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)

Pneumococcal Infections Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03547167
• Other study ID #: V114-017
• Secondary ID: 2017-004915-38V1
• Status: Completed
• Phase: Phase 3
• Start date: July 16, 2018
• Est. completion date: January 20, 2020

Study information

• Verified date: December 2020
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1515
• Est. completion date: January 20, 2020
• Est. primary completion date: January 20, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 49 Years

Eligibility

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.

Related Conditions & MeSH terms

• Pneumococcal Infections

Intervention

Biological:
• 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™
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™23
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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Chile,  New Zealand,  Poland,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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)
Primary	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	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.	Up to 5 days after Vaccination 2 (Month 6)
Secondary	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.	Up to 14 days after Vaccination 2 (Month 6)
Secondary	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.	From Month 6 (before Vaccination 2) to Month 7
Secondary	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.	Day 30
Secondary	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.	Day 1 (Baseline) and Day 30
Secondary	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.	Day 1 (Baseline) and Day 30
Secondary	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.	Day 1 (Baseline) and Day 30
Secondary	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.	Day 1 (Baseline) and Day 30
Secondary	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.	Month 7
Secondary	Geometric Mean Concentration of Serotype-specific IgG at Month 7	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.	Month 7
Secondary	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.	Day 1 (Baseline) and Month 7
Secondary	GMFR 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. GMFR is the geometric mean of fold rise from baseline to postvaccination.	Day 1 (Baseline) and Month 7
Secondary	Percentage of Participants With =4-Fold Rise 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. The percentage of participants who had =4-fold rise in OPA titers were calculated from baseline to postvaccination.	Day 1 (Baseline) and Month 7
Secondary	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.	Day 1 (Baseline) and Month 7
Secondary	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.	Month 6 (Baseline before Vaccination 2) and Month 7
Secondary	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.	Month 6 (Baseline before Vaccination 2) and Month 7
Secondary	Percentage of Participants With =4-Fold Rise 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 a Multiplexed Opsonophagocytic Assay. The percentage of participants who had =4-fold rise in OPA titers were calculated from baseline to postvaccination.	Month 6 (Baseline before Vaccination 2) and Month 7
Secondary	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.	Month 6 (Baseline before Vaccination 2) and Month 7