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

Phase 1

Completed

Conditions: Respiratory Syncytial Virus (RSV)

Interventions: Biological: MEDI7510
Biological: IIV

Registration Number: NCT02289820

Lead Sponsor: MedImmune LLC

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)

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 363

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MEDI7510 (120 mcg sF + 1 mcg GLA), Cohort 1	MEDI7510	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.
MEDI7510 (120 mcg sF + 5 mcg GLA), Cohort 3	MEDI7510	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.
Inactivated Influenza Vaccine (IIV)	IIV	Participants will receive a single dose of IIV by intramuscular injection in contralateral arms on Day 1.
MEDI7510 (120 mcg sF + 2.5 mcg GLA), Cohort 2	MEDI7510	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.
MEDI7510 (120 mcg sF + 2.5 mcg GLA), Cohort 2	IIV	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.
MEDI7510 (80 mcg sF + 2.5 mcg GLA), Cohort 4	MEDI7510	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Solicited Symptoms	Day 1 to Day 7	Solicited symptoms are events that are considered likely to occur post dosing and included the local reaction (pain, tenderness or soreness, redness, and swelling at the site of injection) to investigational product (IP) injection and systemic symptoms (fever greater than or equal to \[\>=\] 100.4°F \[\>=38°C\] by any route, headache, generalized muscle aches, and fatigue or tiredness) that might be related to IP injection. Solicited symptoms were not coded using Medical Dictionary for Regulatory Activities (MedDRA) and summarized regardless of whether or not they are treatment emergent. The percentage of participants with solicited symptoms were recorded during Days 1 (day of dosing) through 7.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)	From Day 1 to Day 29	An adverse event (AE) was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Treatment-emergent were the events between administration of study drug and including the follow-up period through Day 29. The AEs were summarized using the Medical Dictionary for Regulatory Activities version 18.1.
Percentage of Participants With Treatment-emergent Serious Adverse Events	From Day 1 to Day 361	A serious adverse event (SAE) was an AE resulting in any of following reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk), persistent or significant disability/incapacity, congenital anomaly, and a medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above.
Percentage of Participants With New Onset Chronic Diseases (NOCDs)	From Day 1 to Day 361	A NOCD was a newly diagnosed medical condition that is of a chronic, ongoing nature. It was observed after receiving study drug and was assessed by investigator as medically significant. All NOCDs were recorded from the time of dosing through the day of the last participant contact (Day 361 visit).
Percentage of Participants With Treatment-emergent Adverse Events of Special Interest (TEAESI)	From Day 1 to Day 361	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. Treatment emergent AESIs were collected from the time of dosing through the day of the last participant contact (Day 361 visit).

Secondary Outcome Measures

Name	Time	Method
Geometric Mean Concentrations of Serum Antibodies Against RSV by Anti F Immunoglobulin G (IgG) Assay	Baseline (Day 1), Day 29, 61, 91, 181, 271, and 361	Humoral immunogenicity samples were used to assess anti-F IgG antibodies measured using a 4-plex Meso Scale Discovery (MSD) platform assay. Results through Day 361 are presented.
Geometric Mean Titers (GMTs) of Serum Antibodies Against Respiratory Syncytial Virus (RSV) by RSV A Microneutralization Assay	Baseline (Day 1), Day 29, 61, 91, 181, 271, and 361	GMTs of serum antibodies against RSV, as assessed by the RSV A microneutralization assay at Baseline and the results through Day 361 were presented. Humoral immunogenicity samples was used to assess RSV A neutralizing antibody. Humoral immunity against RSV was assessed by a microneutralization assay for RSV A. Immunogenicity population is defined as all participants in ATP who had no protocol deviation judged to have the potential to interfere with generation or interpretation of an immune response.
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	Baseline (Day 1) and Day 8	The Geometric Mean Counts assessed by the ELISPOT assay for F protein-specific gamma interferon-producing T cells was performed using RSV F peptides. Cell-mediated immunity was assessed using an IFNγ ELISPOT assay to measure the T-cell responses to the RSV F peptide pool using thawed, cryopreserved peripheral blood mononuclear cell samples.
Percentage of Participants With Post-dose Seroresponse to RSV by Anti-F IgG Assay	Day 29	Seroresponse defined as a greater than or equal to (\>=) 3-fold rise from baseline. Humoral immunity against RSV was assessed by an Anti-F IgG assay derived from the RSV-specific 4-plex MSD assay.
Geometric Mean Fold Rises (GMFRs) of Serum Antibodies Against RSV by RSV A Microneutralization Assay	Day 29, 61, 91, 181, 271, and 361	GMFRs of serum antibodies against RSV, as assessed by the RSV A microneutralization assay from Baseline line through Day 361 were presented. Humoral immunogenicity samples was used to assess RSV A neutralizing antibody. Humoral immunity against RSV was assessed by a microneutralization assay for RSV A.
GMFRs of Cellular Immune Response Against RSV by RSV F IFNγ ELISPOT Assay	Day 8	The GMFRs assessed by the ELISPOT assay for F protein-specific gamma interferon-producing T cells was performed using RSV F peptides. Cell-mediated immunity was assessed using an IFNγ ELISPOT assay to measure the T-cell responses to the RSV F peptide pool using thawed, cryopreserved peripheral blood mononuclear cell samples
Percentage of Participants With Post-dose Seroresponse to RSV by RSV A Microneutralization Assay	Day 29	Seroresponse defined as a greater than or equal to (\>=) 3-fold rise in titer from baseline. Humoral immunogenicity samples was used to assess RSV A neutralizing antibody. Humoral immunity against RSV was assessed by a microneutralization assay for RSV A.
GMFRs of Serum Antibodies Against RSV by Anti F IgG Assay	Day 29, 61, 91, 181, 271, and 361	The Anti F IgG antibodies were derived from the RSV-specific 4-plex MSD assay developed on the Meso Scale discovery platform. Humoral immunogenicity samples were used to assess anti-F IgG antibodies measured using a 4-plex Meso Scale Discovery (MSD) platform assay. Results through Day 361 are presented.
Ratios of GMTs and GMFRs of Hemagglutination Inhibition (HAI) Antibodies	Day 29	The ratio of post-dose HAI antibody GMTs and GMFRs in the IIV group and the MEDI7510 plus IIV group was provided by strain and by cohort for Cohorts 2 and 3 to check the effect of MEDI7510 on IIV when administered together. Humoral immunity against influenza consisting of HAI antibody to strains antigenically matched to those contained in the IIV was assessed on Day 29 by each strain (H1N1, H3N2, B/Yamagata).
Percentage of Participants With Post-dose Cell-mediated Immune Response to RSV F by RSV F Peptide Pool IFNγ ELISPOT	Day 8	Seroresponse defined as a greater than or equal to (\>=) 3-fold rise from baseline. The Cell-mediated immunity was assessed using an IFNγ ELISPOT assay to measure the T-cell responses to the RSV F peptide pool using thawed, cryopreserved peripheral blood mononuclear cell samples.