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

NCT ID: NCT02289820

Last Updated: 2018-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 363 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-05
• Study Completion Date: 2016-02-24

Brief Summary

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.

Detailed Description

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)

Conditions

Respiratory Syncytial Virus (RSV)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

MEDI7510 (120 mcg sF + 1 mcg GLA), Cohort 1

Participants will receive a single dose of MEDI7510 (120 microgram \[mcg\] respiratory syncytial virus \[RSV\] soluble fusion protein \[sF\] plus 1.0 mcg glucopyranosyl lipid A in 2% volume per volume stable emulsion) administered by intramuscular (IM) injection on Day 1.

Group Type: EXPERIMENTAL

MEDI7510

Intervention Type: BIOLOGICAL

RSV sF antigen plus adjuvant

MEDI7510 (120 mcg sF + 2.5 mcg GLA), Cohort 2

Participants will receive a single dose of MEDI7510 (120 mcg RSV sF plus 2.5 mcg glucopyranosyl lipid A in 2% volume per volume stable emulsion) plus IIV or MEDI7510 plus placebo administered by IM injection in contralateral arms on Day 1.

Group Type: EXPERIMENTAL

MEDI7510

Intervention Type: BIOLOGICAL

RSV sF antigen plus adjuvant

IIV

Intervention Type: BIOLOGICAL

Marketed Inactivated Influenza Vaccine

MEDI7510 (120 mcg sF + 5 mcg GLA), Cohort 3

Participants will receive a single dose of MEDI7510 (120 mcg RSV sF plus 5.0 mcg glucopyranosyl lipid A in 2% volume per volume stable emulsion) plus IIV or MEDI7510 plus placebo administered by IM injection in contralateral arms on Day 1.

Group Type: EXPERIMENTAL

MEDI7510

Intervention Type: BIOLOGICAL

RSV sF antigen plus adjuvant

MEDI7510 (80 mcg sF + 2.5 mcg GLA), Cohort 4

Participants will receive a single dose of MEDI7510 (80 mcg RSV sF plus 2.5 mcg glucopyranosyl lipid A in 2% volume per volume stable emulsion) administered by IM injection on Day 1.

Group Type: EXPERIMENTAL

MEDI7510

Intervention Type: BIOLOGICAL

RSV sF antigen plus adjuvant

Inactivated Influenza Vaccine (IIV)

Participants will receive a single dose of IIV by intramuscular injection in contralateral arms on Day 1.

Group Type: ACTIVE_COMPARATOR

IIV

Intervention Type: BIOLOGICAL

Marketed Inactivated Influenza Vaccine

Interventions

MEDI7510

RSV sF antigen plus adjuvant

Intervention Type: BIOLOGICAL

IIV

Marketed Inactivated Influenza Vaccine

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

MedImmune LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Judith Falloon, MD

Role: STUDY_DIRECTOR

MedImmune LLC

Eric Sheldon, MD

Role: PRINCIPAL_INVESTIGATOR

Miami Research Associates

Craig Curtis, MD

Role: PRINCIPAL_INVESTIGATOR

Compass Research

John Ervin, MD

Role: PRINCIPAL_INVESTIGATOR

The Center for Pharmaceutical Research

Wayne Harper, MD

Role: PRINCIPAL_INVESTIGATOR

Wake Research Associates

H. Keipp Talbot, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Research Site

Orlando, Florida, United States

Research Site

South Miami, Florida, United States

Research Site

Kansas City, Missouri, United States

Research Site

Raleigh, North Carolina, United States

Research Site

Nashville, Tennessee, United States

Countries

United States

References

Chang LA, Phung E, Crank MC, Morabito KM, Villafana T, Dubovsky F, Falloon J, Esser MT, Lin BC, Chen GL, Graham BS, Ruckwardt TJ. A prefusion-stabilized RSV F subunit vaccine elicits B cell responses with greater breadth and potency than a postfusion F vaccine. Sci Transl Med. 2022 Dec 21;14(676):eade0424. doi: 10.1126/scitranslmed.ade0424. Epub 2022 Dec 21.

Reference Type: DERIVED

PMID: 36542692 (View on PubMed)

Falloon J, Talbot HK, Curtis C, Ervin J, Krieger D, Dubovsky F, Takas T, Yu J, Yu L, Lambert SL, Villafana T, Esser MT. Dose Selection for an Adjuvanted Respiratory Syncytial Virus F Protein Vaccine for Older Adults Based on Humoral and Cellular Immune Responses. Clin Vaccine Immunol. 2017 Sep 5;24(9):e00157-17. doi: 10.1128/CVI.00157-17. Print 2017 Sep.

Reference Type: DERIVED

PMID: 28679495 (View on PubMed)

Other Identifiers

D4420C00004

Identifier Type: -

Identifier Source: org_study_id