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)

Merck Sharp & Dohme LLC1,515 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

1,515

Conditions

Pneumococcal Infections

Interventions

V114

15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F (2 mcg each), serotype 6B (4 mcg) and Merck Aluminum Phosphate Adjuvant (125 mcg) in each 0.5 mL dose

Prevnar 13™BIOLOGICAL

13-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 mcg) and 6B (4.4 mcg), and aluminum phosphate adjuvant (125 mcg aluminum) in each 0.5 ml dose

PNEUMOVAX™23BIOLOGICAL

23-valent pneumococcal polysaccharide vaccine with serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F (25 mcg each) in each 0.5 mL dose

Eligibility

Sex: ALLMin age: 18 YearsMax age: 49 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (78)

Chinle Comprehensive Health Care Facility ( Site 0001)

Chinle, Arizona, United States

Fort Defiance Center for American Indian Health ( Site 0002)

Fort Defiance, Arizona, United States

Pulmonary Associates, PA ( Site 0043)

Glendale, Arizona, United States

Central Phoenix Medical Clinic, LLC ( Site 0031)

Phoenix, Arizona, United States

Whiteriver Center for American Indian Health ( Site 0005)

Whiteriver, Arizona, United States

Outcomes

Primary Outcomes

Percentage of Participants With Solicited Injection-site Adverse Events Following V114 or Prevnar 13™

An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Following Vaccination 1 with either V114 or Prevnar 13™, the percentage of participants with solicited injection-site AEs was assessed. The solicited injection-site AEs assessed were redness/erythema, swelling, and tenderness/pain. Estimated confidence intervals (CIs) are calculated based on the exact binomial method proposed by Clopper and Pearson.

Time frame: Up to 5 days after Vaccination 1

Percentage of Participants With Solicited Systemic Adverse Events Following V114 or Prevnar 13™

An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Following vaccination with V114 or Prevnar 13™, the percentage of participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed were muscle pain/myalgia, joint pain/arthralgia, headache, and tiredness/fatigue. Estimated CIs are calculated based on the exact binomial method proposed by Clopper and Pearson.

Time frame: Up to 14 days after Vaccination 1

Percentage of Participants With a Vaccine-related Serious Adverse Event Following V114 or Prevnar 13™

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. Relatedness of an SAE to the study vaccine was determined by the investigator. Following vaccination with V114 or Prevnar 13™, the percentage of serious adverse events of V114 compared with Prevnar 13™ was assessed. Estimated CIs are calculated based on the exact binomial method proposed by Clopper and Pearson.

Time frame: Up to Month 6 (before Vaccination 2)

Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity Day 30 Following V114 or Prevnar 13™

The geometric mean titer (GMT) of serotype-specific opsonophagocytic activity (OPA) for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using a multiplex opsonophagocytic assay. The within-group 95% CIs are obtained by exponentiating the CIs of the mean of the natural log values based on the t-distribution.

Time frame: Day 30

Secondary Outcomes

Percentage of Participants With Solicited Injection-site Adverse Events Following PNEUMOVAX™23

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 Vaccination 2 with PNEUMOVAX™23, the percentage of participants with solicited injection-site AEs was assessed. The solicited injection-site AEs assessed were redness/erythema, swelling, and tenderness/pain. Estimated CIs are calculated based on the exact binomial method proposed by Clopper and Pearson and are provided in accordance with the statistical analysis plan.

Time frame: Up to 5 days after Vaccination 2 (Month 6)

Percentage of Participants With Solicited Systemic Adverse Events Following PNEUMOVAX™23

An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Following Vaccination 2 with PNEUMOVAX™23, the percentage of participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed were muscle pain/myalgia, joint pain/arthralgia, headache, and tiredness/fatigue. Estimated CIs are calculated based on the exact binomial method proposed by Clopper and Pearson.

Time frame: Up to 14 days after Vaccination 2 (Month 6)

Percentage of Participants With a Vaccine-related Serious Adverse Event Following PNEUMOVAX™23

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. Relatedness of an SAE to the study vaccine was determined by the investigator. Following vaccination with PNEUMOVAX™23, the percentage of serious adverse events of V114 compared with Prevnar 13™ was assessed. Estimated CIs are calculated based on the exact binomial method proposed by Clopper and Pearson.

Time frame: From Month 6 (before Vaccination 2) to Month 7

Geometric Mean Concentration of Serotype-specific Immunoglobulin G at Day 30

The geometric mean concentration (GMC) of serotype-specific immunoglobulin G (IgG) for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using an electrochemiluminescence assay. The within-group 95% CIs are obtained by exponentiating the CIs of the mean of the natural log values based on the t-distribution.

Data from ClinicalTrials.gov

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Inland Empire Clinical Trials, LLC ( Site 0052)

Rialto, California, United States

Top Medical Research, Inc ( Site 0033)

Cutler Bay, Florida, United States

Indago Research & Health Center, Inc ( Site 0054)

Hialeah, Florida, United States

Renstar Medical Research ( Site 0008)

Ocala, Florida, United States

Triple O Research Institute, P.A. ( Site 0026)

West Palm Beach, Florida, United States

...and 68 more locations

Geometric Mean Fold Rise in Serotype-specific OPA Day 1 to Day 30

Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using a Multiplex Opsonophagocytic Assay. Geometric mean fold rise (GMFR) is the geometric mean of fold rise from baseline to postvaccination.

Time frame: Day 1 (Baseline) and Day 30

GMFR in Serotype-specific IgG Day 1 to Day 30

IgG for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using an electrochemiluminescence assay. GMFR is the geometric mean of fold rise from baseline to postvaccination.

Time frame: Day 1 (Baseline) and Day 30

Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Day 1 to Day 30

Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using a Multiplexed Opsonophagocytic Assay. The percentage of participants who had ≥4-fold rise in OPA titers were calculated from baseline to postvaccination.

Time frame: Day 1 (Baseline) and Day 30

Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Day 1 to Day 30

IgG for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using an electrochemiluminescence assay. The percentage of participants who had ≥ 4-fold rise in IgG concentration are calculated from baseline to postvaccination.

Time frame: Day 1 (Baseline) and Day 30

Geometric Mean Titer of Serotype-specific OPA at Month 7

The geometric mean titer (GMT) of serotype-specific OPA for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using a multiplex opsonophagocytic assay. The within-group 95% CIs are obtained by exponentiating the CIs of the mean of the natural log values based on the t-distribution.

Time frame: Month 7

Geometric Mean Concentration of Serotype-specific IgG at Month 7

Time frame: Month 7

GMFR in Serotype-specific OPA Day 1 to Month 7

Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using a Multiplexed Opsonophagocytic Assay. Geometric mean fold rise (GMFR) is the geometric mean of fold rise from baseline to postvaccination.

Time frame: Day 1 (Baseline) and Month 7

GMFR in Serotype-specific IgG Day 1 to Month 7

Time frame: Day 1 (Baseline) and Month 7

Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Day 1 to Month 7

Time frame: Day 1 (Baseline) and Month 7

Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Day 1 to Month 7

IgG for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using an electrochemiluminescence assay. The percentage of participants who had ≥ 4-fold rise in IgG concentration are calculated from baseline to postvaccination.

Time frame: Day 1 (Baseline) and Month 7

GMFR in Serotype-specific OPA Month 6 to Month 7

Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using the Multiplexed Opsonophagocytic Assay. Geometric mean fold rise (GMFR) is the geometric mean of fold rise from baseline to postvaccination.

Time frame: Month 6 (Baseline before Vaccination 2) and Month 7

GMFR in Serotype-specific IgG Month 6 to Month 7

IgG for the serotypes contained in Prevnar 13™ and V114 and (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using an electrochemiluminescence assay. GMFR is the geometric mean of fold rise from baseline to postvaccination.

Time frame: Month 6 (Baseline before Vaccination 2) and Month 7

Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Month 6 to Month 7

Time frame: Month 6 (Baseline before Vaccination 2) and Month 7

Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Month 6 to Month 7

IgG for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using an electrochemiluminescence assay. The percentage of participants who had ≥ 4-fold rise in IgG concentration are calculated from baseline to postvaccination.

Time frame: Month 6 (Baseline before Vaccination 2) and Month 7