Respiratory Syncytial Virus Infections
Conditions
Keywords
Respiratory syncytial virus, Adults aged 60 years and above, Lot-to-lot consistency, Safety, Reactogenicity
Brief summary
The purpose of this study is to assess the lot-to-lot consistency in terms of immunogenicity and evaluate the safety and reactogenicity of 3 lots of the RSVPreF3 OA investigational vaccine administered as a single dose in adults ≥ 60 years of age (YOA).
Interventions
BIOLOGICALRSVPreF3 OA investigational vaccine
One dose of a unique combination of the RSVPreF3 antigen lots (Lot 1, Lot 2 or Lot 3) and extemporaneously reconstituted with AS01E adjuvant lots (Lot A, Lot B and Lot C), administered intramuscularly in the deltoid region of the non-dominant arm, at Day 1.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Study is double blind from start to final analysis after which the study is considered single blind.
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol. A male or female ≥ 60 YOA at the time of first study intervention administration. * Participants living in the general community or in an assisted living facility that provides minimal assistance, such that the participant is primarily responsible for self care and activities of daily living. * Written or witnessed informed consent obtained from the participant prior to performance of any study specific procedure. * Participants who are medically stable in the opinion of the investigator at the time of vaccination. Participants with chronic stable medical conditions with or without specific treatment, such as diabetes, hypertension or cardiac disease, can participate in this study if considered by the investigator as medically stable.
Exclusion criteria
Medical conditions * Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease or immunosuppressive/cytotoxic therapy, 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(s). * Hypersensitivity to latex. * Serious or unstable chronic illness. * Any history of dementia or any medical condition that moderately or severely impairs cognition. * Recurrent or un controlled neurological disorders or seizures. Participants with medically controlled active or chronic neurological diseases can be enrolled in the study as per investigator assessment, provided that their condition will allow them to comply with the requirements of the protocol. * Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study. * Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe. Prior/Concomitant therapy * Use of any investigational or non registered product (drug, vaccine or medical device) other than the study intervention(s) during the period beginning 30 days before study intervention administration and ending 30 days after study intervention administration, or planned use during the study period. * Planned or actual administration of a vaccine not foreseen by the study protocol in the period starting 30 days before and ending 30 days after the study intervention administration, with the exception of inactivated and subunit influenza vaccines which can be administered up to 14 days before or from 14 days after the study vaccination. * Note: In case an emergency mass vaccination for an unforeseen public health threat (e.g. a pandemic) is recommended and/or organized by the public health authorities, outside the routine immunization program, the time period described above can be reduced if necessary for that vaccine provided it is used according to the local governmental recommendations and that the Sponsor is notified accordingly. Previous vaccination with an RSV vaccine. * Administration of long acting immune modifying drugs or planned administration 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 administration of the study intervention or planned administration during the study period. * Chronic administration (defined as more than 14 consecutive days in total) of immunosuppressants or other immune modifying drugs during the period starting 90 days prior to the study intervention administration or planned administration during the study period. For corticosteroids, this will mean prednisone ≥ 20 mg/day or equivalent. Inhaled and topical steroids are allowed. 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 vaccine/product (drug or invasive medical device). Other exclusions * 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. * Planned move during the study period that will prohibit participating in the study until study end. * Bedridden participants. * Participation of any study personnel or their immediate dependents, family, or household members.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| RSVPreF3 Specific Immunoglobin (Ig)G Antibody Concentrations Expressed as Group Geometric Mean Concentration (GMC) | At 30 days post-vaccination (Day 31) | Enzyme-linked immunosorbent assay (ELISA) was used to assess the concentrations of IgG antibodies against RSV PreF3 in serum samples. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Reporting Solicited Administration Site Events | Within 4 days (the day of vaccination and 3 subsequent days) after study intervention administration | Solicited administration site adverse events (AEs) assessed were erythema, pain and swelling. Any = occurrence of the adverse event regardless of intensity grade. |
| Percentage of Participants Reporting Solicited Systemic Events | Within 4 days (the day of vaccination and 3 subsequent days) after study intervention administration | Solicited systemic events assessed were arthralgia, fatigue, fever \[defined as temperature equal to or above (\>=) 38 degrees Celsius (°C)/100.4 degrees Fahrenheit (°F)}, headache and myalgia. Any = occurrence of the adverse event regardless of intensity grade or relation to study vaccination. |
| RSVPreF3 Specific IgG Antibody Concentrations Expressed as Mean Geometric Increase (MGI) | At 30 days post-vaccination (Day 31) | MGI was defined as the geometric mean of the within participant ratios of the post-vaccination RSV PreF3 IgG concentration over the pre-vaccination RSV PreF3 IgG concentration. |
| Percentage of Participants Reporting at Least One Serious Adverse Event (SAE) | From Day 1 up to study end (6 months after vaccination) | An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant. Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination. |
| Percentage of Participants Reporting at Least One Potential Immune-mediated Disease (pIMD) | From Day 1 up to study end (6 months after vaccination) | pIMDs are a subset of AEs of special interest that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. |
| Percentage of Participants Reporting at Least One Unsolicited Adverse Event | Within 30 days (the day of vaccination and 29 subsequent days) after study intervention administration | An unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited AE. Unsolicited AEs include serious, non-serious AEs and potential immune-mediated diseases (pIMDs). |
Countries
Canada, Sweden, United States
Participant flow
Pre-assignment details
Out of 770 participants enrolled 757 received the study vaccine and were included in the Exposed Set.
Participants by arm
| Arm | Count |
|---|---|
| RSV OA_Lot 1 Participants received 1 dose of a combination of the RSVPreF3 antigen Lot 1 and AS01E adjuvant Lot A at Day 1 and were followed up until the study end (Month 6). | 251 |
| RSV OA_Lot 2 Participants received 1 dose of a combination of the RSVPreF3 antigen Lot 2 and AS01E adjuvant Lot B at Day 1 and were followed up until the study end (Month 6). | 253 |
| RSV OA_Lot 3 Participants received 1 dose of a combination of the RSVPreF3 antigen Lot 3 and AS01E adjuvant Lot C at Day 1 and were followed up until the study end (Month 6). | 253 |
| Total | 757 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 2 |
| Overall Study | Lost to Follow-up | 2 | 3 | 3 |
Baseline characteristics
| Characteristic | RSV OA_Lot 1 | RSV OA_Lot 2 | RSV OA_Lot 3 | Total |
|---|---|---|---|---|
| Age, Continuous | 69.7 Years STANDARD_DEVIATION 6.6 | 70.1 Years STANDARD_DEVIATION 6.6 | 69.9 Years STANDARD_DEVIATION 6.6 | 69.9 Years STANDARD_DEVIATION 6.6 |
| Race/Ethnicity, Customized ASIAN | 6 Participants | 10 Participants | 10 Participants | 26 Participants |
| Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN | 6 Participants | 3 Participants | 4 Participants | 13 Participants |
| Race/Ethnicity, Customized NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized OTHER | 8 Participants | 8 Participants | 6 Participants | 22 Participants |
| Race/Ethnicity, Customized WHITE | 231 Participants | 231 Participants | 233 Participants | 695 Participants |
| Sex: Female, Male Female | 131 Participants | 131 Participants | 109 Participants | 371 Participants |
| Sex: Female, Male Male | 120 Participants | 122 Participants | 144 Participants | 386 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 251 | 2 / 253 | 2 / 253 |
| other Total, other adverse events | 181 / 251 | 192 / 253 | 195 / 253 |
| serious Total, serious adverse events | 8 / 251 | 6 / 253 | 7 / 253 |
Outcome results
Primary
RSVPreF3 Specific Immunoglobin (Ig)G Antibody Concentrations Expressed as Group Geometric Mean Concentration (GMC)
Enzyme-linked immunosorbent assay (ELISA) was used to assess the concentrations of IgG antibodies against RSV PreF3 in serum samples.
Time frame: At 30 days post-vaccination (Day 31)
Population: The analysis was performed on the Per Protocol set (PPS) which consisted of all eligible subjects who received the study intervention as per protocol, had immunogenicity results pre- and post dose, complied with blood draw intervals, without intercurrent conditions that may interfere with immunogenicity and without prohibited concomitant medication/vaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| RSV OA_Lot 1 | RSVPreF3 Specific Immunoglobin (Ig)G Antibody Concentrations Expressed as Group Geometric Mean Concentration (GMC) | 86039.9 ELISA Units/milliliter |
| RSV OA_Lot 2 | RSVPreF3 Specific Immunoglobin (Ig)G Antibody Concentrations Expressed as Group Geometric Mean Concentration (GMC) | 80518 ELISA Units/milliliter |
| RSV OA_Lot 3 | RSVPreF3 Specific Immunoglobin (Ig)G Antibody Concentrations Expressed as Group Geometric Mean Concentration (GMC) | 94260.9 ELISA Units/milliliter |
Comparison: To demonstrate the clinical equivalence of RSV OA\_Lot 1 versus RSV OA\_Lot 2 in terms of RSV PreF3 IgG concentrations expressed as group GMC ratio at one month post vaccination. The 2-sided 95% CI for group GMC ratio was derived from an ANCOVA model on log10 transformed RSV PreF3 IgG antibody titers. The ANCOVA model included the treatment group and the age category (age at vaccination: 60-69, 70-79 or \>=80 years) and the center as fixed effects and the pre-dose log10 titer as covariate.95% CI: [0.94, 1.21]
Comparison: To demonstrate the clinical equivalence of RSV OA\_Lot 1 versus RSV OA\_Lot 3 in terms of RSV PreF3 IgG concentrations expressed as group GMC ratio at one month post vaccination. The 2-sided 95% CI for group GMC ratio was derived from an ANCOVA model on log10 transformed RSV PreF3 IgG antibody titers. The ANCOVA model included the treatment group and the age category (age at vaccination: 60-69, 70-79 or \>=80 years) and the center as fixed effects and the pre-dose log10 titer as covariate.95% CI: [0.81, 1.04]
Comparison: To demonstrate the clinical equivalence of RSV OA\_Lot 2 versus RSV OA\_Lot 3 in terms of RSV PreF3 IgG concentrations expressed as group GMC ratio at one month post vaccination. The 2-sided 95% CI for group GMC ratio was derived from an ANCOVA model on log10 transformed RSV PreF3 IgG antibody titers. The ANCOVA model included the treatment group and the age category (age at vaccination: 60-69, 70-79 or \>=80 years) and the center as fixed effects and the pre-dose log10 titer as covariate.95% CI: [0.77, 0.99]
Secondary
Percentage of Participants Reporting at Least One Potential Immune-mediated Disease (pIMD)
pIMDs are a subset of AEs of special interest that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.
Time frame: From Day 1 up to study end (6 months after vaccination)
Population: The analysis was performed on the ES, which included all subjects who received the study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RSV OA_Lot 1 | Percentage of Participants Reporting at Least One Potential Immune-mediated Disease (pIMD) | 0.8 Percentage of participants |
| RSV OA_Lot 2 | Percentage of Participants Reporting at Least One Potential Immune-mediated Disease (pIMD) | 0.4 Percentage of participants |
| RSV OA_Lot 3 | Percentage of Participants Reporting at Least One Potential Immune-mediated Disease (pIMD) | 1.2 Percentage of participants |
Secondary
Percentage of Participants Reporting at Least One Serious Adverse Event (SAE)
An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant. Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination.
Time frame: From Day 1 up to study end (6 months after vaccination)
Population: The analysis was performed on the ES, which included all subjects who received the study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RSV OA_Lot 1 | Percentage of Participants Reporting at Least One Serious Adverse Event (SAE) | 3.2 Percentage of Participants |
| RSV OA_Lot 2 | Percentage of Participants Reporting at Least One Serious Adverse Event (SAE) | 2.4 Percentage of Participants |
| RSV OA_Lot 3 | Percentage of Participants Reporting at Least One Serious Adverse Event (SAE) | 2.8 Percentage of Participants |
Secondary
Percentage of Participants Reporting at Least One Unsolicited Adverse Event
An unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited AE. Unsolicited AEs include serious, non-serious AEs and potential immune-mediated diseases (pIMDs).
Time frame: Within 30 days (the day of vaccination and 29 subsequent days) after study intervention administration
Population: The analysis was performed on the ES, which included all subjects who received the study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RSV OA_Lot 1 | Percentage of Participants Reporting at Least One Unsolicited Adverse Event | 14.7 Percentage of participants |
| RSV OA_Lot 2 | Percentage of Participants Reporting at Least One Unsolicited Adverse Event | 14.6 Percentage of participants |
| RSV OA_Lot 3 | Percentage of Participants Reporting at Least One Unsolicited Adverse Event | 13.4 Percentage of participants |
Secondary
Percentage of Participants Reporting Solicited Administration Site Events
Solicited administration site adverse events (AEs) assessed were erythema, pain and swelling. Any = occurrence of the adverse event regardless of intensity grade.
Time frame: Within 4 days (the day of vaccination and 3 subsequent days) after study intervention administration
Population: The analysis was performed on participants of the Exposed Set (ES) who had their diary cards completed. The ES included all subjects who received the study intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RSV OA_Lot 1 | Percentage of Participants Reporting Solicited Administration Site Events | Pain | 58.2 Percentage of participants |
| RSV OA_Lot 1 | Percentage of Participants Reporting Solicited Administration Site Events | Erythema | 12.4 Percentage of participants |
| RSV OA_Lot 1 | Percentage of Participants Reporting Solicited Administration Site Events | Swelling | 6.8 Percentage of participants |
| RSV OA_Lot 2 | Percentage of Participants Reporting Solicited Administration Site Events | Pain | 65.7 Percentage of participants |
| RSV OA_Lot 2 | Percentage of Participants Reporting Solicited Administration Site Events | Erythema | 11.6 Percentage of participants |
| RSV OA_Lot 2 | Percentage of Participants Reporting Solicited Administration Site Events | Swelling | 7.6 Percentage of participants |
| RSV OA_Lot 3 | Percentage of Participants Reporting Solicited Administration Site Events | Erythema | 13.5 Percentage of participants |
| RSV OA_Lot 3 | Percentage of Participants Reporting Solicited Administration Site Events | Swelling | 7.9 Percentage of participants |
| RSV OA_Lot 3 | Percentage of Participants Reporting Solicited Administration Site Events | Pain | 62.7 Percentage of participants |
Secondary
Percentage of Participants Reporting Solicited Systemic Events
Solicited systemic events assessed were arthralgia, fatigue, fever \[defined as temperature equal to or above (\>=) 38 degrees Celsius (°C)/100.4 degrees Fahrenheit (°F)}, headache and myalgia. Any = occurrence of the adverse event regardless of intensity grade or relation to study vaccination.
Time frame: Within 4 days (the day of vaccination and 3 subsequent days) after study intervention administration
Population: The analysis was performed on participants of the Exposed Set (ES) who had their diary cards completed. The ES included all subjects who received the study intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RSV OA_Lot 1 | Percentage of Participants Reporting Solicited Systemic Events | Headache | 25.7 Percentage of participants |
| RSV OA_Lot 1 | Percentage of Participants Reporting Solicited Systemic Events | Fever | 2 Percentage of participants |
| RSV OA_Lot 1 | Percentage of Participants Reporting Solicited Systemic Events | Arthralgia | 13.3 Percentage of participants |
| RSV OA_Lot 1 | Percentage of Participants Reporting Solicited Systemic Events | Myalgia | 31.3 Percentage of participants |
| RSV OA_Lot 1 | Percentage of Participants Reporting Solicited Systemic Events | Fatigue | 28.1 Percentage of participants |
| RSV OA_Lot 2 | Percentage of Participants Reporting Solicited Systemic Events | Fatigue | 25.9 Percentage of participants |
| RSV OA_Lot 2 | Percentage of Participants Reporting Solicited Systemic Events | Arthralgia | 13.9 Percentage of participants |
| RSV OA_Lot 2 | Percentage of Participants Reporting Solicited Systemic Events | Fever | 1.6 Percentage of participants |
| RSV OA_Lot 2 | Percentage of Participants Reporting Solicited Systemic Events | Headache | 23.5 Percentage of participants |
| RSV OA_Lot 2 | Percentage of Participants Reporting Solicited Systemic Events | Myalgia | 34.3 Percentage of participants |
| RSV OA_Lot 3 | Percentage of Participants Reporting Solicited Systemic Events | Myalgia | 33.7 Percentage of participants |
| RSV OA_Lot 3 | Percentage of Participants Reporting Solicited Systemic Events | Headache | 22.2 Percentage of participants |
| RSV OA_Lot 3 | Percentage of Participants Reporting Solicited Systemic Events | Arthralgia | 14.7 Percentage of participants |
| RSV OA_Lot 3 | Percentage of Participants Reporting Solicited Systemic Events | Fever | 2.8 Percentage of participants |
| RSV OA_Lot 3 | Percentage of Participants Reporting Solicited Systemic Events | Fatigue | 27.8 Percentage of participants |
Secondary
RSVPreF3 Specific IgG Antibody Concentrations Expressed as Mean Geometric Increase (MGI)
MGI was defined as the geometric mean of the within participant ratios of the post-vaccination RSV PreF3 IgG concentration over the pre-vaccination RSV PreF3 IgG concentration.
Time frame: At 30 days post-vaccination (Day 31)
Population: The analysis was performed on the PPS which consisted of all eligible subjects who received the study intervention as per protocol, had immunogenicity results pre- and post dose, complied with blood draw intervals, without intercurrent conditions that may interfere with immunogenicity and without prohibited concomitant medication/vaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| RSV OA_Lot 1 | RSVPreF3 Specific IgG Antibody Concentrations Expressed as Mean Geometric Increase (MGI) | 11.84 Ratio |
| RSV OA_Lot 2 | RSVPreF3 Specific IgG Antibody Concentrations Expressed as Mean Geometric Increase (MGI) | 11.29 Ratio |
| RSV OA_Lot 3 | RSVPreF3 Specific IgG Antibody Concentrations Expressed as Mean Geometric Increase (MGI) | 12.46 Ratio |