Clinical trial NCT02115815: A Study to Evaluate the Safety of the Respiratory Syncytial Virus Vaccine MEDI7510 in Older Adults
Official title: A Phase 1a Study to Evaluate the Safety of the Respiratory Syncytial Virus Vaccine MEDI7510 in Older Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Respiratory Syncytial Virus (RSV)
Keywords: Respiratory Syncytial Virus (RSV)
MEDI7510
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2014-04-16
Enrollment: 246
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: 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)

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Solicited Symptoms
timeFrame: Day 1 to Day 7
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: From Day 1 to Day 28
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: From Day 1 to Day 361
Secondary outcomes:
measure: Post-dose Geometric Mean Titers (GMTs) From Baseline of Serum Antibodies Against Respiratory Syncytial Virus (RSV) by RSV A Microneutralization Assay
timeFrame: Baseline (Day 1), Day 29, 61, 91, 181, 271 and 361
measure: Post-dose Geometric Mean Fold Rises (GMFRs) From Baseline of Serum Antibodies Against Respiratory Syncytial Virus (RSV) by RSV A Microneutralization Assay
timeFrame: Day 29, 61, 91, 181, 271 and 361
measure: Percentage of Participants Who Experience a Post-dose Seroresponse to Respiratory Syncytial Virus (RSV) by RSV A Microneutralization Assay
timeFrame: Day 29
measure: 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
timeFrame: Baseline (Day 1), Day 29, 61, 91, 181, 271 and 361
measure: 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
timeFrame: Day 29, 61, 91, 181, 271 and 361
measure: Percentage of Participants Who Experience a Post-dose Seroresponse to Respiratory Syncytial Virus (RSV) by Anti-Fusion Protein (F) Immunoglobulin G (IgG) Assay
timeFrame: Day 29
measure: Post-dose Geometric Mean Counts (GMCs) From Baseline of T Cell Response Against Respiratory Syncytial Virus (RSV) by RSV F Enzyme-Linked Immunospot (ELISPOT)
timeFrame: Baseline (Day 1), Day 8 and 29
measure: Post-dose Geometric Mean Fold Rises (GMFRs) of T Cell Response Against Respiratory Syncytial Virus (RSV) by RSV F Enzyme-Linked Immunospot (ELISPOT)
timeFrame: Day 8 and 29
measure: Percentage of Participants Who Experience a Post-dose 3-fold Cell-mediated Immune Response to RSV F on Day 8
timeFrame: Day 8
Other outcomes:
Locations:
city: Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Orlando
country: United States
facility: Compass Research
state: Florida
city: Rockville
country: United States
facility: Accelovance, Inc
state: Maryland
Study officials:
affiliation: Miami Research Associates
name: Eric Sheldon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Compass Research
name: Craig Curtis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Accelovance
name: Steven Bart, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: MedImmune LLC
name: Judith Falloon, MD
role: STUDY_DIRECTOR
References:
citation: Falloon J, Ji F, Curtis C, Bart S, Sheldon E, Krieger D, Dubovsky F, Lambert S, Takas T, Villafana T, Esser MT. A phase 1a, first-in-human, randomized study of a respiratory syncytial virus F protein vaccine with and without a toll-like receptor-4 agonist and stable emulsion adjuvant. Vaccine. 2016 May 27;34(25):2847-54. doi: 10.1016/j.vaccine.2016.04.002. Epub 2016 Apr 19.