Pneumococcal Disease
Conditions
Brief summary
The primary purpose of this phase 3, single-arm, open-label study is to evaluate the safety and immunogenicity of a 4-dose regimen of V114 administered to healthy infants in South Korea.
Interventions
BIOLOGICALV114
15-valent pneumococcal conjugate vaccine (PCV) containing 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) present in Prevnar 13™ plus 2 additional serotypes (22F, 33F) in each 0.5 mL sterile suspension for intramuscular injection.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
42 Days to 90 Days
Healthy volunteers
Yes
Inclusion criteria
* is a healthy South Korean male or female who is 42 to 90 days of age at the time of signing informed consent * has a parent or legally acceptable representative who understands study procedures, alternative treatments available, and risks involved and voluntarily agrees to participate by signing informed consent
Exclusion criteria
* has a history of invasive pneumococcal disease or known history of other culture positive pneumococcal disease * has known hypersensitivity to pneumococcal conjugate vaccine, any licensed pediatric vaccine to be administered concomitantly, or any diphtheria toxoid-containing vaccine * has had a recent febrile illness (rectal temperature ≥38.1°C \[≥100.5°F\] or axillary temperature ≥37.8°C \[≥100.0°F\]) within 72 hours prior to receipt of study vaccine * has known or suspected impairment of immunological function * has or his/her mother has human immunodeficiency virus (HIV) infection * has or his/her mother has hepatitis B surface antigen-positive test * has known or history of functional or anatomic asplenia * has a history of autoimmune disease * has a history or suspected history of neurological disorder * has received a pneumococcal vaccine prior to study entry * has received, or is anticipated to need, corticosteroid therapy * has received a blood transfusion of immunoglobulin products * has participated in another clinical study of an investigational product
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With ≥1 Vaccine-related Serious Adverse Events | Up to approximately 14.5 months | A serious adverse event (SAE) is an AE that is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. The percentage of participants with a vaccine-related SAE following any dose of V114 was reported. Vaccine-related SAEs were counted starting after vaccine dose 1 through completion of study. |
| Percentage of Participants With ≥1 Solicited Injection-site Adverse Events | Up to 7 days after any vaccination, up to a total of ~ 13 months | An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following any of the doses of V114, the percentage of participants with solicited injection-site AEs was assessed. The solicited injection-site AEs consist of erythema, induration, pain, and swelling. |
| Percentage of Participants With ≥1 Solicited Systemic Adverse Events | Up to 7 days after any vaccination, up to a total of ~ 13 months | An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following any of the doses of V114, the percentage of participants with solicited systemic AEs was assessed. The solicited systemic AEs consist of decreased appetite, irritability, somnolence, and urticaria. |
| Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 3 | 30 days after vaccination 3 (Up to a total of ~5 months) | The anti-pneumococcal polysaccharides (PnPs) serotype-specific IgG geometric mean concentrations (GMCs) at 30 days postdose 3 for each serotype-specific were reported. The multiplex, electrochemiluminescence (ECL)-based PnECL v2.0 assay was used to quantify IgG serotype-specific antibodies. |
| Percentage of Participants Discontinuing Study Therapy Due to an Adverse Event | Up to approximately 13 months | An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who discontinued study treatment due to an AE is reported. |
| Percentage of Participants With Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G ≥0.35 µg/mL | 30 days after vaccination 3 (Up to a total of ~5 months) | The percentage of participants with immunoglobulin G (IgG) threshold values of ≥0.35 µg/mL for the 15 serotypes contained in V114 (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F) at 30 days postdose 3 is reported. The multiplex, pneumococcal electrochemiluminescence (PnECL) v2.0 assay was used to quantify IgG serotype-specific antibodies. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 4 | 30 days after vaccination 4 (Up to a total of ~14 months) | The anti-PnPs serotype-specific IgG GMCs at 30 days postdose 4 for each serotype-specific were reported. The multiplex, ECL-based PnECL v2.0 assay was used. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| V114 Participants received 4 total doses of V114, administered at approximately 2, 4, 6, and 12 to 15 months of age. | 58 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Randomized by mistake without study treatment | 1 |
| Overall Study | Withdrawal by parent/guardian | 4 |
Baseline characteristics
| Characteristic | V114 |
|---|---|
| Age, Continuous | 8.7 weeks STANDARD_DEVIATION 1.2 |
| Age, Customized 85 years and over | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 0 Participants |
| Age, Customized Adults (18-64 years) | 0 Participants |
| Age, Customized Children (2-11 years) | 0 Participants |
| Age, Customized From 65-84 years | 0 Participants |
| Age, Customized Infants and toddlers (28 days-23 months) | 58 Participants |
| Age, Customized In utero | 0 Participants |
| Age, Customized Newborns (0-27 days) | 0 Participants |
| Age, Customized Preterm newborn infants (gestational age < 37 wks) | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 58 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 33 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 58 |
| other Total, other adverse events | 56 / 57 |
| serious Total, serious adverse events | 4 / 57 |
Outcome results
Primary
Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 3
The anti-pneumococcal polysaccharides (PnPs) serotype-specific IgG geometric mean concentrations (GMCs) at 30 days postdose 3 for each serotype-specific were reported. The multiplex, electrochemiluminescence (ECL)-based PnECL v2.0 assay was used to quantify IgG serotype-specific antibodies.
Time frame: 30 days after vaccination 3 (Up to a total of ~5 months)
Population: All randomized participants without protocol deviations that could have substantially impacted the results of the immunogenicity endpoint and who had sufficient data to perform the analyses were analyzed. Deviations include randomized but not vaccinated, prior pneumococcal vaccine, vaccination out of window, blood draw out of window, prohibited concomitant medication or vaccine, or missing serology results.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 3 | Serotype 6A | 2.16 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 3 | Serotype 6B | 2.53 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 3 | Serotype 1 | 1.69 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 3 | Serotype 3 | 1.70 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 3 | Serotype 4 | 1.87 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 3 | Serotype 5 | 2.14 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 3 | Serotype 7F | 2.80 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 3 | Serotype 9V | 2.01 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 3 | Serotype 14 | 7.47 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 3 | Serotype 18C | 1.90 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 3 | Serotype 19A | 2.20 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 3 | Serotype 19F | 3.04 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 3 | Serotype 22F | 5.97 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 3 | Serotype 23F | 1.71 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 3 | Serotype 33F | 2.41 μg/mL |
Primary
Percentage of Participants Discontinuing Study Therapy Due to an Adverse Event
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who discontinued study treatment due to an AE is reported.
Time frame: Up to approximately 13 months
Population: The analysis population consisted of all participants who received at least 1 dose of study vaccination.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| V114 | Percentage of Participants Discontinuing Study Therapy Due to an Adverse Event | 0.0 Percentage of Participants | 95% Confidence Interval 0 |
Primary
Percentage of Participants With ≥1 Solicited Injection-site Adverse Events
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following any of the doses of V114, the percentage of participants with solicited injection-site AEs was assessed. The solicited injection-site AEs consist of erythema, induration, pain, and swelling.
Time frame: Up to 7 days after any vaccination, up to a total of ~ 13 months
Population: All randomized participants who received at least 1 dose of study vaccination were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| V114 | Percentage of Participants With ≥1 Solicited Injection-site Adverse Events | Injection site erythema | 54.4 Percentage of Participants |
| V114 | Percentage of Participants With ≥1 Solicited Injection-site Adverse Events | Injection site induration | 57.9 Percentage of Participants |
| V114 | Percentage of Participants With ≥1 Solicited Injection-site Adverse Events | Injection site pain | 50.9 Percentage of Participants |
| V114 | Percentage of Participants With ≥1 Solicited Injection-site Adverse Events | Injection site swelling | 59.6 Percentage of Participants |
Primary
Percentage of Participants With ≥1 Solicited Systemic Adverse Events
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following any of the doses of V114, the percentage of participants with solicited systemic AEs was assessed. The solicited systemic AEs consist of decreased appetite, irritability, somnolence, and urticaria.
Time frame: Up to 7 days after any vaccination, up to a total of ~ 13 months
Population: All randomized participants who received at least 1 dose of study vaccination were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| V114 | Percentage of Participants With ≥1 Solicited Systemic Adverse Events | Decreased appetite | 71.9 Percentage of Participants |
| V114 | Percentage of Participants With ≥1 Solicited Systemic Adverse Events | Irritability | 89.5 Percentage of Participants |
| V114 | Percentage of Participants With ≥1 Solicited Systemic Adverse Events | Somnolence | 82.5 Percentage of Participants |
| V114 | Percentage of Participants With ≥1 Solicited Systemic Adverse Events | Urticaria | 8.8 Percentage of Participants |
Primary
Percentage of Participants With ≥1 Vaccine-related Serious Adverse Events
A serious adverse event (SAE) is an AE that is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. The percentage of participants with a vaccine-related SAE following any dose of V114 was reported. Vaccine-related SAEs were counted starting after vaccine dose 1 through completion of study.
Time frame: Up to approximately 14.5 months
Population: All randomized participants who received at least 1 dose of study vaccination were analyzed.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| V114 | Percentage of Participants With ≥1 Vaccine-related Serious Adverse Events | 0.0 Percentage of Participants | 95% Confidence Interval 0 |
Primary
Percentage of Participants With Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G ≥0.35 µg/mL
The percentage of participants with immunoglobulin G (IgG) threshold values of ≥0.35 µg/mL for the 15 serotypes contained in V114 (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F) at 30 days postdose 3 is reported. The multiplex, pneumococcal electrochemiluminescence (PnECL) v2.0 assay was used to quantify IgG serotype-specific antibodies.
Time frame: 30 days after vaccination 3 (Up to a total of ~5 months)
Population: All randomized participants without protocol deviations that could have substantially impacted the results of the immunogenicity endpoint and who had sufficient data to perform the analyses were analyzed. Deviations include randomized but not vaccinated, prior pneumococcal vaccine, vaccination out of window, blood draw out of window, prohibited concomitant medication or vaccine, or missing serology results.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| V114 | Percentage of Participants With Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G ≥0.35 µg/mL | Serotype 9V | 100.0 Percentage of Participants |
| V114 | Percentage of Participants With Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G ≥0.35 µg/mL | Serotype 14 | 100.0 Percentage of Participants |
| V114 | Percentage of Participants With Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G ≥0.35 µg/mL | Serotype 1 | 100.0 Percentage of Participants |
| V114 | Percentage of Participants With Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G ≥0.35 µg/mL | Serotype 3 | 100.0 Percentage of Participants |
| V114 | Percentage of Participants With Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G ≥0.35 µg/mL | Serotype 4 | 100.0 Percentage of Participants |
| V114 | Percentage of Participants With Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G ≥0.35 µg/mL | Serotype 5 | 100.0 Percentage of Participants |
| V114 | Percentage of Participants With Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G ≥0.35 µg/mL | Serotype 6A | 100.0 Percentage of Participants |
| V114 | Percentage of Participants With Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G ≥0.35 µg/mL | Serotype 6B | 95.7 Percentage of Participants |
| V114 | Percentage of Participants With Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G ≥0.35 µg/mL | Serotype 7F | 100.0 Percentage of Participants |
| V114 | Percentage of Participants With Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G ≥0.35 µg/mL | Serotype 18C | 97.9 Percentage of Participants |
| V114 | Percentage of Participants With Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G ≥0.35 µg/mL | Serotype 19A | 97.9 Percentage of Participants |
| V114 | Percentage of Participants With Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G ≥0.35 µg/mL | Serotype 19F | 100.0 Percentage of Participants |
| V114 | Percentage of Participants With Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G ≥0.35 µg/mL | Serotype 22F | 100.0 Percentage of Participants |
| V114 | Percentage of Participants With Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G ≥0.35 µg/mL | Serotype 23F | 100.0 Percentage of Participants |
| V114 | Percentage of Participants With Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G ≥0.35 µg/mL | Serotype 33F | 97.9 Percentage of Participants |
Secondary
Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 4
The anti-PnPs serotype-specific IgG GMCs at 30 days postdose 4 for each serotype-specific were reported. The multiplex, ECL-based PnECL v2.0 assay was used.
Time frame: 30 days after vaccination 4 (Up to a total of ~14 months)
Population: All randomized participants without protocol deviations that could have substantially impacted the results of the immunogenicity endpoint and who had sufficient data to perform the analyses were analyzed. Deviations include vaccination out of window, blood draw out of window, or prohibited concomitant medication or vaccine.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 4 | Serotype 1 | 2.24 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 4 | Serotype 3 | 1.32 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 4 | Serotype 4 | 1.86 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 4 | Serotype 5 | 3.27 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 4 | Serotype 6A | 5.77 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 4 | Serotype 6B | 6.80 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 4 | Serotype 7F | 5.17 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 4 | Serotype 9V | 3.27 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 4 | Serotype 14 | 9.04 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 4 | Serotype 18C | 3.81 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 4 | Serotype 19A | 4.91 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 4 | Serotype 19F | 5.41 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 4 | Serotype 22F | 9.20 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 4 | Serotype 23F | 2.82 μg/mL |
| V114 | Geometric Mean Concentrations of Anti-Pneumococcal Polysaccharides Serotype-specific Immunoglobulin G at 30 Days Postdose 4 | Serotype 33F | 6.21 μg/mL |