Clinical trial NCT03547167: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumococcal Infections
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2018-06-06
Enrollment: 1515
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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:

  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.

Primary outcomes:
measure: Percentage of Participants With Solicited Injection-site Adverse Events Following V114 or Prevnar 13™
timeFrame: Up to 5 days after Vaccination 1
measure: Percentage of Participants With Solicited Systemic Adverse Events Following V114 or Prevnar 13™
timeFrame: Up to 14 days after Vaccination 1
measure: Percentage of Participants With a Vaccine-related Serious Adverse Event Following V114 or Prevnar 13™
timeFrame: Up to Month 6 (before Vaccination 2)
measure: Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity Day 30 Following V114 or Prevnar 13™
timeFrame: Day 30
Secondary outcomes:
measure: Percentage of Participants With Solicited Injection-site Adverse Events Following PNEUMOVAX™23
timeFrame: Up to 5 days after Vaccination 2 (Month 6)
measure: Percentage of Participants With Solicited Systemic Adverse Events Following PNEUMOVAX™23
timeFrame: Up to 14 days after Vaccination 2 (Month 6)
measure: Percentage of Participants With a Vaccine-related Serious Adverse Event Following PNEUMOVAX™23
timeFrame: From Month 6 (before Vaccination 2) to Month 7
measure: Geometric Mean Concentration of Serotype-specific Immunoglobulin G at Day 30
timeFrame: Day 30
measure: Geometric Mean Fold Rise in Serotype-specific OPA Day 1 to Day 30
timeFrame: Day 1 (Baseline) and Day 30
measure: GMFR in Serotype-specific IgG Day 1 to Day 30
timeFrame: Day 1 (Baseline) and Day 30
measure: Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Day 1 to Day 30
timeFrame: Day 1 (Baseline) and Day 30
measure: Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Day 1 to Day 30
timeFrame: Day 1 (Baseline) and Day 30
measure: Geometric Mean Titer of Serotype-specific OPA at Month 7
timeFrame: Month 7
measure: Geometric Mean Concentration of Serotype-specific IgG at Month 7
timeFrame: Month 7
measure: GMFR in Serotype-specific OPA Day 1 to Month 7
timeFrame: Day 1 (Baseline) and Month 7
measure: GMFR in Serotype-specific IgG Day 1 to Month 7
timeFrame: Day 1 (Baseline) and Month 7
measure: Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Day 1 to Month 7
timeFrame: Day 1 (Baseline) and Month 7
measure: Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Day 1 to Month 7
timeFrame: Day 1 (Baseline) and Month 7
measure: GMFR in Serotype-specific OPA Month 6 to Month 7
timeFrame: Month 6 (Baseline before Vaccination 2) and Month 7
measure: GMFR in Serotype-specific IgG Month 6 to Month 7
timeFrame: Month 6 (Baseline before Vaccination 2) and Month 7
measure: Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Month 6 to Month 7
timeFrame: Month 6 (Baseline before Vaccination 2) and Month 7
measure: Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Month 6 to Month 7
timeFrame: Month 6 (Baseline before Vaccination 2) and Month 7
Other outcomes:
Locations:
city: Chinle
country: United States
facility: Chinle Comprehensive Health Care Facility ( Site 0001)
state: Arizona
city: Fort Defiance
country: United States
facility: Fort Defiance Center for American Indian Health ( Site 0002)
state: Arizona
city: Glendale
country: United States
facility: Pulmonary Associates, PA ( Site 0043)
state: Arizona
city: Phoenix
country: United States
facility: Central Phoenix Medical Clinic, LLC ( Site 0031)
state: Arizona
city: Whiteriver
country: United States
facility: Whiteriver Center for American Indian Health ( Site 0005)
state: Arizona
city: Rialto
country: United States
facility: Inland Empire Clinical Trials, LLC ( Site 0052)
state: California
city: Cutler Bay
country: United States
facility: Top Medical Research, Inc ( Site 0033)
state: Florida
city: Hialeah
country: United States
facility: Indago Research & Health Center, Inc ( Site 0054)
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research ( Site 0008)
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute, P.A. ( Site 0026)
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine at Grady Hospital ( Site 0027)
state: Georgia
city: Coeur d'Alene
country: United States
facility: Kootenai Health ( Site 0042)
state: Idaho
city: Evanston
country: United States
facility: Evanston Premier Healthcare & Research, LLC. ( Site 0012)
state: Illinois
city: Evergreen Park
country: United States
facility: Pharmakon Inc ( Site 0049)
state: Illinois
city: Richmond
country: United States
facility: Reid Physician Associates ( Site 0055)
state: Indiana
city: Kansas City
country: United States
facility: The Center for Pharmaceutical Research PC ( Site 0050)
state: Missouri
city: Las Vegas
country: United States
facility: Clinical Research Consortium ( Site 0053)
state: Nevada
city: Bridgeton
country: United States
facility: Internal Medicine Associates [Bridgeton, NJ] ( Site 0015)
state: New Jersey
city: Gallup
country: United States
facility: Gallup Center for American Indian Health ( Site 0003)
state: New Mexico
city: Shiprock
country: United States
facility: Shiprock Center for American Indian Health ( Site 0004)
state: New Mexico
city: Corning
country: United States
facility: Corning Center For Clinical Research ( Site 0036)
state: New York
city: New Windsor
country: United States
facility: Mid Hudson Medical Research ( Site 0022)
state: New York
city: Raleigh
country: United States
facility: Wake Research Associates, LLC ( Site 0016)
state: North Carolina
city: Allentown
country: United States
facility: Lehigh Valley Health Network ( Site 0040)
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania ( Site 0030)
state: Pennsylvania
city: Greer
country: United States
facility: Mountain View Clinical Research ( Site 0007)
state: South Carolina
city: Kingsport
country: United States
facility: Holston Medical Group ( Site 0025)
state: Tennessee
city: Fort Worth
country: United States
facility: AIM Trials ( Site 0060)
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch at Galveston ( Site 0034)
state: Texas
city: Houston
country: United States
facility: Private Practice Leadership, LLC ( Site 0051)
state: Texas
city: Houston
country: United States
facility: Texas Center For Drug Development ( Site 0041)
state: Texas
city: McKinney
country: United States
facility: Texas Institute Of Cardiology ( Site 0048)
state: Texas
city: Plano
country: United States
facility: Village Health Partners ( Site 0006)
state: Texas
city: South Jordan
country: United States
facility: Copperview Medical Center ( Site 0038)
state: Utah
city: South Burlington
country: United States
facility: Timber Lane Allergy & Asthma Research, LLC ( Site 0044)
state: Vermont
city: Spokane Valley
country: United States
facility: Pulmonary & Sleep Research ( Site 0046)
state: Washington
city: La Crosse
country: United States
facility: Gundersen Health System ( Site 0021)
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic ( Site 0013)
state: Wisconsin
city: Blacktown
country: Australia
facility: Paratus Clinical Pty Ltd - Blacktown Clinic ( Site 0174)
state: New South Wales
city: Sydney
country: Australia
facility: Holdsworth House Medical Practice ( Site 0170)
state: New South Wales
city: Brisbane
country: Australia
facility: Core Research Group Pty limited ( Site 0175)
state: Queensland
city: Camberwell
country: Australia
facility: Emeritus Research Pty Ltd ( Site 0173)
state: Victoria
city: Kanwal
country: Australia
facility: Paratus Clinical Kanwal ( Site 0172)
city: Kingswood
country: Australia
facility: Nepean Hospital ( Site 0176)
city: Vancouver
country: Canada
facility: The Liver and Intestinal Research Centre (LAIR) ( Site 0302)
state: British Columbia
city: Moncton
country: Canada
facility: GA Research Associates, Ltd/Ltee ( Site 0303)
state: New Brunswick
city: Truro
country: Canada
facility: Colchester Research Group ( Site 0094)
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton Medical Research Group ( Site 0092)
state: Ontario
city: Newmarket
country: Canada
facility: SKDS Research Inc. ( Site 0099)
state: Ontario
city: Mirabel
country: Canada
facility: Omnispec Recherche Clinique Inc ( Site 0093)
state: Quebec
city: Pointe-Claire
country: Canada
facility: Dynamik Research ( Site 0095)
state: Quebec
city: Sherbrooke
country: Canada
facility: Q & T Research Sherbrooke Inc. ( Site 0097)
state: Quebec
city: Quebec
country: Canada
facility: Diex Recherche Quebec Inc ( Site 0091)
city: Santiago
country: Chile
facility: Clinica Arauco Salud ( Site 0100)
state: RM
city: Santiago
country: Chile
facility: Centro de Investigacion Clinica UC CICUC ( Site 0104)
city: Santiago
country: Chile
facility: CECIM ( Site 0101)
city: Santiago
country: Chile
facility: CESFAM Esmeralda ( Site 0102)
city: Temuco
country: Chile
facility: Hospital Dr. Hernan Henriquez Aravena ( Site 0105)
city: Auckland
country: New Zealand
facility: Southern Clinical Trials - Waitemata ( Site 0183)
city: Auckland
country: New Zealand
facility: Auckland Clinical Studies Limited ( Site 0189)
city: Auckland
country: New Zealand
facility: Optimal Clinical Trials ( Site 0182)
city: Christchurch
country: New Zealand
facility: Christchurch Heart Institute ( Site 0280)
city: Christchurch
country: New Zealand
facility: Southern Clinical Trials Ltd ( Site 0180)
city: Rotorua
country: New Zealand
facility: Lakeland Clinical Trials ( Site 0181)
city: Tauranga
country: New Zealand
facility: Bay of Plenty Clinical School ( Site 0186)
city: Wellington
country: New Zealand
facility: P3 Research Ltd - Wellington ( Site 0184)
city: Bydgoszcz
country: Poland
facility: WSOZ im.T.Browicza w Bydgoszczy ( Site 0317)
city: Bydgoszcz
country: Poland
facility: Centrum Medyczne Pratia Bydgoszcz ( Site 0139)
city: Gdansk
country: Poland
facility: Synexus Polska Sp. z o.o. ( Site 0238)
city: Krakow
country: Poland
facility: Specjalistyczny osrodek .All-Med. Grazyna Pulka ( Site 0233)
city: Myslowice
country: Poland
facility: ID Clinic ( Site 0235)
city: Skierniewice
country: Poland
facility: Centrum Medyczne Ogrodowa Sp. Z o.o. ( Site 0319)
city: Sopot
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej ( Site 0314)
city: Wroclaw
country: Poland
facility: Wroclawskie Centrum Zdrowia SP ZOZ ( Site 0236)
city: Wroclaw
country: Poland
facility: Synexus Polska Sp. z o.o. oddział we Wrocławiu ( Site 0234)
city: Kazan
country: Russian Federation
facility: Republican Clinical Hospital of Infectious Diseases n. a. A.F.Agafonov ( Site 0249)
city: Saratov
country: Russian Federation
facility: Saratov State Medical University n.a. V.I.Razumovskiy ( Site 0144)
city: Smolensk
country: Russian Federation
facility: Smolensk State Medical University ( Site 0246)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.