Clinical trial NCT02289820: A Study to Evaluate the Safety and Immunogenicity of MEDI7510 in Older Adults
Official title: A Phase 1b Study to Evaluate the Safety and Immunogenicity of MEDI7510 in Older Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Respiratory Syncytial Virus (RSV)
Keywords: RSV
Older adults
MEDI7510
Vaccine
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2014-11-13
Enrollment: 363
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 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)

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

Primary outcomes:
measure: Percentage of Participants With Solicited Symptoms
timeFrame: Day 1 to Day 7
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From Day 1 to Day 29
measure: Percentage of Participants With Treatment-emergent Serious Adverse Events
timeFrame: From Day 1 to Day 361
measure: Percentage of Participants With New Onset Chronic Diseases (NOCDs)
timeFrame: From Day 1 to Day 361
measure: Percentage of Participants With Treatment-emergent Adverse Events of Special Interest (TEAESI)
timeFrame: From Day 1 to Day 361
Secondary outcomes:
measure: Geometric Mean Titers (GMTs) 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: Geometric Mean Fold Rises (GMFRs) of Serum Antibodies Against RSV by RSV A Microneutralization Assay
timeFrame: Day 29, 61, 91, 181, 271, and 361
measure: Percentage of Participants With Post-dose Seroresponse to RSV by RSV A Microneutralization Assay
timeFrame: Day 29
measure: Geometric Mean Concentrations of Serum Antibodies Against RSV by Anti F Immunoglobulin G (IgG) Assay
timeFrame: Baseline (Day 1), Day 29, 61, 91, 181, 271, and 361
measure: GMFRs of Serum Antibodies Against RSV by Anti F IgG Assay
timeFrame: Day 29, 61, 91, 181, 271, and 361
measure: Percentage of Participants With Post-dose Seroresponse to RSV by Anti-F IgG Assay
timeFrame: Day 29
measure: Ratios of GMTs and GMFRs of Hemagglutination Inhibition (HAI) Antibodies
timeFrame: Day 29
measure: Geometric Mean Counts of Cellular Immune Response Against RSV by Respiratory Syncytial Virus Fusion Protein (RSV F) Interferon Gamma (IFNγ) Enzyme-linked Immunosorbent Spot (ELISPOT) Assay
timeFrame: Baseline (Day 1) and Day 8
measure: GMFRs of Cellular Immune Response Against RSV by RSV F IFNγ ELISPOT Assay
timeFrame: Day 8
measure: Percentage of Participants With Post-dose Cell-mediated Immune Response to RSV F by RSV F Peptide Pool IFNγ ELISPOT
timeFrame: Day 8
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Research Site
state: Florida
city: South Miami
country: United States
facility: Research Site
state: Florida
city: Kansas City
country: United States
facility: Research Site
state: Missouri
city: Raleigh
country: United States
facility: Research Site
state: North Carolina
city: Nashville
country: United States
facility: Research Site
state: Tennessee
Study officials:
affiliation: MedImmune LLC
name: Judith Falloon, MD
role: STUDY_DIRECTOR
affiliation: Miami Research Associates
name: Eric Sheldon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Compass Research
name: Craig Curtis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Center for Pharmaceutical Research
name: John Ervin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wake Research Associates
name: Wayne Harper, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University Medical Center
name: H. Keipp Talbot, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.