facility: Velocity Clinical Research, San Diego
state: California
city: La Palma
country: United States
facility: Imax Clinical Trials
state: California
city: Riverside
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Riverside
country: United States
facility: Clinical Innovations Inc. dba CITrials
state: California
city: Sacramento
country: United States
facility: Avacare
state: California
city: Torrance
country: United States
facility: Collaborative Neuroscience Research, LLC
state: California
city: Washington
country: United States
facility: Velocity Clinical Research, Washington DC
state: District of Columbia
city: Hallandale Beach
country: United States
facility: Velocity Clinical Research, Hallandale Beach
state: Florida
city: Homestead
country: United States
facility: Homestead Associates in Research, Inc
state: Florida
city: North Miami Beach
country: United States
facility: Biscayne Clinical Research
state: Florida
city: Orlando
country: United States
facility: Headlands Research Orlando
state: Florida
city: Pembroke Pines
country: United States
facility: Best Choice Medical and Research Service
state: Florida
city: Tampa
country: United States
facility: Forcare Clinical Research
state: Florida
city: Tampa
country: United States
facility: Guardian Angel Research Center
state: Florida
city: Lilburn
country: United States
facility: Lifeline Primary Care/Avacare
state: Georgia
city: Savannah
country: United States
facility: Velocity Clinical Research, Savannah
state: Georgia
city: Stockbridge
country: United States
facility: Clinical Research Atlanta
state: Georgia
city: Meridian
country: United States
facility: Velocity Clinical Research, Boise
state: Idaho
city: Sioux City
country: United States
facility: Velocity Clinical Research, Sioux City
state: Iowa
city: Covington
country: United States
facility: Velocity Clinical Research, Covington
state: Louisiana
city: Lafayette
country: United States
facility: Velocity Clinical Research, Lafayette
state: Louisiana
city: New Orleans
country: United States
facility: Velocity Clinical Research, New Orleans
state: Louisiana
city: Gaithersburg
country: United States
facility: CBH Health
state: Maryland
city: Rockville
country: United States
facility: Advanced Primary and Geriatric Care/Avacare
state: Maryland
city: Rockville
country: United States
facility: Velocity Clinical Research, Rockville
state: Maryland
city: Southfield
country: United States
facility: DM Clinical Research
state: Michigan
city: Norfolk
country: United States
facility: Velocity Clinical Research - Norfolk
state: Nebraska
city: Omaha
country: United States
facility: Quality Clinical Research, Inc
state: Nebraska
city: Omaha
country: United States
facility: Velocity Clinical Research, Omaha
state: Nebraska
city: Jersey City
country: United States
facility: DM Clinical Research
state: New Jersey
city: Binghamton
country: United States
facility: Velocity Clinical Research, Binghamton
state: New York
city: Rochester
country: United States
facility: Rochester Clinical Research
state: New York
city: Wilmington
country: United States
facility: Trial Management Associates, LLC
state: North Carolina
city: Beachwood
country: United States
facility: Velocity Clinical Research, Cleveland
state: Ohio
city: Cincinnati
country: United States
facility: Velocity Clinical Research, Mt. Auburn
state: Ohio
city: Cincinnati
country: United States
facility: Velocity Clinical Research, Springdale
state: Ohio
city: Yukon
country: United States
facility: Tekton Research, LLC
state: Oklahoma
city: Philadelphia
country: United States
facility: DM Clinical Research
state: Pennsylvania
city: Anderson
country: United States
facility: Velocity Clinical Research, Anderson
state: South Carolina
city: Gaffney
country: United States
facility: Velocity Clinical Research Gaffney
state: South Carolina
city: Austin
country: United States
facility: Avacare
state: Texas
city: Austin
country: United States
facility: Tekton Research, LLC
state: Texas
city: Austin
country: United States
facility: Velocity Clinical Research, Austin
state: Texas
city: Brownsville
country: United States
facility: Pan American Clinical Research, LLC
state: Texas
city: Fort Worth
country: United States
facility: Avacare
state: Texas
city: Houston
country: United States
facility: DM Clinical Research
state: Texas
city: Houston
country: United States
facility: DM Clinical Research
state: Texas
city: San Angelo
country: United States
facility: Avacare
state: Texas
city: San Antonio
country: United States
facility: Tekton Research, LLC
state: Texas
city: West Jordan
country: United States
facility: Velocity Clinical Research, Salt Lake City
state: Utah
city: Richmond
country: United States
facility: Clinical Research Partners LLC
state: Virginia
city: Suffolk
country: United States
facility: Velocity Clinical Research, Suffolk
state: Virginia
Study officials:
affiliation: CyanVac LLC
name: Hong Jin
role: PRINCIPAL_INVESTIGATOR
References: