A Study to Evaluate the Safety and Immunogenicity of MEDI7510 in Older Adults

A Phase 1b Study to Evaluate the Safety and Immunogenicity of MEDI7510 in Older Adults

The goal of this study is to evaluate the safety, tolerability and immunogenicity of ascending doses of adjuvant in combination with a single dosage level of RSV sF in adults 60 years or older who are healthy or who have stable, chronic underlying medical conditions. This study will also provide preliminary safety and immunogenicity data to support concurrent dosing of MEDI7510 with influenza vaccine (IIV), and to assess the safety of MEDI7510 at a dose previously assessed in the Phase 1a study.

A Phase 1b, double-blind, randomized, controlled cohort escalation study evaluating the safety, tolerability and immunogenicity of MEDI7510.

Approximately 264 subjects will be enrolled at approximately 5 study centers in the US and randomized by cohort (Cohort 1 [4:1]; Cohorts 2 and 3 [8:8:3]; Cohort 4 [5:1]) to receive a single intramuscular dose of 1 study vaccine (Cohorts 1 and 4) or a single intramuscular dose of each of 2 study vaccines (Cohorts 2 and 3) administered in contralateral arms.

Cohort 1: MEDI7510 formulation (n = 40) or IIV (n = 10) Cohort 2: MEDI7510 formulation and placebo (n = 40) or MEDI7510 formulation and IIV (n = 40) or placebo and IIV (n = 15) Cohort 3: MEDI7510 formulation and placebo (n = 40) or MEDI7510 formulation and IIV (n = 40) or placebo and IIV (n = 15) Cohort 4: MEDI7510 formulation (n = 20) or IIV (n = 4)

Inclusion Criteria:

• Age greater than or equal to 60 years
• Ambulatory or ambulatory with assistance (not institutionalized, bedridden, or homebound)
• Weight greater than 90 lbs
• Hemoglobin greater than or equal to 10.5 g/dL for women and greater than or equal to 11 g/dL for men
• Subject able to complete follow-up period of 360 days after dosing

Exclusion Criteria:

• History of allergy to: any component of the vaccine; IIV or intolerance of IIV; eggs in adulthood
• Receipt of seasonal flu shot within 60 days prior to dosing
• Any unstable acute or chronic medical condition, including one that has resulted in change in therapy (medication or other) in the 30 days prior to randomization or hospitalization in the previous year or might be predicted to result in hospitalization in the year after enrollment. Subjects with severe, untreated or uncontrolled underlying medical disease that might either compromise subject safety or affect the ability to assess safety of the investigational product are excluded. Medications taken on an as-needed basis are permitted to start or stop during the 30 days prior to randomization unless they are medications not previously taken by the subject
• Clinically significant abnormalities in screening laboratory assessments or screening ECG
• History of hepatitis B or hepatitis C infection
• History of Guillain-Barré syndrome
• Cognitive disorder such that informed consent cannot be obtained directly from the subject
• Previous vaccination against RSV
• History of or current autoimmune disorder
• Immunosuppression caused by disease, including human immunodeficiency virus (HIV) infection, or medications. Any oral prednisone dosing within 30 days of enrollment or planned dosing within the 360-day follow-up period would disqualify. Expected need for immunosuppressive medications during the 360-day follow-up period would disqualify
• History of splenectomy or of condition affecting splenic function (eg, hemoglobinopathy)
• History of cancer within preceding 5 years other than treated non-melanoma skin cancer
• Body Mass Index 40 or higher
• Receipt of any nonstudy vaccine within 30 days prior to study dosing or expected receipt of nonstudy vaccine within 30 days after study dosing
• Receipt of any investigational product in the 90 days prior to randomization or expected receipt of investigational product 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 investigational product 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)
• Expected receipt of antipyretic or analgesic medication on a daily or every other day basis from randomization through 72 hours after receipt of IP (Note: A daily dose of aspirin is not considered a contraindication to enrollment.)
• Subjects who have significant scarring, tattoos, abrasions, cuts, or infections over the deltoid region of both arms that, in the investigators opinion, could interfere with evaluation of injection site local reactions
• Concurrent enrollment in another clinical study that involves any invasive clinical procedure, including phlebotomy
• History of alcohol or drug abuse or psychiatric disorder that, in the investigators opinion, would affect the subject's safety or compliance with study
• Employees of individuals directly involved with the conduct of the study, individuals who themselves are involved with the conduct of the study, or immediate family members of such individuals