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

• ClinicalTrials.gov Identifier: NCT02115815
• Recruitment Status: Completed
• First Posted: April 16, 2014
• Results First Posted: October 21, 2016
• Last Update Posted: October 21, 2016
• Sponsor: MedImmune LLC
• Information provided by (Responsible Party): MedImmune LLC

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Respiratory Syncytial Virus (RSV)	Biological: Placebo; Biological: RSV sF 20 mcg; Biological: MEDI7510 (20 mcg RSV sF); Biological: RSV sF 50 mcg; Biological: MEDI7510 (50 mcg RSV sF); Biological: RSV sF 80 mcg; Biological: MEDI7510 (80 mcg RSV sF)	Phase 1

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)

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 246 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Phase 1a Study to Evaluate the Safety of the Respiratory Syncytial Virus Vaccine MEDI7510 in Older Adults
• Study Start Date: April 2014
• Actual Primary Completion Date: June 2015
• Actual Study Completion Date: June 2015

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Sterile saline for human use from commercial source, liquid	Biological: Placebo; Participants will receive placebo (sterile saline for human use from commercial source liquid) on Day 1.
Experimental: RSV sF 20 mcg; Participants will receive single dose of 20 mcg RSV sF by intramuscular injection on Day 1.	Biological: RSV sF 20 mcg; Participants will receive single dose of 20 mcg RSV sF by intramuscular injection on Day 1.
Experimental: 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.	Biological: MEDI7510 (20 mcg RSV sF); Participants will receive single dose of MEDI7510 containing 20 mcg RSV sF by intramuscular injection on Day 1.
Experimental: RSV sF 50 mcg; Participants will receive single dose of 50 mcg RSV sF by intramuscular injection on Day 1.	Biological: RSV sF 50 mcg; Participants will receive single dose of 50 mcg RSV sF by intramuscular injection on Day 1.
Experimental: 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.	Biological: MEDI7510 (50 mcg RSV sF); Participants will receive single dose of MEDI7510 containing 50 mcg RSV sF by intramuscular injection on Day 1.
Experimental: RSV sF 80 mcg; Participants will receive single dose of 80 mcg RSV sF by intramuscular injection on Day 1.	Biological: RSV sF 80 mcg; Participants will receive single dose of 80 mcg RSV sF by intramuscular injection on Day 1.
Experimental: 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.	Biological: MEDI7510 (80 mcg RSV sF); Participants will receive single dose of MEDI7510 containing 80 mcg RSV sF by intramuscular injection on Day 1.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Solicited Symptoms [ Time Frame: 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.
2. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [ Time Frame: 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.
3. 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) [ Time Frame: 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 :

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

Eligibility Criteria

• Ages Eligible for Study: 60 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

United States, Florida

Miami Research Associates

Miami, Florida, United States, 33143

Compass Research

Orlando, Florida, United States, 32806

United States, Maryland

Accelovance, Inc

Rockville, Maryland, United States, 20850

Sponsors and Collaborators

MedImmune LLC

Investigators

• Principal Investigator: Eric Sheldon, MD; Miami Research Associates
• Principal Investigator: Craig Curtis, MD; Compass Research
• Principal Investigator: Steven Bart, MD; Accelovance
• Study Director: Judith Falloon, MD; MedImmune LLC

More Information

Additional Information:

CD-VA-MEDI7510-1134 Redacted Protocol 

Publications of Results:

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.

• Responsible Party: MedImmune LLC
• ClinicalTrials.gov Identifier: NCT02115815
• Other Study ID Numbers: CD-VA-MEDI7510-1134; BB-IND 15947 ( Other Identifier: US FDA )
• First Posted: April 16, 2014
• Results First Posted: October 21, 2016
• Last Update Posted: October 21, 2016
• Last Verified: August 2016

Keywords provided by MedImmune LLC:

Respiratory Syncytial Virus (RSV); MEDI7510

Additional relevant MeSH terms:

Virus Diseases; Infections