Pneumococcal Infection
Conditions
Brief summary
The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of V116 compared to PPSV23 in children and teenagers 2 through 17 years of age, who had completed routine pneumococcal vaccine as infants/toddlers. Researchers want to learn if V116 is as good as, or is better than the PPSV23 vaccine in terms of the antibody immune response. V116 and PPSV23 will be studied in children and teenagers who have a higher risk of getting pneumococcal disease (PD).
Interventions
BIOLOGICALV116
Pneumococcal 21-valent conjugate vaccine with 4 μg of each of the following pneumococcal polysaccharides (PnPs) antigen: 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, and 35B in each 0.5 mL sterile solution
BIOLOGICALPPSV23
Pneumococcal 23-valent conjugate vaccine with 25 μg of each of the following PnPs antigen: 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F in each 0.5 mL sterile solution
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Has a diagnosis and stable medical management (for at least 3 months) of one of the following risk conditions for pneumococcal disease: Diabetes mellitus, chronic compensated liver disease, chronic lung disease, chronic heart disease, or chronic kidney disease. * Has completed pneumococcal conjugate vaccine regimen (PCV7, PCV10, or PCV13) at least 8 weeks before study enrollment.
Exclusion criteria
* Had a curative procedure/surgery for chronic heart disease and does not require medication, follow-up, additional interventions, or further management per local guidelines. * Has a history of active hepatitis within 3 months before study vaccination. * Has a history of diabetic ketoacidosis or 2 or more episodes of severe, symptomatic hypoglycemia within 3 months before study vaccination. * Has a history of severely decreased kidney function dialysis, autoimmune related chronic kidney disease, nephrotic syndrome of any cause, or an acute/reversible cause of kidney disease. * Has a history of severe pulmonary hypertension or history of Eisenmenger syndrome. * History of invasive pneumococcal disease within 3 years before study vaccination.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Solicited Injection-site Adverse Events (AEs) | Up to 5 days postvaccination | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited injection-site AEs included pain/tenderness, redness/erythema, and swelling. |
| Percentage of Participants With Solicited Systemic AEs | Up to 5 days post vaccination | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited systemic AEs included muscle aches all over the body (myalgia), headache, tiredness (fatigue), hives or welts (urticaria), irritability, joint pain (arthralgia), drowsiness (somnolence), feeling sick (malaise), and fever (pyrexia). |
| Percentage of Participants With Vaccine-related Serious Adverse Events (SAEs) | Up to approximately 6 months | A vaccine-related SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is another important medical event. |
| Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity (OPA) Responses | 30 days postvaccination | Opsonophagocytic activity (OPA) for the serotypes in V116 will be determined using a multiplexed opsonophagocytic assay (MOPA). Serotype-specific OPA GMTs and GMT ratios with 95% confidence intervals (CIs) were calculated using a constrained longitudinal data analysis (cLDA) model. The 12 common pneumococcal serotypes in both V116 and PPSV23 were as follows: 3, 7F, 8, 9N, 10A, 11A, 12F, 17F, 19A, 20A, 22F, and 33F. The 9 unique pneumococcal serotypes in V116 were as follows: 6A, 15A, 15C, 16F, 23A, 23B, 24F, 31, and 35B. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Concentrations (GMCs) of Serotype-specific Immunoglobulin G (IgG) After Vaccination | 30 days postvaccination | The GMCs for serotype-specific IgG antibodies will be determined using pneumococcal electrochemiluminescence (PnECL). Serotype-specific IgGs and GMC ratios with 95% CIs were calculated using a cLDA model. The 12 common pneumococcal serotypes in both V116 and PPSV23 were as follows: 3, 7F, 8, 9N, 10A, 11A, 12F, 17F, 19A, 20A, 22F, and 33F. The 9 unique pneumococcal serotypes in V116 were as follows: 6A, 15A, 15C, 16F, 23A, 23B, 24F, 31, and 35B. |
| Geometric Mean Fold Rise (GMFR) From Baseline in Serotype-specific OPA GMTs | Baseline (Day 1) and 30 days postvaccination | The GMFR from baseline in serotype-specific OPA GMTs was determined using MOPA at baseline and 30 days postvaccination and derived from a cLDA model. The GMFR (Day 30 GMT/Day 1 GMT) from baseline (Day 1) to Day 30 of each pneumococcal OPA serotype was calculated. The 12 common pneumococcal serotypes in both V116 and PPSV23 were as follows: 3, 7F, 8, 9N, 10A, 11A, 12F, 17F, 19A, 20A, 22F, and 33F. The 9 unique pneumococcal serotypes in V116 were as follows: 6A, 15A, 15C, 16F, 23A, 23B, 24F, 31, and 35B. |
| Percentage of Participants With ≥4-fold Rise From Baseline in Serotype-specific OPAs GMTs | Baseline (Day 1) and Day 30 postvaccination | The percentage of participants with ≥4-fold rise from baseline (Day 1) to Day 30 in GMTs of each pneumococcal serotype was calculated. Titer levels were determined by the MOPA and derived from a cLDA model. The 12 common pneumococcal serotypes in both V116 and PPSV23 were as follows: 3, 7F, 8, 9N, 10A, 11A, 12F, 17F, 19A, 20A, 22F, and 33F. The 9 unique pneumococcal serotypes in V116 were as follows: 6A, 15A, 15C, 16F, 23A, 23B, 24F, 31, and 35B. |
| GMFR From Baseline in Serotype-specific IgG GMCs | Baseline (Day 1) and Day 30 postvaccination | The GMFR from baseline in serotype-specific IgG GMCs was determined using PnECL at baseline and 30 days postvaccination and derived from a cLDA model. The GMFR (Day 30 GMT/Day 1 GMT) from baseline (Day 1) to Day 30 of each pneumococcal IgG serotype was calculated. The 12 common pneumococcal serotypes in both V116 and PPSV23 were as follows: 3, 7F, 8, 9N, 10A, 11A, 12F, 17F, 19A, 20A, 22F, and 33F. |
| Percentage of Participants With ≥4-fold Rise From Baseline in Serotype-specific IgG GMCs | Baseline (Day 1) and Day 30 postvaccination | The percentage of participants with ≥4-fold rise from baseline (Day 1) to Day 30 in GMCs of each pneumococcal serotype was calculated. Titer levels were determined by PnECL and derived from a cLDA model. The 12 common pneumococcal serotypes in both V116 and PPSV23 were as follows: 3, 7F, 8, 9N, 10A, 11A, 12F, 17F, 19A, 20A, 22F, and 33F. The 9 unique pneumococcal serotypes in V116 were as follows: 6A, 15A, 15C, 16F, 23A, 23B, 24F, 31, and 35B. |
Countries
Canada, Chile, Colombia, Finland, France, Israel, Japan, Poland, Spain, Sweden, Thailand, Turkey (Türkiye), United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Pre-assignment details
Children and adolescents between 2 and 18 years of age with an increased risk of pneumococcal disease were enrolled in this study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 7.8 Years STANDARD_DEVIATION 3.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 158 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 298 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 91 Participants |
| Race (NIH/OMB) Asian | 85 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants |
| Race (NIH/OMB) More than one race | 48 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 | 525 Participants |
| Sex: Female, Male Female | 362 Participants |
| Sex: Female, Male Male | 311 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 531 | 2 / 351 |
| other Total, other adverse events | 408 / 527 | 237 / 347 |
| serious Total, serious adverse events | 29 / 527 | 25 / 347 |
Outcome results
None listed