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)

NCT03547167 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: V114-0172017-004915-38
• Study Type: interventional
• Target: 1,515
• Locations: 7 countries
• Sites: 78

Brief 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.

Conditions

Pneumococcal Infections

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  Day 30

Secondary Outcomes (18)

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

  Up to 5 days after Vaccination 2 (Month 6)

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

  Up to 14 days after Vaccination 2 (Month 6)

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

  From Month 6 (before Vaccination 2) to Month 7

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

  Day 30

• Geometric Mean Fold Rise in Serotype-specific OPA 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 6 (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 6 (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 aluminum) 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: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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) \<10%
• Chronic liver disease with documented history of compensated cirrhosis (Child-Pugh Score A)
• Confirmed diagnosis of Chronic Obstructive Pulmonary Disease (COPD) with spirometric Global Initiative for Chronic Obstructive Lung Disease Stage 1 to 3
• Confirmed diagnosis of mild or moderate persistent asthma receiving guideline directed therapy
• 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.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (78)

Chinle Comprehensive Health Care Facility ( Site 0001)

Chinle, Arizona, 86503, United States

Location

Fort Defiance Center for American Indian Health ( Site 0002)

Fort Defiance, Arizona, 86504, United States

Location

Pulmonary Associates, PA ( Site 0043)

Glendale, Arizona, 85306, United States

Location

Central Phoenix Medical Clinic, LLC ( Site 0031)

Phoenix, Arizona, 85020, United States

Location

Whiteriver Center for American Indian Health ( Site 0005)

Whiteriver, Arizona, 85941, United States

Location

Inland Empire Clinical Trials, LLC ( Site 0052)

Rialto, California, 92377, United States

Location

Top Medical Research, Inc ( Site 0033)

Cutler Bay, Florida, 33189, United States

Location

Indago Research & Health Center, Inc ( Site 0054)

Hialeah, Florida, 33012, United States

Location

Renstar Medical Research ( Site 0008)

Ocala, Florida, 34471, United States

Location

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

West Palm Beach, Florida, 33407, United States

Location

Emory University School of Medicine at Grady Hospital ( Site 0027)

Atlanta, Georgia, 30303, United States

Location

Kootenai Health ( Site 0042)

Coeur d'Alene, Idaho, 83814, United States

Location

Evanston Premier Healthcare & Research, LLC. ( Site 0012)

Evanston, Illinois, 60201, United States

Location

Pharmakon Inc ( Site 0049)

Evergreen Park, Illinois, 60805, United States

Location

Reid Physician Associates ( Site 0055)

Richmond, Indiana, 47374, United States

Location

The Center for Pharmaceutical Research PC ( Site 0050)

Kansas City, Missouri, 64114, United States

Location

Clinical Research Consortium ( Site 0053)

Las Vegas, Nevada, 89119, United States

Location

Internal Medicine Associates [Bridgeton, NJ] ( Site 0015)

Bridgeton, New Jersey, 08302, United States

Location

Gallup Center for American Indian Health ( Site 0003)

Gallup, New Mexico, 87301, United States

Location

Shiprock Center for American Indian Health ( Site 0004)

Shiprock, New Mexico, 87420, United States

Location

Corning Center For Clinical Research ( Site 0036)

Corning, New York, 14830, United States

Location

Mid Hudson Medical Research ( Site 0022)

New Windsor, New York, 12553, United States

Location

Wake Research Associates, LLC ( Site 0016)

Raleigh, North Carolina, 27612, United States

Location

Lehigh Valley Health Network ( Site 0040)

Allentown, Pennsylvania, 18102, United States

Location

University of Pennsylvania ( Site 0030)

Philadelphia, Pennsylvania, 19104, United States

Location

Mountain View Clinical Research ( Site 0007)

Greer, South Carolina, 29651, United States

Location

Holston Medical Group ( Site 0025)

Kingsport, Tennessee, 37660, United States

Location

AIM Trials ( Site 0060)

Fort Worth, Texas, 76104, United States

Location

University of Texas Medical Branch at Galveston ( Site 0034)

Galveston, Texas, 77555-1115, United States

Location

Private Practice Leadership, LLC ( Site 0051)

Houston, Texas, 77094, United States

Location

Texas Center For Drug Development ( Site 0041)

Houston, Texas, 77801, United States

Location

Texas Institute Of Cardiology ( Site 0048)

McKinney, Texas, 75071, United States

Location

Village Health Partners ( Site 0006)

Plano, Texas, 75024, United States

Location

Copperview Medical Center ( Site 0038)

South Jordan, Utah, 84095, United States

Location

Timber Lane Allergy & Asthma Research, LLC ( Site 0044)

South Burlington, Vermont, 05403, United States

Location

Pulmonary & Sleep Research ( Site 0046)

Spokane Valley, Washington, 99216, United States

Location

Gundersen Health System ( Site 0021)

La Crosse, Wisconsin, 54601, United States

Location

Marshfield Clinic ( Site 0013)

Marshfield, Wisconsin, 54449, United States

Location

Paratus Clinical Pty Ltd - Blacktown Clinic ( Site 0174)

Blacktown, New South Wales, 2148, Australia

Location

Holdsworth House Medical Practice ( Site 0170)

Sydney, New South Wales, 2010, Australia

Location

Core Research Group Pty limited ( Site 0175)

Brisbane, Queensland, 4064, Australia

Location

Emeritus Research Pty Ltd ( Site 0173)

Camberwell, Victoria, 3124, Australia

Location

Paratus Clinical Kanwal ( Site 0172)

Kanwal, 2259, Australia

Location

Nepean Hospital ( Site 0176)

Kingswood, 2747, Australia

Location

The Liver and Intestinal Research Centre (LAIR) ( Site 0302)

Vancouver, British Columbia, V5Z 1H2, Canada

Location

GA Research Associates, Ltd/Ltee ( Site 0303)

Moncton, New Brunswick, E1G 1A7, Canada

Location

Colchester Research Group ( Site 0094)

Truro, Nova Scotia, B2N 1L2, Canada

Location

Hamilton Medical Research Group ( Site 0092)

Hamilton, Ontario, L8M 1K7, Canada

Location

SKDS Research Inc. ( Site 0099)

Newmarket, Ontario, L3Y 5G8, Canada

Location

Omnispec Recherche Clinique Inc ( Site 0093)

Mirabel, Quebec, J7J 2K8, Canada

Location

Dynamik Research ( Site 0095)

Pointe-Claire, Quebec, H9R 3J1, Canada

Location

Diex Recherche Quebec Inc ( Site 0091)

Québec, Quebec, G1N 4V3, Canada

Location

Q & T Research Sherbrooke Inc. ( Site 0097)

Sherbrooke, Quebec, J1J 2G2, Canada

Location

Clinica Arauco Salud ( Site 0100)

Santiago, RM, 7560994, Chile

Location

Centro de Investigacion Clinica UC CICUC ( Site 0104)

Santiago, 8330034, Chile

Location

CECIM ( Site 0101)

Santiago, 8330336, Chile

Location

CESFAM Esmeralda ( Site 0102)

Santiago, 9351603, Chile

Location

Hospital Dr. Hernan Henriquez Aravena ( Site 0105)

Temuco, 4781151, Chile

Location

Southern Clinical Trials - Waitemata ( Site 0183)

Auckland, 0626, New Zealand

Location

Auckland Clinical Studies Limited ( Site 0189)

Auckland, 1010, New Zealand

Location

Optimal Clinical Trials ( Site 0182)

Auckland, 1010, New Zealand

Location

Christchurch Heart Institute ( Site 0280)

Christchurch, 8011, New Zealand

Location

Southern Clinical Trials Ltd ( Site 0180)

Christchurch, 8013, New Zealand

Location

Lakeland Clinical Trials ( Site 0181)

Rotorua, 3010, New Zealand

Location

Bay of Plenty Clinical School ( Site 0186)

Tauranga, 3143, New Zealand

Location

P3 Research Ltd - Wellington ( Site 0184)

Wellington, 6021, New Zealand

Location

WSOZ im.T.Browicza w Bydgoszczy ( Site 0317)

Bydgoszcz, 85-030, Poland

Location

Centrum Medyczne Pratia Bydgoszcz ( Site 0139)

Bydgoszcz, 85-796, Poland

Location

Synexus Polska Sp. z o.o. ( Site 0238)

Gdansk, 80-382, Poland

Location

Specjalistyczny osrodek .All-Med. Grazyna Pulka ( Site 0233)

Krakow, 30-033, Poland

Location

ID Clinic ( Site 0235)

Mysłowice, 41-400, Poland

Location

Centrum Medyczne Ogrodowa Sp. Z o.o. ( Site 0319)

Skierniewice, 96-100, Poland

Location

Niepubliczny Zaklad Opieki Zdrowotnej ( Site 0314)

Sopot, 81-717, Poland

Location

Wroclawskie Centrum Zdrowia SP ZOZ ( Site 0236)

Wroclaw, 50-136, Poland

Location

Synexus Polska Sp. z o.o. oddział we Wrocławiu ( Site 0234)

Wroclaw, 50-381, Poland

Location

Republican Clinical Hospital of Infectious Diseases n. a. A.F.Agafonov ( Site 0249)

Kazan', 420140, Russia

Location

Saratov State Medical University n.a. V.I.Razumovskiy ( Site 0144)

Saratov, 410054, Russia

Location

Smolensk State Medical University ( Site 0246)

Smolensk, 214019, Russia

Location

Related Publications (1)

• Hammitt LL, Quinn D, Janczewska E, Pasquel FJ, Tytus R, Rajender Reddy K, Abarca K, Khaertynova IM, Dagan R, McCauley J, Cheon K, Pedley A, Sterling T, Tamms G, Musey L, Buchwald UK. Immunogenicity, Safety, and Tolerability of V114, a 15-Valent Pneumococcal Conjugate Vaccine, in Immunocompetent Adults Aged 18-49 Years With or Without Risk Factors for Pneumococcal Disease: A Randomized Phase 3 Trial (PNEU-DAY). Open Forum Infect Dis. 2021 Dec 18;9(3):ofab605. doi: 10.1093/ofid/ofab605. eCollection 2022 Mar.

  PMID: 35146039 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: May 24, 2018
• First Posted: June 6, 2018
• Study Start: July 16, 2018
• Primary Completion: January 20, 2020
• Study Completion: January 20, 2020
• Last Updated: January 15, 2021
• Results First Posted: January 15, 2021

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will share

Locations

CA (9); CL (5); PL (9); NZ (8); RU (3); US (38); AU (6)