A Study to Evaluate the Safety of the Respiratory Syncytial Virus Vaccine MEDI7510 in Older Adults

Phase 1

Completed

Conditions: Respiratory Syncytial Virus (RSV)

Interventions: Biological: MEDI7510 (20 mcg RSV sF)
Biological: RSV sF 50 mcg
Biological: Placebo
Biological: RSV sF 80 mcg
Biological: RSV sF 20 mcg
Biological: MEDI7510 (50 mcg RSV sF)
Biological: MEDI7510 (80 mcg RSV sF)

Registration Number: NCT02115815

Lead Sponsor: MedImmune LLC

Brief Summary: The purpose of this study is to determine if the administration of single ascending intramuscular doses of the RSV sF antigen or MEDI7510 will be safe and well tolerated in adults 60 years or older who are healthy or who have stable, chronic underlying medical conditions.

Detailed Description: A phase 1a, first time in human, double-blind, randomized, placebo-controlled, cohort escalation study evaluating the safety and tolerability of a single ascending intramuscular dose of RSV sF or MEDI7510 or placebo.

Approximately 146 participants will be enrolled at 3 US study centers and randomized in a 5:1 ratio by cohort as described below:

Cohort 1: RSV sF 20 microgram (mcg) (n=20) or placebo (n=4) Cohort 1a: MEDI7510 (20 mcg RSV sF with 2.5 mcg glucopyranosyl lipid A (GLA) + 2% weight per volume stable emulsion (n=20) or placebo (n=4) Cohort 2: RSV sF 50 mcg (n=20) or placebo (n=4) Cohort 2a: MEDI7510 (50 mcg RSV sF with 2.5 mcg glucopyranosyl lipid A (GLA) + 2% weight per volume stable emulsion (n=20) or placebo (n=4) Cohort 3: 80 mcg RSV sF (n=20) or placebo (n=4) Cohort 3a: MEDI7510 (80 mcg RSV sF with 2.5 mcg glucopyranosyl lipid A (GLA) + 2% weight per volume stable emulsion (n=20) or placebo (n=4)

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 246

Inclusion Criteria

Age greater than or equal to 60 years
Written informed consent and any locally required authorization obtained prior to any protocol related procedures
Ambulatory or ambulatory with assistance (not institutionalized, bedridden, or homebound
Weight at or above 110 Pounds (lbs)
Hemoglobin within normal range for age and gender

Exclusion Criteria

History of allergy to any component of the vaccine
Pregnancy or potential to become pregnant during the study. Females who have had a menstrual period within the 12 months prior to study enrollment or are undergoing any fertility treatment or who plan to undergo fertility treatments during the study period are excluded
Any unstable 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. Participant with severe, untreated or uncontrolled underlying medical disease that might either compromise participant safety or affect the ability to assess safety of the investigational product are excluded
Clinically significant abnormalities in Screening laboratory assessments or Screening electrocardiogram (ECG)
History of hepatitis B or hepatitis C infection
Cognitive disorder such that informed consent cannot be obtained directly from the participant
Previous vaccination against respiratory syncytial virus (RSV)
History of allergy to eggs in adulthood
History of or current autoimmune disorder
Immunosuppression caused by disease, including human immunodeficiency virus (HIV), or medications. Any oral prednisone dosing within 30 days of enrollment or planned dosing within the 360-day follow-up period would disqualify.
History of splenectomy or of condition affecting splenic function
History of cancer within preceding 5 years other than treated non-melanoma skin cancer
Body Mass Index 40 or higher
Significant infection or other acute illness, including fever over 100 fahrenheit (F) on the day prior to or day of randomization
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
History of thrombocytopenia or bleeding disorder or use of anticoagulants. Participants receiving drugs with anti-platelet activity such as nonsteroidal antiinflammatory drugs, clopidogrel or aspirin are not excluded
Expected receipt of antipyretic or analgesic medication on a daily or every other day basis from randomization through 72 hours after receipt of investigational product (IP) [a daily dose of 163 milligram (mg) or higher is not considered a contraindication to enrollment]
Participants who have significant scarring, tattoos, abrasions, cuts, or infections over the deltoid region of both arms that, in the principle investigator's (PI) 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 PI's opinion would affect the participants 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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MEDI7510 (20 mcg RSV sF)	MEDI7510 (20 mcg RSV sF)	Participants will receive single dose of MEDI7510 (20 mcg RSV sF with 2.5 mcg glucopyranosyl lipid A \[GLA\] + 2% weight per volume stable emulsion) by intramuscular injection on Day 1.
RSV sF 50 mcg	RSV sF 50 mcg	Participants will receive single dose of 50 mcg RSV sF by intramuscular injection on Day 1.
Placebo	Placebo	Sterile saline for human use from commercial source, liquid
RSV sF 80 mcg	RSV sF 80 mcg	Participants will receive single dose of 80 mcg RSV sF by intramuscular injection on Day 1.
RSV sF 20 mcg	RSV sF 20 mcg	Participants will receive single dose of 20 mcg RSV sF by intramuscular injection on Day 1.
MEDI7510 (50 mcg RSV sF)	MEDI7510 (50 mcg RSV sF)	Participants will receive single dose of MEDI7510 (50 mcg RSV sF with 2.5 mcg GLA + 2% weight per volume stable emulsion) by intramuscular injection on Day 1.
MEDI7510 (80 mcg RSV sF)	MEDI7510 (80 mcg RSV sF)	Participants will receive a single dose of MEDI7510 (80 mcg RSV sF with 2.5 mcg GLA + 2% weight per volume stable emulsion) by intramuscular injection on Day 1.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Solicited Symptoms	Day 1 to 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 greater than or equal to (\>=) 100.4 degrees F by any route from Day 1 to Day 7.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)	From Day 1 to Day 28	An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received investigational product. A 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 product and Day 361 that were absent before treatment or that worsened relative to pretreatment 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)	From Day 1 to Day 361	An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received investigational product. A 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 product and Day 361 that were absent before treatment or that worsened relative to pretreatment state. An AESI was one of scientific and medical interest specific to understanding of study product 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 investigational product and was assessed by investigator as medically significant.

Secondary Outcome Measures

Name	Time	Method
Post-dose Geometric Mean Titers (GMTs) From Baseline of Serum Antibodies Against Respiratory Syncytial Virus (RSV) by RSV A Microneutralization Assay	Baseline (Day 1), Day 29, 61, 91, 181, 271 and 361	RSV neutralizing antibody titers were measured using green fluorescent protein tagged RSV A 2
Post-dose Geometric Mean Fold Rises (GMFRs) From Baseline of Serum Antibodies Against Respiratory Syncytial Virus (RSV) by RSV A Microneutralization Assay	Day 29, 61, 91, 181, 271 and 361	RSV neutralizing antibody titers were measured using green fluorescent protein tagged RSV A 2.
Percentage of Participants Who Experience a Post-dose Seroresponse to Respiratory Syncytial Virus (RSV) by RSV A Microneutralization Assay	Day 29	Seroresponse defined as a greater than or equal to (\>=) 4-fold rise from baseline.
Post-dose Geometric Mean Titers (GMTs) From Baseline of Serum Antibodies Against Respiratory Syncytial Virus (RSV) by Anti-Fusion Protein (F) Immunoglobulin G (IgG) Assay	Baseline (Day 1), Day 29, 61, 91, 181, 271 and 361	Anti F IgG antibodies were determined by a multiplex IgG assay developed on the Meso Scale discovery platform.
Post-dose Geometric Mean Fold Rises (GMFRs) From Baseline of Serum Antibodies Against Respiratory Syncytial Virus (RSV) by Anti-Fusion Protein (F) Immunoglobulin G (IgG) Assay	Day 29, 61, 91, 181, 271 and 361	Anti F IgG antibodies were determined by a multiplex IgG assay developed on the Meso Scale discovery platform.
Percentage of Participants Who Experience a Post-dose Seroresponse to Respiratory Syncytial Virus (RSV) by Anti-Fusion Protein (F) Immunoglobulin G (IgG) Assay	Day 29	Seroresponse defined as a greater than or equal to (\>=) 4-fold rise from baseline.
Post-dose Geometric Mean Counts (GMCs) From Baseline of T Cell Response Against Respiratory Syncytial Virus (RSV) by RSV F Enzyme-Linked Immunospot (ELISPOT)	Baseline (Day 1), Day 8 and 29	The ELISPOT assay for F protein-specific gamma interferon-producing T cells was performed using RSV F peptides.
Post-dose Geometric Mean Fold Rises (GMFRs) of T Cell Response Against Respiratory Syncytial Virus (RSV) by RSV F Enzyme-Linked Immunospot (ELISPOT)	Day 8 and 29	The ELISPOT assay for F protein-specific gamma interferon-producing T cells was performed using RSV F peptides.
Percentage of Participants Who Experience a Post-dose 3-fold Cell-mediated Immune Response to RSV F on Day 8	Day 8	Seroresponse defined as a greater than or equal to (\>=) 3-fold rise from baseline

Trial Locations

Locations (3): Accelovance, Inc
🇺🇸
Rockville, Maryland, United States
Miami Research Associates
🇺🇸
Miami, Florida, United States
Compass Research
🇺🇸
Orlando, Florida, United States