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)

A Phase 3, Multicenter, Randomized, Double-blind, Active Comparator-controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 Followed by Administration of PNEUMOVAX™23 Six Months Later in Immunocompetent Adults Between 18 and 49 Years of Age at Increased Risk for Pneumococcal Disease (PNEU - DAY)

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.

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:

  1. Diabetes mellitus Type 1 or Type 2 and with hemoglobin A1c (HgA1c) <10%
  2. Chronic liver disease with documented history of compensated cirrhosis (Child-Pugh Score A)
  3. Confirmed diagnosis of Chronic Obstructive Pulmonary Disease (COPD) with spirometric Global Initiative for Chronic Obstructive Lung Disease Stage 1 to 3
  4. Confirmed diagnosis of mild or moderate persistent asthma receiving guideline directed therapy
  5. Confirmed diagnosis of chronic heart disease (New York Heart Association [NYHA] heart failure Class 1 to 3, receiving guideline-directed oral heart failure treatment) due to reduced or preserved ejection fraction or due to non-cyanotic congenital heart disease.
  6. Current smoker

• Female participant: not pregnant, not breastfeeding and 1) not of childbearing potential, or 2) of childbearing potential and agrees to practice contraception through 6 weeks after last administration of study vaccine.

Exclusion Criteria:

• History of active hepatitis within the prior 3 months
• History of diabetic ketoacidosis, or >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.