Safety, Tolerability, and Immunogenicity of a Single Dose of Merck 0657nI Staphylococcus Aureus Vaccine With or Without Merck Aluminum Adjuvant (V710-002)

A Randomized, Multicenter, Double-Blind Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Single Dose of Merck 0657nI Staphylococcus Aureus Vaccine With Merck Aluminum Adjuvant or Without Merck Aluminum Adjuvant in Healthy Adults 18 to 70 Years of Age

The purpose of this study was to evaluate the safety, tolerability, and immunogenicity of the Merck 0657nI S. aureus vaccine (V710) either with or without Merck Aluminum Adjuvant (MAA).

Study Overview

• Status: Completed
• Conditions: Staphylococcal Infections
• Intervention / Treatment: Biological: V710 (30 µg) without MAA; Biological: V710 (30 µg) with MAA

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Participant was in good physical health
• Participant was able to understand study procedures and agreed to participate in the study by providing written informed consent.
• Participant was willing and able to participate in the entire study duration planned for up to 12 months (~360 days).
• Female participants of reproductive potential were required to have a negative urine pregnancy test immediately prior to study vaccination. Female participants of reproductive potential must have used an acceptable method of birth control for 2 weeks prior to enrollment, and agreed to use an acceptable method of birth control for 1 month after vaccination.

Exclusion criteria:

• Participant suffered from a chronic skin condition that predisposed the individual to the development of chronic skin or soft-tissue infections (e.g., psoriasis, chronic granulomatous disease, atopic dermatitis).
• Participant developed a serious infection (e.g., bacteremia, pneumonia, mediastinitis) attributed to S. aureus in the 12 months prior to screening.
• Participant had a history of anaphylaxis to aluminum-containing adjuvant or other vaccine components.
• Participant had a temperature of ≥100.4ºF (≥38.0ºC), oral equivalent, within 48 hours prior to receipt of V710.
• Participant had received a live virus vaccine within 30 days prior to receipt of V710 or was scheduled to receive vaccination with a live virus vaccine within 30 days following study entry.
• Participant had received any other licensed vaccine (including non-live virus vaccines) within 14 days prior to receipt of V710 or was scheduled to receive any other licensed vaccine (including non-live virus vaccines) within 30 days following study entry.
• Participant had received V710 in a prior clinical study (Merck V710 Protocol 001).
• Participant was administered immunoglobulin or blood product within 90 days prior to receipt of V710 or was scheduled to receive such products within 30 days following study entry.
• Participant had received treatment with systemic (intramuscular, oral, or intravenous) corticosteroids or another immunosuppressive medication (e.g., calcineurin inhibitors, mycophenolate, azathioprine) or biological agents (e.g., rituximab) in the 14 days prior to receipt of V710 or was anticipated to receive such medications for a chronic medical condition during the course of the study.
• Participant had a condition that required active medical intervention or monitoring to avert serious danger to the participant's health or well-being, such as diabetes mellitus, autoimmune disease, or clinically significant chronic medical conditions that were considered progressive, including but not limited to: coronary artery disease, congestive heart failure, cardiomyopathy, progressive valvular heart disease, chronic obstructive pulmonary disease, pulmonary fibrosis, active peptic ulcer disease, chronic renal disease, chronic hepatic disease, multiple sclerosis, progressive neuropathies, or seizure disorder requiring therapy in the past 3 years.
• Participant had known or suspected impairment of immunologic function including, but not limited to, the following conditions: autoimmune disease, diabetes mellitus, endstage renal disease, hepatic insufficiency/cirrhosis, splenectomy, or human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS).
• Participant had a condition in which repeated venipuncture or injections posed more than minimal risk for the subject, such as hemophilia, other severe coagulation disorders, or significantly impaired venous access.
• Participant was pregnant or breastfeeding, or planning to conceive within the 12-month study duration period.
• Participant had clinically significant abnormalities based on the participant or physical examination.
• Participant had recent history (within the past 5 years) or current evidence of drug or alcohol abuse.
• Participant had a major psychiatric illness, including any history of schizophrenia or severe psychosis, bipolar disorder requiring therapy, or any subject with suicidal ideation within the previous 3 years.
• Participant was legally or mentally incapacitated.
• Participant had participated in another clinical study in the past 4 weeks, or participant planned to participate in a treatment-based study or study in which an invasive procedure was to be performed during the first 3 months of this study (through Day 84).
• Participant had a history of any condition which, in the opinion of the investigator, posed an additional risk for the subject or confounded the results of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: V710 without MAA	Biological: V710 (30 µg) without MAA; Single 0.5-mL injection (30-µg) dose of V710 without MAA, intramuscularly
Active Comparator: V710 with MAA	Biological: V710 (30 µg) with MAA; Single 0.5-mL injection (30-µg) of V710 with MAA, intramuscularly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Positive Immune Response, Defined as a Change in Antibody Level Greater Than or Equal to a 2-fold-rise at Day 14 Compared to Baseline	Immunoglobulin G (IgG) antibodies were measured by a LUMINEX(TM) assay.	Baseline and Day 14 postvaccination
Geometric Mean Antibody Concentrations (GMC)	Immunoglobulin G (IgG) antibodies were measured by a LUMINEX(TM) assay.	Day 14 postvaccination
Change in Antibody Concentration (Titer) at Day 14 Compared to Baseline, Expressed as the Geometric Mean Fold-rise (GMFR)	Immunoglobulin G (IgG) antibodies were measured by a LUMINEX(TM) assay. The GMFR is the ratio of the antibody concentration at Day 14 to the antibody concentration at baseline.	Baseline and Day 14 postvaccination
Number of Vaccine-related Serious Adverse Experiences	Investigators were instructed to determine the seriousness and causality (relatedness to test vaccine) of each AE based on criteria defined in the protocol: A serious adverse event (SAE) is any AE that: results in death,; is life threatening,; results in a persistent or significant disability/incapacity,; results in or prolongs an existing inpatient hospitalization,; is a congenital anomaly/birth defect,; is a cancer,; is an overdose,; or is another important medical event that may require medical or surgical intervention to prevent one of the outcomes listed above.	Up to Day 360 postvaccination

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Harro CD, Betts RF, Hartzel JS, Onorato MT, Lipka J, Smugar SS, Kartsonis NA. The immunogenicity and safety of different formulations of a novel Staphylococcus aureus vaccine (V710): results of two Phase I studies. Vaccine. 2012 Feb 21;30(9):1729-36. doi: 10.1016/j.vaccine.2011.12.045. Epub 2011 Dec 20.

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): October 1, 2007

Study Registration Dates

• First Submitted: February 24, 2011
• First Submitted That Met QC Criteria: March 28, 2011
• First Posted (Estimate): March 29, 2011

Study Record Updates

• Last Update Posted (Estimate): April 10, 2015
• Last Update Submitted That Met QC Criteria: March 23, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Staphylococcus Aureus; Bacterial Vaccines; Adjuvanted Vaccine
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Staphylococcal Infections
• Other Study ID Numbers: V710-002