Clinical trial NCT02508194: A Study to Evaluate the Efficacy of MEDI7510 in Older Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Respiratory Syncytial Virus
Keywords: RSV
Older adults
MEDI7510
Vaccine
Efficacy
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2015-07-24
Enrollment: 1900
Sex: ALL
Minimum age (years): 60
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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).

Primary outcomes:
measure: 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
timeFrame: Day 14 after dosing through end of surveillance period (approximately 7 months)
Secondary outcomes:
measure: Percentage of Participants Who Had a RSV Polymerase Chain Reaction (PCR)-Positive Respiratory Illness During the RSV Surveillance Period in Season 1
timeFrame: Day 14 after dosing through end of surveillance period (approximately 7 months)
measure: Geometric Mean Responses (GMRs) of Serum Antibodies Concentration Against RSV by Anti-Fusion Protein (F) Immunoglobulin G (IgG) Assay
timeFrame: Day 1, Day 29, and End of Season 1 (approximately 1 year)
measure: Geometric Mean Fold Change of Serum Antibodies Concentration Against RSV by Anti-F IgG Assay
timeFrame: Day 29 and End of Season 1 (approximately 1 year)
measure: Percentage of Participants Who Had a Post-dose Seroresponse to RSV as Measured by Anti-F IgG Assay
timeFrame: Day 29 and End of Season 1 (approximately 1 year)
measure: Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition (HAI) Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine
timeFrame: Day 1 (post-dose) and Day 29 of Season 1
measure: Post-dose Geometric Mean Fold Change of Strain-Specific HAI Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine
timeFrame: Day 29 of Season 1
measure: Percentage of Participants Who Had a Strain-specific Post-dose Seroresponse to HAI Antibody
timeFrame: Day 29 of Season 1
measure: Post-dose GMTs of Serum Antibodies Against RSV by Microneutralization Assay
timeFrame: Day 29 and End of Season 1 (approximately 1 year)
measure: Post-dose Geometric Mean Fold Change of Serum Antibodies Against RSV by Microneutralization Assay
timeFrame: Day 29 and End of Season 1 (approximately 1 year)
measure: Percentage of Participants Who Had a Post-dose Seroresponse to RSV by Microneutralization Assay
timeFrame: Day 29 and End of Season 1 (approximately 1 year)
measure: Post-dose Geometric Mean Concentration (GMC) of Palivizumab Competitive Antibodies as Measured by a Palivizumab Competitive Enzyme Linked Immunosorbent Assay (cELISA)
timeFrame: Day 29 and End of Season 1 (approximately 1 year)
measure: Post-dose Geometric Mean Fold Change of Palivizumab Competitive Antibodies as Measured by a Palivizumab cELISA
timeFrame: Day 29 and End of Season 1 (approximately 1 year)
measure: Percentage of Participants Who Had a Post-dose Seroresponse to RSV as Measured by a Palivizumab cELISA
timeFrame: Day 29 and End of Season 1 (approximately 1 year)
measure: Number of Participants With Any Solicited Symptoms
timeFrame: Day 1 (post-dose) through Day 7
measure: Number of Participants With Treatment-Emergent Adverse Events
timeFrame: Day 1 (post-dose) through Day 29
measure: 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)
timeFrame: Day 1 (post-dose) through end of Season 1 (approximately 1 year)
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Littleton
country: United States
facility: Research Site
state: Colorado
city: Lady Lake
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Savannah
country: United States
facility: Research Site
state: Georgia
city: Champaign
country: United States
facility: Research Site
state: Illinois
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Council Bluffs
country: United States
facility: Research Site
state: Iowa
city: Augusta
country: United States
facility: Research Site
state: Kansas
city: Wichita
country: United States
facility: Research Site
state: Kansas
city: Edina
country: United States
facility: Research Site
state: Minnesota
city: Cincinnati
country: United States
facility: Research Site
state: Missouri
city: Kansas City
country: United States
facility: Research Site
state: Missouri
city: Bellevue
country: United States
facility: Research Site
state: Nebraska
city: Norfolk
country: United States
facility: Research Site
state: Nebraska
city: Omaha
country: United States
facility: Research Site
state: Nebraska
city: Rochester
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Hickory
country: United States
facility: Research Site
state: North Carolina
city: Raleigh
country: United States
facility: Research Site
state: North Carolina
city: Rocky Mount
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Akron
country: United States
facility: Research Site
state: Ohio
city: Dakota Dunes
country: United States
facility: Research Site
state: South Dakota
city: Knoxville
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Murray
country: United States
facility: Research Site
state: Utah
city: Brampton
country: Canada
facility: Research Site
state: Ontario
city: London
country: Canada
facility: Research Site
state: Ontario
city: Newmarket
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Quebec
country: Canada
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Temuco
country: Chile
facility: Research Site
city: Paide
country: Estonia
facility: Research Site
city: Tallinn
country: Estonia
facility: Research Site
city: Tallinn
country: Estonia
facility: Research Site
city: Tallinn
country: Estonia
facility: Research Site
city: Daugavpils
country: Latvia
facility: Research Site
city: Jelgava
country: Latvia
facility: Research Site
city: Kuldiga
country: Latvia
facility: Research Site
city: Kaunas
country: Lithuania
facility: Research Site
city: Kaunas
country: Lithuania
facility: Research Site
city: Kaunas
country: Lithuania
facility: Research Site
city: Vilnius
country: Lithuania
facility: Research Site
city: Vilnius
country: Lithuania
facility: Research Site
city: Bellville
country: South Africa
facility: Research Site
city: Bloemfontein
country: South Africa
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Krugersdorp
country: South Africa
facility: Research Site
city: Pretoria
country: South Africa
facility: Research Site
city: Somerset West
country: South Africa
facility: Research Site
Study officials:
References:
citation: Falloon J, Yu J, Esser MT, Villafana T, Yu L, Dubovsky F, Takas T, Levin MJ, Falsey AR. An Adjuvanted, Postfusion F Protein-Based Vaccine Did Not Prevent Respiratory Syncytial Virus Illness in Older Adults. J Infect Dis. 2017 Dec 12;216(11):1362-1370. doi: 10.1093/infdis/jix503.