Respiratory Syncytial Virus
Conditions
Keywords
RSV, Older adults, MEDI7510, Vaccine, Efficacy
Brief summary
This study will be the first assessment of the efficacy of MEDI7510 for the prevention of respiratory syncytial virus (RSV) disease. It will also provide estimates of vaccine efficacy and of endpoint incidence in the placebo arm. It will also assess the safety and immunogenicity of concurrent dosing of MEDI7510 and IIV to expand on the observations made in the Phase 1b study of MEDI7510. It will also expand the safety database of participants dosed with MEDI7510. The study will also assess the immune response to MEDI7510 in Season 1 and Season 2.
Detailed description
A Phase 2b, double-blind, randomized, and controlled study to evaluate the efficacy of MEDI7510 in approximately 1,900 adult participants, globally, 60 years or older. Participants will be randomized in a 1:1 ratio to receive a single intramuscular dose of each of 2 study vaccines in contralateral arms: MEDI7510 + IIV or placebo + IIV in Season 1. Participants who receive MEDI7510 in the Northern Hemisphere will be re-randomized and blinded in Season 2 to receive either MEDI7510 + IIV or placebo + IIV in a 1:1 ratio. Clinical efficacy will not be assessed in Season 2; however the safety of revaccination will be assessed in Season 2.
Interventions
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to 99 Years
Healthy volunteers
Yes
Inclusion criteria
* Age ≥ 60 years at the time of screening. * Medically stable such that, according to the judgment of the investigator, hospitalization within the study period is not anticipated and the subject appears likely to be able to remain in follow-up through the end of protocol-specified follow-up. * (Season 2): Subject received MEDI7510 and IIV in the Northern Hemisphere in Season 1.
Exclusion criteria
* History of allergy to any component of the vaccine. * Receipt of seasonal influenza vaccine within 6 months prior to Season 1 dosing. * History of allergy to or intolerance of IIV. * Pregnancy or potential to become pregnant during the study. Females who (1) have had a menstrual period within the 12 months prior to study enrollment or (2) are undergoing any fertility treatment or who plan to undergo fertility treatments during the study period are excluded. * History of Guillain-Barré syndrome. * Previous vaccination against RSV. * History of allergy to eggs in adulthood. * History of or current autoimmune disorder, with the exception of stable, treated hypothyroidism caused by autoimmune thyroiditis, which is acceptable. * Immunosuppression caused by disease, including human immunodeficiency virus infection (assessed by history), or medications. Any receipt of oral or intravenous glucocorticoid therapy within 30 days prior to enrollment or planned dosing within the follow-up period would disqualify. Topical, intranasal, inhaled, or intra-articular corticosteroids do not disqualify. Expected need for immunosuppressive medications during the follow-up period would disqualify. * History of cancer within preceding 5 years other than treated non-melanoma skin cancer, locally-treated cervical cancer or in situ carcinoma of the breast. * Receipt of any non-study vaccine within 28 days prior to study dosing or expected receipt of non-study vaccine prior to the Day 29 visit in Season 1. * Receipt of any investigational product (IP) in the 90 days prior to randomization or expected receipt of IP during the period of study follow-up. * Receipt of immunoglobulins or blood products within 4 months of study dosing (120 days) or expected receipt of immunoglobulins or blood products during the period of study follow-up. * Current bleeding or clotting disorder including use of anticoagulants other than drugs with anti-platelet activity (such as nonsteroidal anti-inflammatory drugs, clopidogrel, ticagrelor or aspirin). * History of alcohol or drug abuse or psychiatric disorder that, in the opinion of the investigator, would affect the subject's safety or compliance with study. * (Season 2): Related Grade 3 or 4 adverse event (AE) including Grade 3 or 4 local reaction to either MEDI7510 or IIV, any adverse event of special interest (AESI) for an adjuvanted vaccine, or any related serious adverse event (SAE).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Had a First Episode of Acute Respiratory Syncytial Virus-Associated Respiratory Illness (ARA-RI) During Respiratory Syncytial Virus (RSV) Surveillance Period in Season 1 | Day 14 after dosing through end of surveillance period (approximately 7 months) | ARA-RI was defined as an event in which a participant met specified clinical criteria and the event was laboratory-confirmed to be RSV-related. The specified clinical criteria included a minimum of 1 symptom from any 2 of the 3 symptom columns: one symptom from upper respiratory symptom column and one symptom from lower respiratory symptom column; one symptom from upper respiratory symptom column and one symptom from systemic symptom column; or one symptom from lower respiratory column and one from systemic symptom column and laboratory confirmation of RSV on at least 1 sample obtained between Day 1 to Day 8 of illness. The surveillance period was approximately 7 months and Season 1 was approximately 1 year. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Responses (GMRs) of Serum Antibodies Concentration Against RSV by Anti-Fusion Protein (F) Immunoglobulin G (IgG) Assay | Day 1, Day 29, and End of Season 1 (approximately 1 year) | Anti-F IgG antibodies concentration were determined by a multiplex IgG assay developed on the Meso Scale discovery platform. It was calculated as: anti-log2 \[mean (log2 xi)\], where xi is an antibodies concentration of participants. The Season 1 was approximately 1 year. |
| Geometric Mean Fold Change of Serum Antibodies Concentration Against RSV by Anti-F IgG Assay | Day 29 and End of Season 1 (approximately 1 year) | Anti-F IgG antibodies concentration was determined by a multiplex IgG assay developed on the Meso Scale discovery platform. It was calculated as: anti-log2 \[mean (log2 yi)\], where yi is the post dose antibody concentration or T-cell count fold change from baseline for each participant. The Season 1 was approximately 1 year. |
| Percentage of Participants Who Had a Post-dose Seroresponse to RSV as Measured by Anti-F IgG Assay | Day 29 and End of Season 1 (approximately 1 year) | Anti-F IgG antibodies were determined by a multiplex IgG assay developed on the Meso Scale discovery platform. Seroresponse was defined as a greater than or equal to (\>=) 3-fold rise of serum antibodies against RSV from baseline. The Season 1 was approximately 1 year. |
| Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition (HAI) Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | Day 1 (post-dose) and Day 29 of Season 1 | GMT was calculated as: anti-log2 \[mean (log2 xi)\], where xi is an antibodies concentration of participants. GMTs of strain-Specific HAI antibodies (H1N1, H3N2, B Brisbane, and B Phuket) were reported. The Season 1 was approximately 1 year. |
| Post-dose Geometric Mean Fold Change of Strain-Specific HAI Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | Day 29 of Season 1 | Geometric mean fold change was calculated as: anti-log2 \[mean (log2 yi)\], where yi is the post dose antibody concentration or T-cell count fold change from baseline for each participant. Geometric mean fold change of strain-specific HAI antibodies (H1N1, H3N2, B BRISBANE, and B PHUKET) were reported. The Season 1 was approximately 1 year. |
| Percentage of Participants Who Had a Strain-specific Post-dose Seroresponse to HAI Antibody | Day 29 of Season 1 | Seroresponse was defined as a \>= 4-fold rise of strain-specific HAI antibodies (H1N1, H3N2, B BRISBANE, and B PHUKET) from baseline. The Season 1 was approximately 1 year. |
| Post-dose GMTs of Serum Antibodies Against RSV by Microneutralization Assay | Day 29 and End of Season 1 (approximately 1 year) | Microneutralization assay was to be used to assess humoral immunity (HAI antibody titers) against RSV. GMT was to be calculated as: anti-log2 \[mean (log2 xi)\], where xi is an antibodies concentration of participants. The Season 1 was approximately 1 year. |
| Percentage of Participants Who Had a RSV Polymerase Chain Reaction (PCR)-Positive Respiratory Illness During the RSV Surveillance Period in Season 1 | Day 14 after dosing through end of surveillance period (approximately 7 months) | Detection of RSV was done by PCR method by using any respiratory sample. The incidence of RSV PCR-positive respiratory illness during the RSV surveillance period was evaluated. The surveillance period was approximately 7 months and Season 1 was approximately 1 year. |
| Percentage of Participants Who Had a Post-dose Seroresponse to RSV by Microneutralization Assay | Day 29 and End of Season 1 (approximately 1 year) | Microneutralization assay was to be used to assess humoral immunity (HAI antibody titers) against RSV. Seroresponse was defined as a \>= 3-fold rise of Serum Antibodies against RSV from baseline. The Season 1 was approximately 1 year. |
| Post-dose Geometric Mean Concentration (GMC) of Palivizumab Competitive Antibodies as Measured by a Palivizumab Competitive Enzyme Linked Immunosorbent Assay (cELISA) | Day 29 and End of Season 1 (approximately 1 year) | Palivizumab cELISA assay was to be used to assess humoral immunity (HAI antibody titers) against RSV. GMC was to be calculated as: anti-log2 \[mean (log2 xi)\], where xi is an antibodies concentration of participants. The Season 1 was approximately 1 year. |
| Post-dose Geometric Mean Fold Change of Palivizumab Competitive Antibodies as Measured by a Palivizumab cELISA | Day 29 and End of Season 1 (approximately 1 year) | Palivizumab cELISA assay was to be used to assess humoral immunity (HAI antibody titers) against RSV. Geometric mean fold change was to be calculated as: anti-log2 \[mean (log2 yi)\], where yi is the post dose antibody concentration or T-cell count fold rise from baseline for each participant. The Season 1 was approximately 1 year. |
| Percentage of Participants Who Had a Post-dose Seroresponse to RSV as Measured by a Palivizumab cELISA | Day 29 and End of Season 1 (approximately 1 year) | Palivizumab cELISA assay was to be used to assess humoral immunity (HAI antibody titers) against RSV. Seroresponse was defined as a \>= 3-fold rise of Serum Antibodies against RSV from baseline. The Season 1 was approximately 1 year. |
| Number of Participants With Any Solicited Symptoms | Day 1 (post-dose) through Day 7 | Solicited symptoms: tenderness or soreness at site of injection, pain at site of injection, fatigue or tiredness, headache, generalized muscle aches, swelling at the site of injection, redness at the site of injection, fever \>= 100.4 degrees Fahrenheit by any route from Day 1 to Day 7. |
| Number of Participants With Treatment-Emergent Adverse Events | Day 1 (post-dose) through Day 29 | An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent events were between administration of study drug and Day 29 that were absent before treatment or that worsened relative to pre-treatment state. |
| Number of Participants With Treatment-Emergent Adverse Events of Special Interest (TEAESIs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment-Emergent New Onset Chronic Disease (NOCDs) | Day 1 (post-dose) through end of Season 1 (approximately 1 year) | An serious adverse event (SAE) was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between administration of study drug and approximately 1 year follow up that were absent before treatment or that worsened relative to pretreatment state. An adverse event of special interest was one of scientific and medical interest specific to understanding of study drug and may have required close monitoring and rapid communication by investigator to the sponsor. A NOCD was a newly diagnosed medical condition that is of a chronic, ongoing nature. It was observed after receiving study drug and was assessed by investigator as medically significant. The Season 1 was approximately 1 year. |
| Post-dose Geometric Mean Fold Change of Serum Antibodies Against RSV by Microneutralization Assay | Day 29 and End of Season 1 (approximately 1 year) | Microneutralization assay was to be used to assess humoral immunity (HAI antibody titers) against RSV. Geometric mean fold change was to be calculated as: anti-log2 \[mean (log2 yi)\], where yi is the post dose antibody concentration or T-cell count fold rise from baseline for each participant. The Season 1 was approximately 1 year. |
Countries
Canada, Chile, Estonia, Latvia, Lithuania, South Africa, United States
Participant flow
Recruitment details
A total of 1900 participants were randomized and participated in the study at 60 sites in 7 countries.
Pre-assignment details
A total of 2,044 participants were screened, of which 144 participants were screen failures and 1900 participants were randomized in the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo + IIV Participants received a single IM injection of placebo (matched with MEDI7510) in one arm and single IM injection of IIV in the contralateral arm. | 949 |
| MEDI7510 + IIV Participants received a single IM injection of MEDI7510 in one arm and single IM injection of IIV in the contralateral arm. | 951 |
| Total | 1,900 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 5 | 3 |
| Overall Study | Error in Randomization | 1 | 3 |
| Overall Study | Lost to Follow-up | 25 | 18 |
| Overall Study | Principal Investigator Decision | 1 | 2 |
| Overall Study | Withdrawal by Subject | 20 | 18 |
Baseline characteristics
| Characteristic | Placebo + IIV | MEDI7510 + IIV | Total |
|---|---|---|---|
| Age, Continuous | 68.1 Years STANDARD_DEVIATION 6.2 | 68.1 Years STANDARD_DEVIATION 6.3 | 68.1 Years STANDARD_DEVIATION 6.2 |
| Sex: Female, Male Female | 587 Participants | 530 Participants | 1117 Participants |
| Sex: Female, Male Male | 362 Participants | 421 Participants | 783 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 948 | 3 / 946 |
| other Total, other adverse events | 52 / 948 | 48 / 946 |
| serious Total, serious adverse events | 57 / 948 | 64 / 946 |
Outcome results
Primary
Percentage of Participants Who Had a First Episode of Acute Respiratory Syncytial Virus-Associated Respiratory Illness (ARA-RI) During Respiratory Syncytial Virus (RSV) Surveillance Period in Season 1
ARA-RI was defined as an event in which a participant met specified clinical criteria and the event was laboratory-confirmed to be RSV-related. The specified clinical criteria included a minimum of 1 symptom from any 2 of the 3 symptom columns: one symptom from upper respiratory symptom column and one symptom from lower respiratory symptom column; one symptom from upper respiratory symptom column and one symptom from systemic symptom column; or one symptom from lower respiratory column and one from systemic symptom column and laboratory confirmation of RSV on at least 1 sample obtained between Day 1 to Day 8 of illness. The surveillance period was approximately 7 months and Season 1 was approximately 1 year.
Time frame: Day 14 after dosing through end of surveillance period (approximately 7 months)
Population: Per-protocol population: All participants in the as-treated population (ATP) who were followed for qualifying symptoms for RSV until the end of the RSV surveillance period. Participants who met the primary endpoint criteria and were not followed until the end of the RSV surveillance period were also included in the per-protocol population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + IIV | Percentage of Participants Who Had a First Episode of Acute Respiratory Syncytial Virus-Associated Respiratory Illness (ARA-RI) During Respiratory Syncytial Virus (RSV) Surveillance Period in Season 1 | 1.6 Percentage of Participants |
| MEDI7510 + IIV | Percentage of Participants Who Had a First Episode of Acute Respiratory Syncytial Virus-Associated Respiratory Illness (ARA-RI) During Respiratory Syncytial Virus (RSV) Surveillance Period in Season 1 | 1.7 Percentage of Participants |
Comparison: 2 sided 90 percent (%) confidence interval (CI) was used to compare vaccine efficacy (VE). VE = (\[1 - relative risk (RR)\] \*100%), where RR was the RR of ARA-RI in the MEDI7510 group compared with the placebo group. A lower bound of the 90% CI greater than (\>) 0% would demonstrate the efficacy of MEDI7510.90% CI: [-106.9, 44.3]
Secondary
Geometric Mean Fold Change of Serum Antibodies Concentration Against RSV by Anti-F IgG Assay
Anti-F IgG antibodies concentration was determined by a multiplex IgG assay developed on the Meso Scale discovery platform. It was calculated as: anti-log2 \[mean (log2 yi)\], where yi is the post dose antibody concentration or T-cell count fold change from baseline for each participant. The Season 1 was approximately 1 year.
Time frame: Day 29 and End of Season 1 (approximately 1 year)
Population: Immunogenicity population for MEDI7510: All participants in the ATP who had no major protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response to MEDI7510.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Placebo + IIV | Geometric Mean Fold Change of Serum Antibodies Concentration Against RSV by Anti-F IgG Assay | Day 29 | 0.96 Fold Change |
| Placebo + IIV | Geometric Mean Fold Change of Serum Antibodies Concentration Against RSV by Anti-F IgG Assay | End of Season 1 | 0.94 Fold Change |
| MEDI7510 + IIV | Geometric Mean Fold Change of Serum Antibodies Concentration Against RSV by Anti-F IgG Assay | Day 29 | 12.78 Fold Change |
| MEDI7510 + IIV | Geometric Mean Fold Change of Serum Antibodies Concentration Against RSV by Anti-F IgG Assay | End of Season 1 | 4.60 Fold Change |
Secondary
Geometric Mean Responses (GMRs) of Serum Antibodies Concentration Against RSV by Anti-Fusion Protein (F) Immunoglobulin G (IgG) Assay
Anti-F IgG antibodies concentration were determined by a multiplex IgG assay developed on the Meso Scale discovery platform. It was calculated as: anti-log2 \[mean (log2 xi)\], where xi is an antibodies concentration of participants. The Season 1 was approximately 1 year.
Time frame: Day 1, Day 29, and End of Season 1 (approximately 1 year)
Population: Immunogenicity population for MEDI7510: All participants in the ATP who had no major protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response to MEDI7510.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Placebo + IIV | Geometric Mean Responses (GMRs) of Serum Antibodies Concentration Against RSV by Anti-Fusion Protein (F) Immunoglobulin G (IgG) Assay | Day 1 | 83.39 Fragment antigen-binding (F AB) unit/mL |
| Placebo + IIV | Geometric Mean Responses (GMRs) of Serum Antibodies Concentration Against RSV by Anti-Fusion Protein (F) Immunoglobulin G (IgG) Assay | Day 29 | 80.05 Fragment antigen-binding (F AB) unit/mL |
| Placebo + IIV | Geometric Mean Responses (GMRs) of Serum Antibodies Concentration Against RSV by Anti-Fusion Protein (F) Immunoglobulin G (IgG) Assay | End of Season 1 | 79.95 Fragment antigen-binding (F AB) unit/mL |
| MEDI7510 + IIV | Geometric Mean Responses (GMRs) of Serum Antibodies Concentration Against RSV by Anti-Fusion Protein (F) Immunoglobulin G (IgG) Assay | Day 1 | 77.96 Fragment antigen-binding (F AB) unit/mL |
| MEDI7510 + IIV | Geometric Mean Responses (GMRs) of Serum Antibodies Concentration Against RSV by Anti-Fusion Protein (F) Immunoglobulin G (IgG) Assay | Day 29 | 999.03 Fragment antigen-binding (F AB) unit/mL |
| MEDI7510 + IIV | Geometric Mean Responses (GMRs) of Serum Antibodies Concentration Against RSV by Anti-Fusion Protein (F) Immunoglobulin G (IgG) Assay | End of Season 1 | 370.88 Fragment antigen-binding (F AB) unit/mL |
Secondary
Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition (HAI) Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine
GMT was calculated as: anti-log2 \[mean (log2 xi)\], where xi is an antibodies concentration of participants. GMTs of strain-Specific HAI antibodies (H1N1, H3N2, B Brisbane, and B Phuket) were reported. The Season 1 was approximately 1 year.
Time frame: Day 1 (post-dose) and Day 29 of Season 1
Population: Immunogenicity population for IIV: All participants in the ATP who had no major protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response to the influenza vaccine.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Placebo + IIV | Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition (HAI) Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | H1N1, Day 1 | 54.26 Titer |
| Placebo + IIV | Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition (HAI) Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | H1N1, Day 29 | 161.26 Titer |
| Placebo + IIV | Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition (HAI) Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | H3N2, Day 1 | 34.81 Titer |
| Placebo + IIV | Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition (HAI) Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | H3N2, Day 29 | 291.73 Titer |
| Placebo + IIV | Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition (HAI) Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | B BRISBANE, Day 1 | 12.89 Titer |
| Placebo + IIV | Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition (HAI) Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | B BRISBANE, Day 29 | 32.49 Titer |
| Placebo + IIV | Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition (HAI) Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | B PHUKET, Day 1 | 11.42 Titer |
| Placebo + IIV | Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition (HAI) Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | B PHUKET, Day 29 | 30.00 Titer |
| MEDI7510 + IIV | Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition (HAI) Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | B PHUKET, Day 29 | 28.29 Titer |
| MEDI7510 + IIV | Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition (HAI) Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | H1N1, Day 1 | 55.77 Titer |
| MEDI7510 + IIV | Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition (HAI) Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | B BRISBANE, Day 1 | 13.46 Titer |
| MEDI7510 + IIV | Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition (HAI) Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | H1N1, Day 29 | 155.14 Titer |
| MEDI7510 + IIV | Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition (HAI) Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | B PHUKET, Day 1 | 11.81 Titer |
| MEDI7510 + IIV | Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition (HAI) Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | H3N2, Day 1 | 35.99 Titer |
| MEDI7510 + IIV | Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition (HAI) Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | B BRISBANE, Day 29 | 30.15 Titer |
| MEDI7510 + IIV | Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition (HAI) Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | H3N2, Day 29 | 269.58 Titer |
Secondary
Number of Participants With Any Solicited Symptoms
Solicited symptoms: tenderness or soreness at site of injection, pain at site of injection, fatigue or tiredness, headache, generalized muscle aches, swelling at the site of injection, redness at the site of injection, fever \>= 100.4 degrees Fahrenheit by any route from Day 1 to Day 7.
Time frame: Day 1 (post-dose) through Day 7
Population: ATP: Participants who received any dose of investigational product (IP). Participants were included in the ATP according to the IP received even if different from that to which the participant was randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo + IIV | Number of Participants With Any Solicited Symptoms | 558 Participants |
| MEDI7510 + IIV | Number of Participants With Any Solicited Symptoms | 606 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events
An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent events were between administration of study drug and Day 29 that were absent before treatment or that worsened relative to pre-treatment state.
Time frame: Day 1 (post-dose) through Day 29
Population: ATP: Participants who received any dose of IP. Participants were included in the ATP according to the IP received even if different from that to which the participant was randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo + IIV | Number of Participants With Treatment-Emergent Adverse Events | 141 Participants |
| MEDI7510 + IIV | Number of Participants With Treatment-Emergent Adverse Events | 146 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events of Special Interest (TEAESIs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment-Emergent New Onset Chronic Disease (NOCDs)
An serious adverse event (SAE) was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between administration of study drug and approximately 1 year follow up that were absent before treatment or that worsened relative to pretreatment state. An adverse event of special interest was one of scientific and medical interest specific to understanding of study drug and may have required close monitoring and rapid communication by investigator to the sponsor. A NOCD was a newly diagnosed medical condition that is of a chronic, ongoing nature. It was observed after receiving study drug and was assessed by investigator as medically significant. The Season 1 was approximately 1 year.
Time frame: Day 1 (post-dose) through end of Season 1 (approximately 1 year)
Population: ATP: Participants who received any dose of IP. Participants were included in the ATP according to the IP received even if different from that to which the participant was randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo + IIV | Number of Participants With Treatment-Emergent Adverse Events of Special Interest (TEAESIs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment-Emergent New Onset Chronic Disease (NOCDs) | TEAESIs | 0 Participants |
| Placebo + IIV | Number of Participants With Treatment-Emergent Adverse Events of Special Interest (TEAESIs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment-Emergent New Onset Chronic Disease (NOCDs) | TESAEs | 3 Participants |
| Placebo + IIV | Number of Participants With Treatment-Emergent Adverse Events of Special Interest (TEAESIs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment-Emergent New Onset Chronic Disease (NOCDs) | NOCDs | 5 Participants |
| MEDI7510 + IIV | Number of Participants With Treatment-Emergent Adverse Events of Special Interest (TEAESIs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment-Emergent New Onset Chronic Disease (NOCDs) | TEAESIs | 1 Participants |
| MEDI7510 + IIV | Number of Participants With Treatment-Emergent Adverse Events of Special Interest (TEAESIs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment-Emergent New Onset Chronic Disease (NOCDs) | TESAEs | 4 Participants |
| MEDI7510 + IIV | Number of Participants With Treatment-Emergent Adverse Events of Special Interest (TEAESIs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment-Emergent New Onset Chronic Disease (NOCDs) | NOCDs | 4 Participants |
Secondary
Percentage of Participants Who Had a Post-dose Seroresponse to RSV as Measured by Anti-F IgG Assay
Anti-F IgG antibodies were determined by a multiplex IgG assay developed on the Meso Scale discovery platform. Seroresponse was defined as a greater than or equal to (\>=) 3-fold rise of serum antibodies against RSV from baseline. The Season 1 was approximately 1 year.
Time frame: Day 29 and End of Season 1 (approximately 1 year)
Population: Immunogenicity population for MEDI7510: All participants in the ATP who had no major protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response to MEDI7510.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + IIV | Percentage of Participants Who Had a Post-dose Seroresponse to RSV as Measured by Anti-F IgG Assay | Day 29 | 0.8 Percentage of Participants |
| Placebo + IIV | Percentage of Participants Who Had a Post-dose Seroresponse to RSV as Measured by Anti-F IgG Assay | End of Season 1 | 1.6 Percentage of Participants |
| MEDI7510 + IIV | Percentage of Participants Who Had a Post-dose Seroresponse to RSV as Measured by Anti-F IgG Assay | Day 29 | 92.9 Percentage of Participants |
| MEDI7510 + IIV | Percentage of Participants Who Had a Post-dose Seroresponse to RSV as Measured by Anti-F IgG Assay | End of Season 1 | 65.8 Percentage of Participants |
Secondary
Percentage of Participants Who Had a Post-dose Seroresponse to RSV as Measured by a Palivizumab cELISA
Palivizumab cELISA assay was to be used to assess humoral immunity (HAI antibody titers) against RSV. Seroresponse was defined as a \>= 3-fold rise of Serum Antibodies against RSV from baseline. The Season 1 was approximately 1 year.
Time frame: Day 29 and End of Season 1 (approximately 1 year)
Population: Data for this outcome measure were not collected as the study was terminated prematurely because the study did not meet its primary efficacy outcome measure.
Secondary
Percentage of Participants Who Had a Post-dose Seroresponse to RSV by Microneutralization Assay
Microneutralization assay was to be used to assess humoral immunity (HAI antibody titers) against RSV. Seroresponse was defined as a \>= 3-fold rise of Serum Antibodies against RSV from baseline. The Season 1 was approximately 1 year.
Time frame: Day 29 and End of Season 1 (approximately 1 year)
Population: Data for this outcome measure were not collected as the study was terminated prematurely because the study did not meet its primary efficacy outcome measure.
Secondary
Percentage of Participants Who Had a RSV Polymerase Chain Reaction (PCR)-Positive Respiratory Illness During the RSV Surveillance Period in Season 1
Detection of RSV was done by PCR method by using any respiratory sample. The incidence of RSV PCR-positive respiratory illness during the RSV surveillance period was evaluated. The surveillance period was approximately 7 months and Season 1 was approximately 1 year.
Time frame: Day 14 after dosing through end of surveillance period (approximately 7 months)
Population: Per-protocol population: All participants in the ATP who were followed for qualifying symptoms for RSV until the end of the RSV surveillance period. Participants who met the primary endpoint criteria and were not followed until the end of the RSV surveillance period were also included in the per-protocol population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + IIV | Percentage of Participants Who Had a RSV Polymerase Chain Reaction (PCR)-Positive Respiratory Illness During the RSV Surveillance Period in Season 1 | 1.6 Percentage of Participants |
| MEDI7510 + IIV | Percentage of Participants Who Had a RSV Polymerase Chain Reaction (PCR)-Positive Respiratory Illness During the RSV Surveillance Period in Season 1 | 1.7 Percentage of Participants |
Secondary
Percentage of Participants Who Had a Strain-specific Post-dose Seroresponse to HAI Antibody
Seroresponse was defined as a \>= 4-fold rise of strain-specific HAI antibodies (H1N1, H3N2, B BRISBANE, and B PHUKET) from baseline. The Season 1 was approximately 1 year.
Time frame: Day 29 of Season 1
Population: Immunogenicity population for IIV: All participants in the ATP who had no major protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response to the influenza vaccine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + IIV | Percentage of Participants Who Had a Strain-specific Post-dose Seroresponse to HAI Antibody | H1N1 | 32.6 Percentage of Participants |
| Placebo + IIV | Percentage of Participants Who Had a Strain-specific Post-dose Seroresponse to HAI Antibody | B BRISBANE | 31.7 Percentage of Participants |
| Placebo + IIV | Percentage of Participants Who Had a Strain-specific Post-dose Seroresponse to HAI Antibody | H3N2 | 76.5 Percentage of Participants |
| Placebo + IIV | Percentage of Participants Who Had a Strain-specific Post-dose Seroresponse to HAI Antibody | B PHUKET | 33.0 Percentage of Participants |
| MEDI7510 + IIV | Percentage of Participants Who Had a Strain-specific Post-dose Seroresponse to HAI Antibody | H3N2 | 74.2 Percentage of Participants |
| MEDI7510 + IIV | Percentage of Participants Who Had a Strain-specific Post-dose Seroresponse to HAI Antibody | H1N1 | 32.4 Percentage of Participants |
| MEDI7510 + IIV | Percentage of Participants Who Had a Strain-specific Post-dose Seroresponse to HAI Antibody | B PHUKET | 30.2 Percentage of Participants |
| MEDI7510 + IIV | Percentage of Participants Who Had a Strain-specific Post-dose Seroresponse to HAI Antibody | B BRISBANE | 26.9 Percentage of Participants |
Secondary
Post-dose Geometric Mean Concentration (GMC) of Palivizumab Competitive Antibodies as Measured by a Palivizumab Competitive Enzyme Linked Immunosorbent Assay (cELISA)
Palivizumab cELISA assay was to be used to assess humoral immunity (HAI antibody titers) against RSV. GMC was to be calculated as: anti-log2 \[mean (log2 xi)\], where xi is an antibodies concentration of participants. The Season 1 was approximately 1 year.
Time frame: Day 29 and End of Season 1 (approximately 1 year)
Population: Data for this outcome measure were not collected as the study was terminated prematurely because the study did not meet its primary efficacy outcome measure.
Secondary
Post-dose Geometric Mean Fold Change of Palivizumab Competitive Antibodies as Measured by a Palivizumab cELISA
Palivizumab cELISA assay was to be used to assess humoral immunity (HAI antibody titers) against RSV. Geometric mean fold change was to be calculated as: anti-log2 \[mean (log2 yi)\], where yi is the post dose antibody concentration or T-cell count fold rise from baseline for each participant. The Season 1 was approximately 1 year.
Time frame: Day 29 and End of Season 1 (approximately 1 year)
Population: Data for this outcome measure were not collected as the study was terminated prematurely because the study did not meet its primary efficacy outcome measure.
Secondary
Post-dose Geometric Mean Fold Change of Serum Antibodies Against RSV by Microneutralization Assay
Microneutralization assay was to be used to assess humoral immunity (HAI antibody titers) against RSV. Geometric mean fold change was to be calculated as: anti-log2 \[mean (log2 yi)\], where yi is the post dose antibody concentration or T-cell count fold rise from baseline for each participant. The Season 1 was approximately 1 year.
Time frame: Day 29 and End of Season 1 (approximately 1 year)
Population: Data for this outcome measure were not collected as the study was terminated prematurely because the study did not meet its primary efficacy outcome measure.
Secondary
Post-dose Geometric Mean Fold Change of Strain-Specific HAI Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine
Geometric mean fold change was calculated as: anti-log2 \[mean (log2 yi)\], where yi is the post dose antibody concentration or T-cell count fold change from baseline for each participant. Geometric mean fold change of strain-specific HAI antibodies (H1N1, H3N2, B BRISBANE, and B PHUKET) were reported. The Season 1 was approximately 1 year.
Time frame: Day 29 of Season 1
Population: Immunogenicity population for IIV: All participants in the ATP who had no major protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response to the influenza vaccine.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Placebo + IIV | Post-dose Geometric Mean Fold Change of Strain-Specific HAI Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | H1N1 | 2.97 Fold Change |
| Placebo + IIV | Post-dose Geometric Mean Fold Change of Strain-Specific HAI Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | H3N2 | 8.42 Fold Change |
| Placebo + IIV | Post-dose Geometric Mean Fold Change of Strain-Specific HAI Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | B BRISBANE | 2.53 Fold Change |
| Placebo + IIV | Post-dose Geometric Mean Fold Change of Strain-Specific HAI Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | B PHUKET | 2.63 Fold Change |
| MEDI7510 + IIV | Post-dose Geometric Mean Fold Change of Strain-Specific HAI Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | B PHUKET | 2.40 Fold Change |
| MEDI7510 + IIV | Post-dose Geometric Mean Fold Change of Strain-Specific HAI Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | H1N1 | 2.78 Fold Change |
| MEDI7510 + IIV | Post-dose Geometric Mean Fold Change of Strain-Specific HAI Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | B BRISBANE | 2.24 Fold Change |
| MEDI7510 + IIV | Post-dose Geometric Mean Fold Change of Strain-Specific HAI Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine | H3N2 | 7.49 Fold Change |
Secondary
Post-dose GMTs of Serum Antibodies Against RSV by Microneutralization Assay
Microneutralization assay was to be used to assess humoral immunity (HAI antibody titers) against RSV. GMT was to be calculated as: anti-log2 \[mean (log2 xi)\], where xi is an antibodies concentration of participants. The Season 1 was approximately 1 year.
Time frame: Day 29 and End of Season 1 (approximately 1 year)
Population: Data for this outcome measure were not collected as the study was terminated prematurely because the study did not meet its primary efficacy outcome measure.