Phase 3
N=1,515
A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 Followed by PNEUMOVAX™23 in Adults at Increased Risk for Pneumococcal Disease (V114-017/PNEU-DAY)
Pneumococcal Infections
Bottom Line
View on ClinicalTrials.gov: NCT03547167 ↗Enrolled (actual)
1,515
Serious AEs
2.3%
Results posted
Jan 2021
Primary outcome: Primary: Percentage of Participants With Solicited Injection-site Adverse Events Following V114 or Prevnar 13™ — 15.1; 14.0; 75.8; 68.8 Percentage of Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- V114 (Biological); Prevnar 13™ (Biological); PNEUMOVAX™23 (Biological)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- Jan 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Solicited Injection-site Adverse Events Following V114 or Prevnar 13™ |
15.1; 14.0; 75.8; 68.8; 21.7; 22.2 | — |
| PRIMARY Percentage of Participants With Solicited Systemic Adverse Events Following V114 or Prevnar 13™ |
12.7; 11.6; 34.3; 36.8; 26.5; 24.9 | — |
| PRIMARY Percentage of Participants With a Vaccine-related Serious Adverse Event Following V114 or Prevnar 13™ |
0.0; 0.0 | — |
| PRIMARY Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity Day 30 Following V114 or Prevnar 13™ |
268.6; 267.2; 199.3; 150.6; 1416.0; 2576.1 | — |
| SECONDARY Percentage of Participants With Solicited Injection-site Adverse Events Following PNEUMOVAX™23 |
22.6; 25.5; 68.8; 67.0; 29.4; 32.2 | — |
| SECONDARY Percentage of Participants With Solicited Systemic Adverse Events Following PNEUMOVAX™23 |
12.0; 11.0; 30.1; 30.7; 21.2; 21.2 | — |
| SECONDARY Percentage of Participants With a Vaccine-related Serious Adverse Event Following PNEUMOVAX™23 |
0.0; 0.3 | — |
| SECONDARY Geometric Mean Concentration of Serotype-specific Immunoglobulin G at Day 30 |
3.56; 4.59; 0.77; 0.63; 1.53; 2.71 | — |
| SECONDARY Geometric Mean Fold Rise in Serotype-specific OPA Day 1 to Day 30 |
22.8; 21.9; 5.8; 4.8; 17.9; 33.4 | — |
| SECONDARY GMFR in Serotype-specific IgG Day 1 to Day 30 |
12.2; 15.7; 4.1; 3.6; 8.0; 16.2 | — |
| SECONDARY Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Day 1 to Day 30 |
83.9; 81.4; 62.2; 56.8; 79.0; 87.8 | — |
| SECONDARY Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Day 1 to Day 30 |
81.2; 86.4; 44.8; 41.1; 70.1; 86.1 | — |
| SECONDARY Geometric Mean Titer of Serotype-specific OPA at Month 7 |
266.6; 214.4; 211.0; 208.0; 1734.5; 1980.6 | — |
| SECONDARY Geometric Mean Concentration of Serotype-specific IgG at Month 7 |
2.91; 3.42; 0.66; 0.68; 1.33; 1.77 | — |
| SECONDARY GMFR in Serotype-specific OPA Day 1 to Month 7 |
22.6; 17.4; 6.1; 6.4; 21.6; 25.6 | — |
| SECONDARY GMFR in Serotype-specific IgG Day 1 to Month 7 |
10.1; 11.4; 3.5; 3.8; 7.1; 10.7 | — |
| SECONDARY Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Day 1 to Month 7 |
87.7; 83.7; 66.5; 66.7; 84.3; 86.4 | — |
| SECONDARY Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Day 1 to Month 7 |
81.4; 83.6; 40.7; 46.1; 71.2; 82.0 | — |
| SECONDARY GMFR in Serotype-specific OPA Month 6 to Month 7 |
3.2; 2.0; 2.0; 2.4; 2.7; 1.7 | — |
| SECONDARY GMFR in Serotype-specific IgG Month 6 to Month 7 |
2.1; 1.5; 1.7; 2.0; 2.0; 1.6 | — |
| SECONDARY Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Month 6 to Month 7 |
40.2; 21.4; 19.2; 25.5; 30.8; 14.9 | — |
| SECONDARY Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Month 6 to Month 7 |
16.4; 8.2; 6.3; 13.8; 15.2; 7.5 | — |
Summary
This study is designed to 1) describe the safety, tolerability, and immunogenicity of V114 and Prevnar 13™ in pneumococcal vaccine-naïve adults at increased risk for pneumococcal disease and to 2) describe the safety, tolerability, and immunogenicity of PNEUMOVAX™23 when administered 6 months after receipt of either V114 or Prevnar 13™. Increased risk for pneumococcal disease is defined as 1) an underlying medical condition, 2) behavioral habits such as smoking or alcohol use, or 3) living in a community/environment with increased risk of disease transmission.
Eligibility Criteria
Inclusion Criteria
- Native American participant enrolled from any of the clinical sites of the Johns Hopkins Center for American Indian Health (CAIH) without any of the pre-specified risk conditions for pneumococcal disease listed below, OR Native American participant enrolled from any of the CAIH sites or participant from a site other than CAIH with ≥1 of the following risk conditions for pneumococcal disease:
- Diabetes mellitus Type 1 or Type 2 and with hemoglobin A1c (HgA1c) 1 episodes of severe, symptomatic hypoglycemia within the prior 3 months
- Myocardial infarction, acute coronary syndrome, transient ischemic attack, and ischemic or hemorrhagic stroke within the prior 3 months
- History of severe pulmonary hypertension or history of Eisenmenger syndrome
- History of invasive pneumococcal disease (IPD) or known history of other culture-positive pneumococcal disease within the prior 3 years
- Known hypersensitivity to any vaccine component, pneumococcal conjugate vaccine, or diphtheria toxoid-containing vaccine
- Known or suspected impairment of immunological function (including human immunodeficiency virus (HIV) infection or autoimmune disease)
- History of malignancy within the prior 5 years, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
- History of Stage 4 or 5 Chronic Kidney Disease or nephrotic syndrome
- History of alcohol withdrawal or alcohol withdrawal seizure within the prior 12 months
- History of coagulation disorder contraindicating intramuscular vaccination
- History of hospitalization within the prior 3 months
- Planned organ transplantation (heart, liver, lung, kidney, or pancreas) or other planned major surgery during the duration of this study.
- Expected survival for less than 1 year according to the investigator's judgment.
- Female participant: positive urine or serum pregnancy test
- Prior administration of any pneumococcal vaccine
- Received systemic corticosteroids (prednisone equivalent of ≥20 mg/day) for ≥14 consecutive days and has not completed within the prior 30 days
- Received systemic corticosteroids exceeding physiologic replacement doses within 14 days before study vaccination
- Receiving immunosuppressive or immunomodulatory therapy with a biological agent
- Received any licensed, non-live vaccine within 14 days before receipt of study vaccine or is scheduled to receive any licensed, non-live vaccine within 30 days following receipt of study vaccine
- Received any live vaccine within 30 days before receipt of any study vaccine or is scheduled to receive any live vaccine within 30 days following receipt of any study vaccine
- Received a blood transfusion or blood products within the prior 6 months
- Receiving chronic home oxygen therapy
- Participated in another clinical study of an investigational product within the prior 2 months
- Current user of recreational or illicit drugs or history of drug abuse or dependence
- Diabetes mellitus with HgA1c ≥10%
- Chronic liver disease with Child-Pugh Class B or C cirrhosis
- Chronic lung disease with Chronic Obstructive Pulmonary Disease (COPD) GOLD Stage 4 or severe persistent asthma
- Chronic heart disease with NYHA heart failure Class 4.
Data sourced from ClinicalTrials.gov (NCT03547167). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.