Clinical trial NCT05446740: A Study on the Safety, Reactogenicity and Immune Response of a Vaccine Against Influenza in Healthy Younger and Older Adults
Official title: A Phase 1 Randomized, Observer-blind, Dose-escalation Study to Evaluate the Safety, Reactogenicity and Immunogenicity of an mRNA-based Monovalent Influenza Vaccine Candidate in Healthy Younger and Older Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Influenza, Human
Keywords: Influenza
Safety
Reactogenicity
Immunogenicity
mRNA vaccine
Healthy younger adults
Healthy older adults
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: CureVac
First posted: 2022-07-07
Enrollment: 324
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: The purpose of this first-time-in-human (FTiH) study is to assess the safety, reactogenicity and immunogenicity of GlaxoSmithKline's (GSK) messenger RNA (mRNA)-based monovalent vaccine (GSK4382276A) candidate against influenza in healthy younger adults (YA) and older adults (OA).


Eligibility criteria: Inclusion Criteria:

* A male or female between and including 18 and 45 years of age (YAs) or between and including 60 and 80 years of age (OAs) at the time of the study intervention administration. The age of sentinel participants in OA category will be limited to maximum 70 years.
* Healthy or medically stable participants as established by medical history, safety laboratory assessments and clinical examination.
* Body mass index ≥ 18 kg/m\^2 and ≤ 32 kg/m\^2.
* Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
* Written informed consent obtained from the participant prior to performing any study-specific procedure.
* Female participants of non-childbearing potential may be enrolled in the study.
* Female participants of childbearing potential may be enrolled in the study if the participant:

  * has practiced adequate contraception for 28 days 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 1 month after study intervention administration.

Exclusion Criteria:

Medical conditions

* Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or review of the participant's medical record.
* Any clinically significant\* hematological coagulation or urine analysis laboratory abnormality.

  \* The investigator should use his/her clinical judgement to decide which abnormalities are clinically significant.
* Current or past malignancy, unless completely resolved without sequelae for \>5 years.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV infection, based on medical history and physical examination (no laboratory testing required).
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention (including latex, poly-ethylene-glycol, egg protein and aminoglycoside antibiotics).
* Recurrent history or uncontrolled neurological disorders or seizures, including Guillain-Barré syndrome and Bell's palsy, with the exception of febrile seizures during childhood.
* Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
* Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study.
* Significant exposure to persons with influenza or laboratory-confirmed SARS-CoV-2 within 7 days prior to Visit 1 (Day 1) and for whom a SARS-CoV-2 PCR test has not (yet) been confirmed as negative.

Prior/Concomitant therapy

* Administration of seasonal influenza vaccine within 180 days before enrollment or planned administration up to Visit 4 (Day 29).
* Administration of a vaccine not foreseen by the study protocol in the period starting 28 days before the study intervention administration, or planned administration within 28 days after the study intervention administration\*, with the exception of vaccines authorized or approved for the prevention of COVID-19 (regardless of the type of vaccine).

  \*In case emergency mass vaccination for an unforeseen public health threat is organized by public health authorities outside the routine immunization program, the time period described above can be reduced to 7 days, if necessary, for that mass vaccination vaccine, provided it is used according to the local governmental recommendations and that the Sponsor is notified accordingly.
* Use of any investigational or non-registered product (drug, vaccine or invasive medical device) other than the study intervention during the period beginning 30 days before the study intervention administration, or their planned use during the study period.
* Administration of long-acting immune-modifying drugs within 90 days before enrollment or planned use at any time during the study period.
* Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 90 days before the study intervention administration, or planned administration during the study period. Administration of monoclonal antibodies specifically directed against the spike protein of SARS-CoV-2 virus, for treatment of COVID-19 disease is allowed.
* Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the study intervention administration. For corticosteroids, this will mean prednisone equivalent ≥ 20 mg/day. Inhaled, topical and intraarticular steroids are allowed.
* Previous enrolment in this study.

Other exclusions

* Pregnant or lactating female.
* Female planning to become pregnant or planning to discontinue contraceptive precautions within the 1-month post-dosing period.
* History of abusive alcohol and/or drug consumption in the past 5 years.
* Any study personnel or their immediate dependents, family, or household members.
* Participants with extensive tattoos covering deltoid region on both arms that would preclude the assessment of local reactogenicity.

Primary outcomes:
measure: Number of participants reporting each solicited administration site event
timeFrame: From Day 1 to Day 7
measure: Number of participants reporting each solicited systemic event
timeFrame: From Day 1 to Day 7
measure: Number of participants reporting unsolicited adverse events (AEs)
timeFrame: From Day 1 to Day 28
measure: Number of participants reporting serious adverse events (SAEs)
timeFrame: From Day 1 to Day 183
measure: Number of participants reporting adverse events of special interest (AESIs)
timeFrame: From Day 1 to Day 183
measure: Number of participants reporting a shift from non-clinically significant laboratory value on Day 1 to clinically significant abnormal laboratory value on Day 8 or on Day 29 for hematology, clinical chemistry, coagulation and urine analysis
timeFrame: From Day 1 (pre-dose) to Day 8 (post-dose) or to Day 29 (post-dose)
measure: Geometric mean titers (GMT) of anti-vaccine antibody titers
timeFrame: At Day 1
measure: GMT of anti-vaccine antibody titers
timeFrame: At Day 22
measure: Geometric mean increase (GMI) of anti-vaccine antibody titers
timeFrame: From Day 1 to Day 22
measure: Anti-vaccine antibody titers seroconversion rate (SCR)
timeFrame: From Day 1 to Day 22
measure: Anti-vaccine antibody seroprotection rate (SPR)
timeFrame: At Day 22
Secondary outcomes:
measure: GMT of anti-vaccine antibody titer.
timeFrame: At Day 62 and Day 183
measure: GMI of anti-vaccine antibody titer
timeFrame: From Day 1 to Day 62
measure: GMI of anti-vaccine antibody titer
timeFrame: From Day 1 to Day 183
measure: Anti-vaccine antibody titer SPR
timeFrame: At Day 62 and Day 183
Other outcomes:
Locations:
city: Edegem
country: Belgium
facility: GSK Investigational Site
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Halifax
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: Sherbrooke
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: