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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- GlaxoSmithKline
- Enrollment
- 1,053
- Locations
- 1
- Primary Endpoint
- Number of Subjects With Any Solicited General Symptom After First Vaccination Dose
Study Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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.
Arms & Interventions
Group Low Dose_PLAIN_A
Subjects in Part A, aged 18-40 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted low dose on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.
Intervention: RSV Vaccine (GSK3844766A) unadjuvanted low dose (Biological)
Group Medium Dose_PLAIN_A
Subjects in Part A aged 18-40 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted medium dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.
Intervention: RSV Vaccine (GSK3844766A) unadjuvanted medium dose (Biological)
Group High Dose_PLAIN_A
Subjects in Part A aged 18-40 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted high dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.
Intervention: RSV Vaccine (GSK3844766A) unadjuvanted high dose (Biological)
Group Placebo_A
Subjects in Part A aged 18-40 years, receiving 2 doses of placebo (saline solution) control, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.
Intervention: Placebo (Saline solution) (Drug)
Group Low Dose_PLAIN_B
Subjects in Part B aged 60-80 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted low dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.
Intervention: RSV Vaccine (GSK3844766A) unadjuvanted low dose (Biological)
Group Low Dose_AS01E_B
Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01E, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.
Intervention: RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01E (Biological)
Group Low Dose_AS01B_B
Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01B, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.
Intervention: RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01B (Biological)
Group Medium Dose_PLAIN_B
Subjects in Part B aged 60-80 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted medium dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.
Intervention: RSV Vaccine (GSK3844766A) unadjuvanted medium dose (Biological)
Group Medium Dose_AS01E_B
Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) medium dose adjuvanted with AS01E, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.
Intervention: RSV Vaccine (GSK3844766A) medium dose adjuvanted with AS01E (Biological)
Group Medium Dose_AS01B_B
Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) medium dose adjuvanted with AS01B, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.
Intervention: RSV Vaccine (GSK3844766A) medium dose adjuvanted with AS01B (Biological)
Group High Dose_PLAIN_B
Subjects in Part B aged 60-80 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted high dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.
Intervention: RSV Vaccine (GSK3844766A) unadjuvanted high dose (Biological)
Group High Dose_AS01E_B
Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01E, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.
Intervention: RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01E (Biological)
Group High Dose_AS01B_B
Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01B, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.
Intervention: RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01B (Biological)
Group Placebo_B
Subjects in Part B aged 60-80 years, receiving 2 doses of placebo (saline solution) control, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.
Intervention: Placebo (Saline solution) (Drug)
Outcomes
Primary Outcomes
Number of Subjects With Any Solicited General Symptom After First Vaccination Dose
Time Frame: 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)
Assessed solicited general symptoms include arthralgia, fatigue, fever \[defined as temperature equal to or above 38.0 degrees Celsius (°C)\], gastrointestinal symptoms \[nausea, vomiting, diarrhea and/or abdominal pain\], headache, myalgia and shivering.
Number of Subjects With Any Unsolicited Adverse Events (AEs) After Any Vaccination Dose
Time Frame: During a 30-day follow-up period (i.e., on the day of vaccination and 29 subsequent days) after any vaccination dose (across doses)
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and/or any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any is defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Number of Subjects With Any Grade 3 Non-serious AEs (Solicited and Unsolicited) After Second Dose of Vaccination
Time Frame: 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
A Grade 3 AE is any AE assessed as severe, i.e. which prevents normal, everyday activities. In adults, such an AE would, for example, prevent attendance at work and would necessitate the administration of corrective therapy.
Number of Subjects With Any Serious Adverse Events (SAEs) up to 30 Days After the Second Vaccination
Time Frame: From first vaccination (Day 1) up to 30 days post second vaccination (Day 91)
A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity.
Number of Subjects With Any Solicited Local Symptoms After First Vaccination Dose
Time Frame: 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)
Assessed solicited local AEs at injection site are pain, erythema and swelling. Any erythema/swelling was scored as injection site erythema/swelling with a diameter larger than (\>) 20 millimeters (mm)
Number of Subjects With Any Solicited General Symptom After Second Vaccination Dose
Time Frame: 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)
Assessed solicited general symptoms include arthralgia, fatigue, fever \[defined as temperature equal to or above 38.0 degrees Celsius (°C)\], gastrointestinal symptoms \[nausea, vomiting, diarrhea and/or abdominal pain\], headache, myalgia and shivering.
Number of Subjects Presenting Change From Baseline in Hematology and Biochemistry With Respect of Normal Laboratory Ranges, After Second Vaccine Dose (Part A Groups)
Time Frame: At baseline and at 7 days after the second vaccine dose (Day 68)
Assessed hematological laboratory parameters include basophils, eosinophils, erythrocytes, hemoglobin, lymphocytes, monocytes, neutrophils, platelets, white blood cells. Biochemical laboratory parameters include alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], creatinine, urea nitrogen and uric acid. Categories reported when comparing Day 61 (pre-vaccination dose 2=baseline) and Day 68 hematological and biochemical laboratory results are defined as follows: \<parameter\>-\<range at baseline\>-\<range at timing\> (e.g. ALT-Within-Within). Ranges level being classified as unknown, below, within or above the normal ranges.
Number of Subjects With Any Solicited Local Symptoms After Second Vaccination Dose
Time Frame: 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)
Assessed solicited local AEs at injection site are pain, erythema and swelling. Any erythema/swelling was scored as injection site erythema/swelling with a diameter larger than (\>) 20 millimeters (mm)
Number of Subjects Presenting Change From Baseline in Hematology and Biochemistry With Respect of Normal Laboratory Ranges, After Second Vaccine Dose (Part B Groups)
Time Frame: At baseline and at 7 days after the second vaccine dose (Day 68)
Assessed hematological laboratory parameters include basophils, eosinophils, erythrocytes, hemoglobin, lymphocytes, monocytes, neutrophils, platelets, white blood cells. Biochemical laboratory parameters include alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], creatinine, urea nitrogen and uric acid. Categories reported when comparing Day 61 (pre-vaccination dose 2=baseline) and Day 68 hematological and biochemical laboratory results are defined as follows: \<parameter\>-\<range at baseline\>-\<range at timing\> (e.g. ALT-Within-Within). Ranges level being classified as unknown, below, within or above the normal ranges.
Number of Subjects With Any Grade 3 Non-serious AEs (Solicited and Unsolicited) After First Dose of Vaccination
Time Frame: 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
A Grade 3 AE is any AE assessed as severe, i.e. which prevents normal, everyday activities. In adults, such an AE would, for example, prevent attendance at work and would necessitate the administration of corrective therapy.
Number of Subjects Presenting Change From Baseline in Hematology and Biochemistry With Respect of Normal Laboratory Ranges, After First Vaccine Dose (Part A Groups)
Time Frame: At baseline and at 7 days after the first vaccine dose (Day 8)
Assessed hematological laboratory parameters include basophils, eosinophils, erythrocytes, hemoglobin, lymphocytes, monocytes, neutrophils, platelets, white blood cells. Biochemical laboratory parameters include alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], creatinine, urea nitrogen and uric acid. Categories reported when comparing Day 1 (pre-vaccination dose 1=baseline) and Day 8 hematological and biochemical laboratory results are defined as follows: \<parameter\>-\<range at baseline\>-\<range at timing\> (e.g. ALT-Within-Within). Ranges level being classified as unknown, below, within or above the normal ranges.
Number of Subjects Presenting Change From Baseline in Hematology and Biochemistry With Respect of Normal Laboratory Ranges, After First Vaccine Dose (Part B Groups)
Time Frame: At baseline and at 7 days after the first vaccine dose (Day 8)
Assessed hematological laboratory parameters include basophils, eosinophils, erythrocytes, hemoglobin, lymphocytes, monocytes, neutrophils, platelets, white blood cells. Biochemical laboratory parameters include alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], creatinine, urea nitrogen and uric acid. Categories reported when comparing Day 1 (pre-vaccination dose 1=baseline) and Day 8 hematological and biochemical laboratory results are defined as follows: \<parameter\>-\<range at baseline\>-\<range at timing\> (e.g. ALT-Within-Within). Ranges level being classified as unknown, below, within or above the normal ranges.
Number of Subjects With Any Potential Immune-mediated Diseases (pIMDs) up to 30 Days After the Second Vaccination (Part B Groups)
Time Frame: From first vaccination (Day 1) up to 30 days post second vaccination (Day 91)
pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.
Secondary Outcomes
- Number of Subjects With Any SAEs, up the End of Follow-up Period (Month 14) - Part B Groups(From Day 1 up to the end of follow-up period (Month 14))
- Number of Subjects With at Least One RSV-confirmed Respiratory Tract Infection (RTI) Episode Post-vaccination Reported During RTI Surveillance - Part B Groups(During the RSV season (from October 2019 to March 2020))
- Number of Subjects Reporting pIMDs up to the End of Follow-up Period (Month 14) - Part B Groups(From Day 1 up to the end of follow-up period (Month 14))
- Humoral Immune Response With Respect to Components of the Investigational Vaccine in Terms of Neutralizing Antibody Titers Against RSV-serotype A(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))
- Descriptive Statistics of the Frequency of RSVPreF3 Specific Cluster of Differentiation 4+ (CD4+) T Cells Expressing at Least 2 Markers(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))
- Humoral Immune Response With Respect to Components of the Investigational Vaccine in Terms of RSVPreF3-specific Immunoglobulin G (IgG) Antibody Concentrations(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))