A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 Followed by PNEUMOVAX™23 in Healthy Adults 50 Years of Age or Older (V114-016/PNEU-PATH)

NCT03480763 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: V114-0162017-004024-30
• Study Type: interventional
• Target: 652
• Locations: 4 countries
• Sites: 22

Brief Summary

This study is designed 1) to evaluate the safety, tolerability, and immunogenicity of V114 and Prevnar 13™, 2) to describe the safety of sequential administration of V114 or Prevnar 13™ followed by PNEUMOVAX™23, and 3) to evaluate the immune responses to the 15 serotypes contained in V114 when PNEUMOVAX™23 is given approximately 12 months after receipt of either V114 or Prevnar 13™ in healthy adults 50 years of age or older. There was no formal hypothesis testing.

Conditions

Pneumococcal Infections

Outcome Measures

Primary Outcomes (7)

• 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 treatment, whether or not considered related to the study treatment. Following vaccination with 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.

  Up to 5 days after Vaccination 1

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

  An 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 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.

  Up to 5 days after Vaccination 2

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

  An 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 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.

  Up to 14 days after Vaccination 1

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

  An 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 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.

  Up to 14 days after Vaccination 2

• Percentage of Participants With Vaccine-related Serious Adverse Events 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 will be determined by the investigator. Following vaccination with V114 or Prevnar 13™, the percentage of participants with vaccine-related serious adverse events was assessed.

  Up to 12 months after Vaccination 1

• Percentage of Participants With Vaccine-related Serious Adverse Events 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 will be determined by the investigator. Following vaccination with PNEUMOVAX™23, the percentage of participants with vaccine-related serious adverse events was assessed.

  Month 12 to Month 13 (Up to 44 days after Vaccination 2)

• Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity at 30 Days Following PNEUMOVAX™23

  Serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) (estimated) and GMT ratios with 95% confidence intervals (CIs) were calculated using a constrained longitudinal data analysis (cLDA) model utilizing data from both vaccination groups. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the GMT ratios); within-group CIs were not calculated. OPA for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) will be determined using a Multiplexed Opsonophagocytic Assay.

  Month 13 (30 days after Vaccination 2)

Secondary Outcomes (21)

• Geometric Mean Concentration of Serotype-specific Immunoglobulin G at 30 Days Following PNEUMOVAX™23

  Month 13 (30 days after Vaccination 2)

• GMT of Serotype-specific OPA at Day 30

  Day 30

• GMC of Serotype-specific IgG at Day 30

  Day 30

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

  Day 1 (Baseline) and Day 30

• GMFR in Serotype-specific IgG Day 1 to Day 30

  Day 1 (Baseline) and Day 30

Study Arms (2)

V114

EXPERIMENTAL

Participants will receive a single 0.5 mL intramuscular (IM) injection of V114 on Day 1 (Vaccination 1) and a single 0.5 mL IM injection of PNEUMOVAX™23 at Month 12 (Vaccination 2)

Biological: V114; Biological: PNEUMOVAX™23

Prevnar 13™

ACTIVE COMPARATOR

Participants will receive a single 0.5 mL IM injection of Prevnar 13™ on Day 1 (Vaccination 1) and a single 0.5 mL IM injection of PNEUMOVAX™23 at Month 12 (Vaccination 2)

Biological: Prevnar 13™; Biological: PNEUMOVAX™23

Interventions

V114 BIOLOGICAL

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

V114

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) in each 0.5 mL dose

Also known as: PCV13

Prevnar 13™

PNEUMOVAX™23 BIOLOGICAL

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

Also known as: PPV23

Prevnar 13™; V114

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female in good health
• 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 administration of last study vaccine.

You may not qualify if:

• History of invasive pneumococcal disease
• Known hypersensitivity to any component of pneumococcal polysaccharide vaccine, pneumococcal conjugate vaccine, or any diphtheria toxoid-containing vaccine.
• Known or suspected impairment of immune function
• Coagulation disorder contraindicating intramuscular vaccination
• History of malignancy ≤5 years before enrollment, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
• 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 intervention at least 30 days before study entry.
• Received systemic corticosteroids exceeding physiologic replacement doses (approximately 5 mg/day prednisone equivalent) within 14 days before vaccination. (Note: Topical, ophthalmic, intra-articular or soft-tissue \[e.g., bursa, tendon steroid injections\], and inhaled/nebulized steroids are permitted).
• Received immunosuppressive therapy
• Received a blood transfusion or blood products within 6 months of enrollment
• Participated in another clinical study of an investigational product within 2 months of enrollment
• Current user of recreational or illicit drugs or history of drug or alcohol abuse or dependence.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (22)

East Valley Family Physicians ( Site 0104)

Chandler, Arizona, 85224, United States

Location

Central Phoenix Medical Clinic, LLC ( Site 0125)

Phoenix, Arizona, 85020, United States

Location

Encompass Clinical Research ( Site 0118)

Spring Valley, California, 91978, United States

Location

Diablo Clinical Research, Inc ( Site 0132)

Walnut Creek, California, 94598, United States

Location

Clinical Research of South Florida ( Site 0126)

Coral Gables, Florida, 33134, United States

Location

QPS Miami Research Associates ( Site 0116)

South Miami, Florida, 33143, United States

Location

Heartland Research Associates, Llc ( Site 0115)

Wichita, Kansas, 67207, United States

Location

Centennial Medical Group ( Site 0109)

Elkridge, Maryland, 21075, United States

Location

Rapid Medical Research, Inc. ( Site 0119)

Cleveland, Ohio, 44122, United States

Location

University of Texas Medical Branch at Galveston ( Site 0127)

Galveston, Texas, 77555-1115, United States

Location

Texas Center For Drug Development ( Site 0107)

Houston, Texas, 77081, United States

Location

Diagnostics Research Group ( Site 0100)

San Antonio, Texas, 78229, United States

Location

J Lewis Research Inc / Foothill Family Clinic ( Site 0123)

Salt Lake City, Utah, 84109, United States

Location

J Lewis Research Inc/Jordan River Family Medicine ( Site 0114)

South Jordan, Utah, 84095, United States

Location

Health Research of Hampton Roads, Inc. ( Site 0106)

Newport News, Virginia, 23606, United States

Location

Seoul National University Hospital ( Site 0400)

Seoul, 03080, South Korea

Location

Korea University Guro Hospital ( Site 0401)

Seoul, 08308, South Korea

Location

CAP Centelles ( Site 0303)

Centelles, Barcelona, 08540, Spain

Location

Instituto de Ciencias Medicas.ICM ( Site 0301)

Alicante, 03004, Spain

Location

Fundacion Oftalmologica del Mediterraneo ( Site 0300)

Valencia, 46015, Spain

Location

National Cheng Kung University Hospital ( Site 0502)

Dawan, 70403, Taiwan

Location

National Taiwan University Hospital ( Site 0500)

Taipei, 100, Taiwan

Location

Related Publications (2)

• Song JY, Chang CJ, Andrews C, Diez-Domingo J, Oh MD, Dagan R, Hartzel J, Pedley A, Li J, Sterling T, Tamms G, Chiarappa JA, Lutkiewicz J, Musey L, Tu Y, Buchwald UK; V114-016 (PNEU-PATH) study group. Safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, followed by sequential PPSV23 vaccination in healthy adults aged >/=50 years: A randomized phase III trial (PNEU-PATH). Vaccine. 2021 Oct 15;39(43):6422-6436. doi: 10.1016/j.vaccine.2021.08.038. Epub 2021 Sep 4.

  PMID: 34489128 RESULT

• Huang L, Yang X, Li H, Xie Z, Zhu T, You W, Wang Z, Tan J, Feng G, Sun Q, Wang B, Han X, Wang Y. Immune persistence of a single dose of 23-valent pneumococcal polysaccharide vaccine: A 6-year follow-up. Hum Vaccin Immunother. 2025 Dec;21(1):2517489. doi: 10.1080/21645515.2025.2517489. Epub 2025 Jun 19.

  PMID: 40537903 DERIVED

MeSH Terms

Conditions

Pneumococcal Infections

Interventions

13-valent pneumococcal vaccine

Condition Hierarchy (Ancestors)

Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2018
• First Posted: March 29, 2018
• Study Start: June 22, 2018
• Primary Completion: December 23, 2019
• Study Completion: December 23, 2019
• Last Updated: November 2, 2021
• Results First Posted: January 6, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share

Locations

KR (2); ES (3); US (15); TW (2)