Staphylococcal Infections
Conditions
Keywords
Bacterial Vaccines, Staphylococcus Aureus, Adjuvanted Vaccine
Brief summary
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).
Interventions
BIOLOGICALV710 (30 µg) with MAA
Single 0.5-mL injection (30-µg) of V710 with MAA, intramuscularly
BIOLOGICALV710 (30 µg) without MAA
Single 0.5-mL injection (30-µg) dose of V710 without MAA, intramuscularly
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline and Day 14 postvaccination | Immunoglobulin G (IgG) antibodies were measured by a LUMINEX(TM) assay. |
| Geometric Mean Antibody Concentrations (GMC) | Day 14 postvaccination | Immunoglobulin G (IgG) antibodies were measured by a LUMINEX(TM) assay. |
| Change in Antibody Concentration (Titer) at Day 14 Compared to Baseline, Expressed as the Geometric Mean Fold-rise (GMFR) | Baseline and Day 14 postvaccination | 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. |
| Number of Vaccine-related Serious Adverse Experiences | Up to Day 360 postvaccination | 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| V710 With MAA Single 0.5-mL injection (30-µg) dose of V710 with MAA, intramuscularly. | 32 |
| V710 Without MAA Single 0.5-mL injection (30-µg) dose of V710 without MAA, intramuscularly. | 32 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Subject moved | 0 | 1 |
Baseline characteristics
| Characteristic | V710 With MAA | V710 Without MAA | Total |
|---|---|---|---|
| Age, Customized 17 and under | 0 participants | 0 participants | 0 participants |
| Age, Customized 18 to 29 | 6 participants | 5 participants | 11 participants |
| Age, Customized 30 to 39 | 1 participants | 4 participants | 5 participants |
| Age, Customized 40 to 49 | 9 participants | 7 participants | 16 participants |
| Age, Customized 50 to 59 | 12 participants | 10 participants | 22 participants |
| Age, Customized 60 to 69 | 4 participants | 6 participants | 10 participants |
| Age, Customized Over 69 | 0 participants | 0 participants | 0 participants |
| Sex: Female, Male Female | 20 Participants | 13 Participants | 33 Participants |
| Sex: Female, Male Male | 12 Participants | 19 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 32 | 17 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 32 |
Outcome results
Primary
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.
Time frame: Baseline and Day 14 postvaccination
Population: The per-protocol analysis excluded patients who had missing baseline and/or postvaccination (Day 14) serology data and patients who developed a S. aureus infection during the 14 days postvaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| V710 With MAA | Change in Antibody Concentration (Titer) at Day 14 Compared to Baseline, Expressed as the Geometric Mean Fold-rise (GMFR) | 4.5 ratio of IgG titer at Day 14 to baseline |
| V710 Without MAA | Change in Antibody Concentration (Titer) at Day 14 Compared to Baseline, Expressed as the Geometric Mean Fold-rise (GMFR) | 4.0 ratio of IgG titer at Day 14 to baseline |
Primary
Geometric Mean Antibody Concentrations (GMC)
Immunoglobulin G (IgG) antibodies were measured by a LUMINEX(TM) assay.
Time frame: Day 14 postvaccination
Population: The per-protocol analysis excluded patients who had missing baseline and/or postvaccination (Day 14) serology data and patients who developed a S. aureus infection during the 14 days postvaccination.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| V710 With MAA | Geometric Mean Antibody Concentrations (GMC) | 115.4 mcg/mL |
| V710 Without MAA | Geometric Mean Antibody Concentrations (GMC) | 99.1 mcg/mL |
Primary
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.
Time frame: Baseline and Day 14 postvaccination
Population: The per-protocol analysis excluded patients who had missing baseline and/or postvaccination (Day 14) serology data and patients who developed a S. aureus infection during the 14 days postvaccination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| V710 With MAA | 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 | 27 participants |
| V710 Without MAA | 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 | 23 participants |
Primary
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.
Time frame: Up to Day 360 postvaccination
Population: Any subject who received clinical material and had at least 1 day of safety follow-up was included in the safety summary.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| V710 With MAA | Number of Vaccine-related Serious Adverse Experiences | 0 participants |
| V710 Without MAA | Number of Vaccine-related Serious Adverse Experiences | 0 participants |