A Study to Evaluate the Efficacy of MEDI7510 in Older Adults

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 2b Randomized, Double-blind Study to Evaluate the Efficacy of MEDI7510 for the Prevention of Acute Respiratory Syncytial Virus-associated Respiratory Illness in Older Adults

Conditions
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Respiratory Syncytial Virus

Intervention / Treatment
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* Biological: MEDI7510
* Biological: IIV
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Placebo + Inactivated Influenza Vaccine (IIV)<br>Participants received a single intramuscular (IM) injection of placebo (matched with MEDI7510) in one arm and single IM injection of (IIV) in the contralateral arm. | Biological: IIV<br>* Marketed Inactivated Influenza Vaccine<br>Other: Placebo<br>* Sterile Saline<br>|
| Experimental: MEDI7510 + IIV<br>Participants received a single IM injection of MEDI7510 in one arm and single IM injection of IIV in the contralateral arm. | Biological: MEDI7510<br>* RSV soluble fusion protein (sF) antigen plus glucopyranosyl lipid A in stable emulsion (GLA-SE) adjuvant<br>Biological: IIV<br>* Marketed Inactivated Influenza Vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 14 after dosing through end of surveillance period (approximately 7 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 14 after dosing through end of surveillance period (approximately 7 months) | 
| 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. | Day 1, Day 29, and End of Season 1 (approximately 1 year) | 
| 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. | Day 29 and End of Season 1 (approximately 1 year) | 
| 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. | Day 29 and End of Season 1 (approximately 1 year) | 
| 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. | Day 1 (post-dose) and Day 29 of Season 1 | 
| 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. | Day 29 of Season 1 | 
| 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. | Day 29 of Season 1 | 
| 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. | Day 29 and End of Season 1 (approximately 1 year) | 
| 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. | Day 29 and End of Season 1 (approximately 1 year) | 
| 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. | Day 29 and End of Season 1 (approximately 1 year) | 
| 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. | Day 29 and End of Season 1 (approximately 1 year) | 
| 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. | Day 29 and End of Season 1 (approximately 1 year) | 
| 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. | Day 29 and End of Season 1 (approximately 1 year) | 
| 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. | Day 1 (post-dose) through Day 7 | 
| 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. | Day 1 (post-dose) through Day 29 | 
| 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. | Day 1 (post-dose) through end of Season 1 (approximately 1 year) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Older adults, RSV, MEDI7510, Vaccine, Efficacy