Clinical trial NCT06680375: A Study of an Investigational Flu Seasonal/SARS-CoV-2 Combination Vaccine in Adults
Official title: A Phase 1/2, Randomized, Controlled Study to Evaluate the Reactogenicity, Safety, and Immunogenicity of an Investigational Flu Seasonal/SARS-CoV-2 Combination mRNA Vaccine in Adults
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: COVID-19
Keywords: Combination vaccine
Flu Seasonal
SARS-CoV-2 mRNA
Healthy younger adults
Healthy older adults
Safety
Reactogenicity
Immunogenicity
First time in humans
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2024-11-08
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study will evaluate the reactogenicity, safety, and immune response of Flu Seasonal/SARS-CoV-2 mRNA (mRNA Flu/COVID-19) combination vaccine. The flu portion will target multiple strains of the flu virus, while the COVID-19 part will focus on the spike protein of the SARS-CoV-2 virus. Both parts of this vaccine have been tested individually before. This will be the first study to test the combined vaccine in humans in healthy adult participants.

Detailed description: Click here to enter text.

Eligibility criteria: Inclusion Criteria:

* Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the eDiary, return for follow-up visits).
* Written informed consent obtained from the participant prior to performance of any study-specific procedure.
* A male or female 18-64 years of age (YA: 18-64) at the time of the study intervention administration.
* Participants must have a body mass index (BMI) \>=18 kg/m² and less than equal to (\<=) 40 kg/m2.
* Healthy participants or medically stable patients as established by medical history, clinical examination and (safety laboratory assessments). Participants with chronic medical conditions with or without specific treatment (e.g., chronic metabolic, cardiac, pulmonary, renal, hepatic, neurologic, and hematologic diseases) are allowed to participate in this study, if considered by the investigator as medically stable. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during 3 months before enrolment.
* Prior receipt of a COVID-19 vaccine. This may be from a completed primary vaccination series or booster dose(s) of an approved or authorized COVID-19 vaccine. The last COVID-19 vaccination must have been received at least 90 days prior to randomization.
* Women of non-childbearing potential may be enrolled in the study.
* Women of childbearing potential may be enrolled in the study if the participant:

  * has practiced adequate contraception for 4 weeks prior to study intervention administration, and
  * has a negative pregnancy test on the day of study intervention administration, and has agreed to continue adequate contraception for at least 8 weeks after completion of the study intervention administration.

Exclusion Criteria:

Medical conditions

* Any clinically significant hematological, biochemical laboratory abnormality.
* Participant tested positive for influenza by local health authority-approved testing methods within 180 days prior to Day 1.
* A documented history of confirmed SARS-CoV-2 infection within 90 days before study vaccination.
* Has had known close contact with anyone who had confirmed influenza or a confirmed SARS-CoV-2 infection within 2 weeks before study vaccination.
* Current or past malignancy, unless completely resolved without clinically significant sequelae (e.g., no evidence of disease following successful treatment of basal cell carcinoma cases are allowed) for \>5 years.
* Has any medical disease or psychiatric condition that, in the opinion of the investigator, precludes study participation because it would place the participant at an unacceptable risk of injury, would render them unable to meet the requirements of the protocol, or may interfere with successful completion of the study.
* Has a bleeding disorder (e.g., factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IM injections.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
* Any history of an immunosuppressive or immunodeficient condition resulting from disease (e.g., HIV infection or congenital immunodeficiency).
* Has a history of hypersensitivity or severe allergic reaction including anaphylaxis, generalized urticaria, angioedema, and other significant reactions to any previous mRNA or non-mRNA vaccine or any component of the study intervention(s) (including polyethylene glycol, egg proteins and aminoglycoside antibiotics)
* History of uncontrolled neurological disorders or seizures, including Guillain-Barré syndrome (within 6 weeks of receiving any vaccine) and Bell's Palsy, with the exception of febrile seizures during childhood.
* History of or current suspicion of myocarditis or pericarditis (including following administration of an mRNA vaccine); or idiopathic cardiomyopathy, or presence of any medical condition that increases the risk of myocarditis or pericarditis, including cocaine abuse, cardiomyopathy, endomyocardial fibrosis, hypereosinophilic syndrome, hypersensitivity myocarditis, eosinophilic granulomatosis with polyangiitis and persistent myocardial infection.
* Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study.

Prior/Concomitant therapy

* Use of any investigational or non-registered product (drug, vaccine or invasive medical device) other than the study intervention(s) during the period beginning 28 days before the dose of study intervention(s) (Day -28 to Day 1), or their planned use during the study period.
* Administration of any mRNA-based vaccine in the period starting 28 days (Day -28) before study intervention administration.
* Administration of any influenza vaccine within 180 days before enrolment or planned administration within 28 days (Day 29) after the study intervention administration.

Administration of a vaccine not foreseen by the study protocol in the period starting 28 days (Day -28) before the study intervention administration or planned administration within 28 days (Day 29) after the study intervention administration.

* Chronic administration of immune-modifying drugs (defined as more than 14 consecutive days in total) and/or planned use of long-acting immune-modifying treatments at any time up to the end of the study.

  * Up to 3 months prior to the study intervention administration and up to the end of study: For corticosteroids, this will mean prednisone equivalent \>=-20 mg/day. Inhaled, intra-articular and topical corticosteroids are allowed. If systemic corticosteroids have been administered short term (\<14 days) for treatment of an acute illness, participants should not be enrolled into the study until corticosteroid therapy has been discontinued for at least 28 days before study vaccine administration.
  * Up to 3 months prior to study intervention administration and up to the end of the study: long-acting immune-modifying drugs including among others immunotherapy (e.g., TNF-inhibitors), monoclonal antibodies, antitumoral medication.
* Administration of immunoglobulins and/or any blood products or plasma derivatives within 3 months before study vaccination through end of study.

Prior/Concurrent clinical study experience

• Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention.

Other exclusion criteria

* Participant is pregnant or has a positive pregnancy test result at Visit 1.
* Participant is breastfeeding or will (re)start breastfeeding between Day 1 (study vaccination) to 90 days after vaccination.
* Has a history of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential participant unable/unlikely to provide accurate safety reports or comply with study procedures.
* Participation of any study personnel or their immediate dependents, family, or household members.
* Participants with conditions precluding the assessment of local reactogenicity at the injection site (e.g, tattoos, scarring).
* Planned move during the study period that will prohibit participating in the study until study end.

Primary outcomes:
measure: Percentage of participants with increase in grading for at least one laboratory value from administration of study intervention
timeFrame: From Day 1 to Day 8
measure: Percentage of participants with solicited administration site adverse events (AEs)
timeFrame: From Day 1 to Day 7
measure: Percentage of participants with solicited systemic AEs
timeFrame: From Day 1 to Day 7
measure: Percentage of participants with unsolicited AEs
timeFrame: From Day 1 to Day 28
measure: Percentage of participants with medically attended adverse events (MAAEs)
timeFrame: From Day 1 to Day 183 (study end)
measure: Percentage of participants with serious adverse events (SAEs)
timeFrame: From Day 1 to Day 183 (study end)
measure: Percentage of participants with adverse events of special interest (AESIs)
timeFrame: From Day 1 to Day 183 (study end)
measure: Geometric mean titer (GMT) ratio of antigen 1 antibody for investigational mRNA Flu/COVID-19 (pooled dose 1 and dose 2) and mRNA flu vaccines
timeFrame: At Day 29
measure: GMT ratio of antigen 2 antibody for investigational mRNA Flu/COVID-19 (pooled dose 1 and dose 2) and mRNA flu seasonal vaccines
timeFrame: At Day 29
measure: GMT ratio of serum neutralization titers against pseudovirus bearing spike from SARS-CoV-2 vaccine matched variant(s) for investigational mRNA Flu/COVID-19 (pooled dose 1 and dose 2) and mRNA COVID-19 vaccines
timeFrame: At Day 29
Secondary outcomes:
measure: GMT ratio of antigen 1 antibody for the investigational mRNA Flu/COVID-19 vaccines (dose 1 and 2) and Flu vaccines (pooled group) and licensed Flu vaccine co-administered with a licensed mRNA COVID-19 vaccine
timeFrame: At Day 29
measure: GMT ratio of antigen 2 antibody for the investigational mRNA Flu/COVID-19 vaccines (dose 1 and 2) and Flu vaccines (pooled group) and licensed Flu vaccine co-administered with a licensed mRNA COVID-19 vaccine
timeFrame: At Day 29
measure: GMT ratio of serum neutralization titers against pseudovirus bearing spike from SARS-CoV-2 vaccine matched variant(s)
timeFrame: At Day 29
measure: GMTs of antigen 1 antibody for the investigational mRNA Flu/COVID-19 vaccines, mRNA Flu Seasonal vaccine and the licensed Flu Seasonal vaccine co-administered with a licensed mRNA COVID-19 vaccine
timeFrame: At Day 92 and Day 183 (Study end)
measure: Geometric mean increase (GMI) in antigen 1 antibody for the investigational mRNA Flu/COVID-19 vaccines, mRNA Flu Seasonal vaccine and the licensed Flu Seasonal vaccine co-administered with a licensed mRNA COVID-19 vaccine
timeFrame: From Day 1 to Day 29, from Day 1 to Day 92 and from Day 1 to Day 183 (study end)
measure: Seroconversion rate (SCR) of antigen 1 antibody for the investigational mRNA Flu/COVID-19 vaccines, mRNA Flu Seasonal vaccine and the licensed Flu Seasonal vaccine co-administered with a licensed mRNA COVID-19 vaccine
timeFrame: From Day 1 to Day 29, from Day 1 to Day 92 and from Day 1 to Day 183 (study end)
measure: Seroprotection rate (SPR) of antigen 1 antibody for the investigational mRNA Flu/COVID-19 vaccines, mRNA Flu Seasonal vaccine and the licensed Flu Seasonal vaccine co-administered with a licensed mRNA COVID-19 vaccine
timeFrame: At Day 1, Day 29, Day 92, and Day 183 (study end)
measure: GMTs of antigen 2 antibody for the investigational mRNA Flu/COVID-19 vaccines, mRNA Flu Seasonal vaccine and the licensed Flu Seasonal vaccine co-administered with a licensed mRNA COVID-19 vaccine
timeFrame: At Day 92 and Day 183 (study end)
measure: GMI in antigen 2 antibody for the investigational mRNA Flu/COVID-19 vaccines, mRNA Flu Seasonal vaccine and the licensed Flu Seasonal vaccine co-administered with a licensed mRNA COVID-19 vaccine
timeFrame: From Day 1 to Day 29, from Day 1 to Day 92 and from Day 1 to Day 183 (study end)
measure: SCR of antigen 2 antibody in for the investigational mRNA Flu/COVID-19 vaccines, mRNA Flu Seasonal vaccine and the licensed Flu Seasonal vaccine co-administered with a licensed mRNA COVID-19 vaccine
timeFrame: From Day 1 to Day 29, from Day 1 to Day 92 and from Day 1 to Day 183 (study end)
measure: GMTs of serum neutralization titers against pseudovirus bearing spike from SARS-CoV-2 vaccine matched variant(s)
timeFrame: At Day 92, and Day 183 (study end)
measure: GMI of neutralization titers against pseudovirus bearing spike from SARS-CoV-2 vaccine matched variant(s)
timeFrame: At Day 29, Day 92, and Day 183 (study end)
measure: Percentage of participants with seroresponse of neutralization titers against pseudovirus bearing spike from SARS-CoV-2 vaccine matched variant(s)
timeFrame: At Day 29, Day 92, and Day 183 (study end)
Other outcomes:
Locations:
city: Anniston
country: United States
facility: GSK Investigational Site
state: Alabama
city: Rolling Hills Estates
country: United States
facility: GSK Investigational Site
state: California
city: Hialeah
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Lenexa
country: United States
facility: GSK Investigational Site
state: Kansas
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Rochester
country: United States
facility: GSK Investigational Site
state: New York
Study officials:
References: