Clinical trial NCT03814590: A Study to Assess the Safety, Reactogenicity and Immune Response of GlaxoSmithKline (GSK) Biologicals' Investigational Respiratory Syncytial Virus (RSV) Vaccine (GSK3844766A) in Older Adults
Official title: Phase I/II, Observer-blind, Safety, Reactogenicity and Immunogenicity Study of GSK Biologicals' Respiratory Syncytial Virus (RSV) Vaccine GSK3844766A in Subjects Aged 18-40 or 60-80 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Respiratory Syncytial Virus Infections
Keywords: Respiratory syncytial virus (RSV)
Vaccine
Safety
Reactogenicity
Immunogenicity
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2019-01-24
Enrollment: 1053
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the safety, reactogenicity and immune responses of two doses of the investigational RSV vaccines (with different formulations), when administered intramuscularly (IM) according to a 0, 2 month schedule, in older adults aged 60 to 80 years.

As the investigational vaccines have not yet been tested in humans before, the study will first assess the safety, reactogenicity and immune responses in young adults aged 18 to 40 years. The study will thus be conducted in 2 parts (Part A and Part B).


Eligibility criteria: Inclusion Criteria:

For all subjects:

* Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
* Written informed consent obtained from the subject prior to performing any study specific procedure.

For Part A:

• A male or female between, and including, 18 and 40 years of age at the time of the first vaccination.

For Part B:

* A male or female between, and including, 60 and 80 years of age at the time of the first vaccination.
* Subjects with residence status allowing free mixing with general community or in an assisted-living facility that provides minimal assistance, such that the subject is primarily responsible for self-care and activities of daily living.

Exclusion Criteria:

For all subjects:

* Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before the first dose of study vaccine, or planned use during the study period.
* Any medical condition that in the judgment of the investigator would make IM injection unsafe.
* Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting 6 months prior to the first vaccine dose. For corticosteroids, this will mean prednisone (≥ 20 mg/day, or equivalent). Inhaled and topical steroids are allowed.
* Administration of long-acting immune-modifying drugs or planned administration at any time during the study period.
* Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose and ending 30 days after the last dose of study vaccine administration, with the exception of inactivated and subunit influenza vaccines which can be administered up to 14 days before or from 30 days after each study vaccination.
* Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
* Hypersensitivity to latex.
* Serious or unstable chronic illness. Patients with chronic stable conditions with or without specific treatment, such as diabetes, hypertension or cardiac disease, are allowed to participate in this study.
* Any other condition (e.g. chronic obstructive pulmonary disease or severe respiratory condition) that, in the opinion of the investigator, might interfere with the evaluations required by the study.
* History of any neurological disorders or seizures.
* Acute disease and/or fever at the time of enrolment.
* Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by the investigator based on medical history, physical examination or laboratory screening tests.
* Hepatomegaly, right upper quadrant abdominal pain or tenderness.
* Administration of immunoglobulins and/or any blood products during the period starting 3 months before the first dose of study vaccine or planned administration during the study period.
* History of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports.
* Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study.
* Previous vaccination with an RSV vaccine.
* Lymphoproliferative disorder and malignancy within 5 years.
* Body mass index \> 40 kg/m².
* Planned move to a location that will prohibit participating in the trial until study end.
* At screening: Hematology parameters (complete blood cell count \[red blood cells, white blood cells\], white blood cells differential count \[lymphocytes, neutrophils and eosinophils\], platelets count or hemoglobin level) and/or biochemistry parameters (creatinine, blood urea nitrogen or liver enzymes \[alanine aminotransferase or aspartate aminotransferase\]) outside the normal laboratory ranges, unless the laboratory abnormalities are considered not clinically significant by the investigator.

For Part A:

* Pregnant or lactating female.
* Female subjects of childbearing potential, except if the subject:

  * has practiced adequate contraception for 30 days prior to vaccination, and
  * has a negative pregnancy test on the day of vaccination, and
  * has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.

For Part B:

* Known previous administration of a vaccine containing MPL, QS-21 and/or MF59 (e.g. GSK Biologicals' vaccine against human papillomavirus infection marketed as Cervarix, GSK Biologicals' Herpes Zoster vaccine marketed as Shingrix, an adjuvanted recombinant varicella zoster virus envelope gE subunit vaccine \[HZ/su\], or MF59 adjuvanted influenza vaccines \[e.g. Fluad\]).
* Planned administration of GSK Biologicals' Herpes Zoster vaccine marketed as Shingrix or an adjuvanted recombinant varicella zoster virus envelope gE subunit vaccine \[HZ/su\] within 180 days after the second dose of the study vaccine.
* Bedridden subjects.

Primary outcomes:
measure: Number of Subjects With Any Solicited Local Symptoms After First Vaccination Dose
timeFrame: During a 7-day follow-up period after first vaccination dose (i.e., on the day of vaccination [at Day 1] and 6 subsequent days)
measure: Number of Subjects With Any Solicited Local Symptoms After Second Vaccination Dose
timeFrame: During a 7-day follow-up period after second vaccination dose (i.e., on the day of vaccination [at Day 61] and 6 subsequent days)
measure: Number of Subjects With Any Solicited General Symptom After First Vaccination Dose
timeFrame: During a 7-day follow-up period after the first vaccination dose (i.e., on the day of vaccination [at Day 1] and 6 subsequent days)
measure: Number of Subjects With Any Solicited General Symptom After Second Vaccination Dose
timeFrame: During a 7-day follow-up period after the second vaccination dose (i.e., on the day of vaccination [at Day 61] and 6 subsequent days)
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs) After Any Vaccination Dose
timeFrame: During a 30-day follow-up period (i.e., on the day of vaccination and 29 subsequent days) after any vaccination dose (across doses)
measure: Number of Subjects Presenting Change From Baseline in Hematology and Biochemistry With Respect of Normal Laboratory Ranges, After First Vaccine Dose (Part A Groups)
timeFrame: At baseline and at 7 days after the first vaccine dose (Day 8)
measure: Number of Subjects Presenting Change From Baseline in Hematology and Biochemistry With Respect of Normal Laboratory Ranges, After First Vaccine Dose (Part B Groups)
timeFrame: At baseline and at 7 days after the first vaccine dose (Day 8)
measure: Number of Subjects Presenting Change From Baseline in Hematology and Biochemistry With Respect of Normal Laboratory Ranges, After Second Vaccine Dose (Part A Groups)
timeFrame: At baseline and at 7 days after the second vaccine dose (Day 68)
measure: Number of Subjects Presenting Change From Baseline in Hematology and Biochemistry With Respect of Normal Laboratory Ranges, After Second Vaccine Dose (Part B Groups)
timeFrame: At baseline and at 7 days after the second vaccine dose (Day 68)
measure: Number of Subjects With Any Grade 3 Non-serious AEs (Solicited and Unsolicited) After First Dose of Vaccination
timeFrame: During a 30-day follow-up period (i.e., on the day of vaccination at Day 1, and 29 subsequent days) after first dose of vaccination
measure: Number of Subjects With Any Grade 3 Non-serious AEs (Solicited and Unsolicited) After Second Dose of Vaccination
timeFrame: During a 30-day follow-up period (i.e., on the day of vaccination at Day 61, and 29 subsequent days) after second dose of vaccination
measure: Number of Subjects With Any Serious Adverse Events (SAEs) up to 30 Days After the Second Vaccination
timeFrame: From first vaccination (Day 1) up to 30 days post second vaccination (Day 91)
measure: Number of Subjects With Any Potential Immune-mediated Diseases (pIMDs) up to 30 Days After the Second Vaccination (Part B Groups)
timeFrame: From first vaccination (Day 1) up to 30 days post second vaccination (Day 91)
Secondary outcomes:
measure: Number of Subjects With Any SAEs, up the End of Follow-up Period (Month 14) - Part B Groups
timeFrame: From Day 1 up to the end of follow-up period (Month 14)
measure: Number of Subjects Reporting pIMDs up to the End of Follow-up Period (Month 14) - Part B Groups
timeFrame: From Day 1 up to the end of follow-up period (Month 14)
measure: Number of Subjects With at Least One RSV-confirmed Respiratory Tract Infection (RTI) Episode Post-vaccination Reported During RTI Surveillance - Part B Groups
timeFrame: During the RSV season (from October 2019 to March 2020)
measure: Humoral Immune Response With Respect to Components of the Investigational Vaccine in Terms of Neutralizing Antibody Titers Against RSV-serotype A
timeFrame: At pre-vaccination (Day 1), 30 days post-Dose 1 (Day 31), on the day of second vaccination (Day 61) and 30 days post-Dose 2 (Day 91)
measure: Humoral Immune Response With Respect to Components of the Investigational Vaccine in Terms of RSVPreF3-specific Immunoglobulin G (IgG) Antibody Concentrations
timeFrame: At pre-vaccination (Day 1), 30 days post-Dose 1 (Day 31), on the day of second vaccination (Day 61) and 30 days post-Dose 2 (Day 91)
measure: Descriptive Statistics of the Frequency of RSVPreF3 Specific Cluster of Differentiation 4+ (CD4+) T Cells Expressing at Least 2 Markers
timeFrame: At pre-vaccination (Day 1), 30 days post-Dose 1 (Day 31), on the day of second vaccination (Day 61) and 30 days post-Dose 2 (Day 91)
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Stockbridge
country: United States
facility: GSK Investigational Site
state: Georgia
city: Lenexa
country: United States
facility: GSK Investigational Site
state: Kansas
city: Wichita
country: United States
facility: GSK Investigational Site
state: Kansas
city: Elkridge
country: United States
facility: GSK Investigational Site
state: Maryland
city: Kansas City
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
city: Hickory
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Wilmington
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Medford
country: United States
facility: GSK Investigational Site
state: Oregon
city: Mount Pleasant
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: Wilrijk
country: Belgium
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Leroux-Roels I, Davis MG, Steenackers K, Essink B, Vandermeulen C, Fogarty C, Andrews CP, Kerwin E, David MP, Fissette L, Vanden Abeele C, Collete D, de Heusch M, Salaun B, De Schrevel N, Koch J, Verheust C, Dezutter N, Struyf F, Mesaros N, Tica J, Hulstrom V. Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F (RSVPreF3) Candidate Vaccine in Older Adults: Phase 1/2 Randomized Clinical Trial. J Infect Dis. 2023 Mar 28;227(6):761-772. doi: 10.1093/infdis/jiac327.