Safety and Immunogenicity of V114 in Healthy Adults (V114-019/PNEU-AGE)

Pneumococcal Infections Clinical Trial

— PNEU-AGE  

Official title:

A Phase 3, Multicenter, Randomized, Double-blind, Active Comparator-controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Healthy Adults 50 Years of Age or Older (PNEU-AGE)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03950622
• Other study ID #: V114-019
• Secondary ID: 2018-004316-22V1
• Status: Completed
• Phase: Phase 3
• Start date: June 13, 2019
• Est. completion date: March 30, 2020

Study information

• Verified date: March 2021
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to 1) evaluate the safety and tolerability of V114 and 2) to compare the immune responses of the 15 serotypes contained in V114 with V114 versus Prevnar 13™. The primary hypotheses are that 1) V114 is noninferior to Prevnar 13™ as measured by the serotype specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) for 13 shared serotypes at 30 days postvaccination and that 2) V114 is superior to Prevnar 13™ as measured by serotype-specific OPA GMTs for 2 unique serotypes in V114 at 30 days postvaccination.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1205
• Est. completion date: March 30, 2020
• Est. primary completion date: March 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Participant has good health in the opinion of the investigator. Any underlying chronic condition must be documented to be in stable condition according to the investigator's judgment.

• Male or female =50 years of age at the time of signing the informed consent. (For Japan only: Is male or female =65 years of age at the time of signing the informed consent)

• Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

• Female participant is eligible to participate if she is not pregnant, not breastfeeding, and is not a woman of childbearing potential (WOCBP) OR a WOCBP who agrees to use agreed upon contraception during the treatment period and for at least 6 weeks after the last dose of study intervention.

• Provides written informed consent for the study. The participant may also provide consent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research.

Exclusion Criteria:

• History of invasive pneumococcal disease (IPD) (positive blood culture, positive cerebrospinal fluid culture, or positive culture at another sterile site) or known history of other culture-positive pneumococcal disease within 3 years of Visit 1 (Day 1).

• Known hypersensitivity to any component of pneumococcal polysaccharide vaccine, pneumococcal conjugate vaccine (PCV), or any diphtheria toxoid-containing vaccine.

• Known or suspected impairment of immunological function including, but not limited to, a history of congenital or acquired immunodeficiency, documented human immunodeficiency virus (HIV) infection, functional or anatomic asplenia, or history of autoimmune disease.

• Coagulation disorder contraindicating intramuscular (IM) vaccinations.

• Recent febrile illness (defined as oral or tympanic temperature =100.4°F [=38.0°C] or axillary or temporal temperature =99.4°F [=37.4°C]) or received antibiotic therapy for any acute illness occurring within 72 hours before receipt of study vaccine.

• History of malignancy =5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.

• A WOCBP who has a positive urine or serum pregnancy test before the first vaccination at Visit 1 (Day 1).

• Has received any pneumococcal vaccine or is expected to receive any pneumococcal vaccine during the study outside of the protocol.

• Has 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.

• Has 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.)

• Is receiving immunosuppressive therapy, including chemotherapeutic agents used to treat cancer or other conditions, and interventions associated with organ or bone marrow transplantation, or autoimmune disease.

• Has received any non-live vaccine within the 14 days before receipt of any study vaccine or is scheduled to receive any non-live vaccine within 30 days following receipt of any study vaccine. (Exception: Inactivated influenza vaccine may be administered but must be given at least 7 days before receipt of any study vaccine or at least 15 days after receipt of any study vaccine.)

• Has 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.

• Has received a blood transfusion or blood products, including immunoglobulin, within the 6 months before receipt of study vaccine or is scheduled to receive a blood transfusion or blood product within 30 days of receipt of study vaccine. Autologous blood transfusions are not considered an exclusion criterion.

• Currently participating in or has participated in an interventional clinical study with an investigational compound or device within 2 months of participating in this current study.

• In the opinion of the investigator, has a history of clinically relevant drug or alcohol use that would interfere with participation in protocol-specified activities.

• History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might expose the participant to risk by participating in the study, confound the results of the study, or interfere with the participant's participation for the full duration of the study.

• An immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study.

Related Conditions & MeSH terms

• Pneumococcal Infections

Intervention

Biological:
• V114
15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F in each 0.5 mL dose.
• Prevnar 13®
13-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F in each 0.5 mL dose.

Locations

Country	Name	City	State
Canada	Milestone Research ( Site 2003)	London	Ontario
Canada	Dynamik Research ( Site 2000)	Pointe-Claire	Quebec
Canada	Bluewater Clinical Research Group Inc ( Site 2004)	Sarnia	Ontario
Canada	Q & T Research Sherbrooke Inc. ( Site 2001)	Sherbrooke	Quebec
Canada	Manna Research Inc.. ( Site 2007)	Toronto	Ontario
Canada	Colchester Research Group ( Site 2002)	Truro	Nova Scotia
Japan	Souseikai PS Clinic ( Site 0402)	Fukuoka
Japan	P-One Clinic, Keikokai Medical Corp. ( Site 0400)	Hachioji	Tokyo
Japan	Souseikai Nishikumamoto Hospital ( Site 0404)	Kumamoto
Japan	Medical Corporation Heishinkai OPHAC Hospital ( Site 0401)	Osaka
Japan	Medical Corporation Houeikai Sekino Clinical Pharmacology Clinic ( Site 0403)	Tokyo
Spain	Instituto de Ciencias Medicas - ICM ( Site 0300)	Alicante
Spain	CAP Centelles ( Site 0301)	Centelles
Spain	Hospital Universitario Quiron Madrid ( Site 0304)	Pozuelo de Alarcon	Madrid
Taiwan	National Taiwan University Hospital ( Site 0500)	Taipei
Taiwan	National Cheng Kung University Hospital ( Site 0501)	Taiwan
United States	Charlottesville Medical Research Center, LLC ( Site 1003)	Charlottesville	Virginia
United States	Rapid Medical Research, Inc. ( Site 1011)	Cleveland	Ohio
United States	Indago Research & Health Center, Inc ( Site 1002)	Hialeah	Florida
United States	Research Centers of America, LLC ( Site 1014)	Hollywood	Florida
United States	Wake Research Clinical Research Center of Nevada, LLC ( Site 1010)	Las Vegas	Nevada
United States	Synexus ( Site 1001)	Mesa	Arizona
United States	Advanced Medical Research Institute ( Site 0117)	Miami	Florida
United States	Lakes Research LLC ( Site 1005)	Miami Lakes	Florida
United States	Health Research of Hampton Roads, Inc. ( Site 1007)	Newport News	Virginia
United States	Alliance for Multispecialty Research, LLC ( Site 1008)	Newton	Kansas
United States	J Lewis Research Inc / Foothill Family Clinic ( Site 1013)	Salt Lake City	Utah
United States	Diagnostics Research Group ( Site 1000)	San Antonio	Texas
United States	Synexus ( Site 1009)	San Antonio	Texas
United States	Artemis Institute for Clinical Research ( Site 1012)	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

United States,  Canada,  Japan,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With a Solicited Injection-site Adverse Event	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. Solicited injection-site AEs consist of redness/erythema, swelling, and tenderness/pain.	Up to Day 5 postvaccination
Primary	Percentage of Participants With Solicited Systemic Adverse Events	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 Day 14 postvaccination
Primary	Percentage of Participants With a Vaccine-related Serious Adverse Event	A serious adverse event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is another important medical event. SAEs that are reported to be at least possibly related by the investigator to study vaccination will be summarized.	Up to Month 6
Primary	Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity at Day 30	Serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) (estimated) and GMT ratios with 95% CIs and 1-sided p-values 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) were determined using a multiplexed opsonophagocytic assay (MOPA). The measure type of "number" presented in the data table below for serotype-specific OPA titer is the geometric mean.	Day 30
Primary	Percentage of Participants With =4 Fold Rise in Serotype-specific OPA for 2 Unique V114 Serotypes	Activity for the serotypes contained in Prevnar 13™ and V114 was determined using a multiplexed opsonophagocytic assay (MOPA). The percentage of participants who had =4-fold rise in OPA titers were calculated from baseline (Day 1) to 30 days postvaccination (Day 30) for OPA responses for the 2 unique serotypes in V114. The observed response percentage (m/n) included: m=the number of participants with the indicated response divided by n=the number of participants contributing to the analysis. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the percentage point difference); within-group CIs were not calculated.	Day 1 (Baseline) and Day 30
Secondary	GMT of Serotype-specific OPA for Serotype 3 at Day 30	Serotype-specific OPA GMTs (estimated) and GMT ratios with 95% CIs and 1-sided p-values were calculated using a 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 serotype 3 contained in Prevnar 13™ and V114 was determined using a MOPA. The measure type of "number" presented in the data table below for serotype-specific OPA titer is the geometric mean.	Day 30
Secondary	Percentage of Participants With =4 Fold Rise in Serotype-specific OPA for Serotype 3 OPA Responses	Activity for serotype 3 contained in Prevnar 13™ and V114 was determined using a MOPA. The observed response percentage of participants (m/n) who had =4-fold rise in OPA titers were calculated from baseline to postvaccination. n=Number of participants contributing to the analysis; m=Number of participants with the indicated response. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the percentage point difference); within-group CIs were not calculated.	Day 1 (Baseline) and Day 30
Secondary	Geometric Mean Concentration of Serotype-specific IgG at Day 30	Serotype-specific Immunoglobulin G (IgG) geometric mean concentrations (GMCs) (estimated) and GMC ratios with 95% confidence intervals (CIs) and 1-sided p-values were calculated using a cLDA model utilizing data from both vaccination groups. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the GMC ratios); within-group CIs were not calculated. IgG 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 an electrochemiluminescence assay. The measure type of "number" presented in the data table below for serotype-specific IgG concentration is the geometric mean.	Day 30
Secondary	Geometric Mean Fold Rise in Serotype-specific OPA	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 defined as the geometric mean of the ratio of concentration at Day 30 after vaccination divided by concentration at baseline.	Day 1 (Baseline) and Day 30
Secondary	Geometric Mean Fold Rise in Serotype-specific IgG	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 an electrochemiluminescence assay. Geometric mean fold rise (GMFR) is defined as the geometric mean of the ratio of concentration at Day 30 after vaccination divided by concentration at baseline.	Day 1 (Baseline) and Day 30
Secondary	Percentage of Participants With =4-Fold Rise in Serotype-specific OPA Titer	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 Concentration	Activity 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 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