Evaluation of the Safety and Immunogenicity of Sequential Administration of Prevnar 13™ and Pneumovax™ 23 in Healthy Participants 50 Years of Age and Older (V110-029)

Sequential Administration of Prevnar 13™ and Pneumovax™ 23 in Healthy Subjects 50 Years of Age and Older

The purpose of this study is to evaluate the safety and immunogenicity of sequential administration of Prevnar 13™ and Pneumovax™ 23 in healthy participants 50 years of age and older. The primary hypotheses in the study are that 1) geometric mean titers (GMTs) to pneumococcal serotypes 22F and 33F (serotypes in Pneumovax™ 23 but not in Prevnar 13™) as measured at Week 12 are superior in participants administered Prevnar 13™ on Day 1 and Pneumovax™ 23 at Week 8, as compared with participants administered Prevnar 13™ on Day 1 and placebo at Week 8 and 2) GMTs to pneumococcal serotypes shared by the two vaccines as measured at Week 12 are non-inferior in participants administered Prevnar 13™ followed by Pneumovax™ 23 as compared with participants administered Prevnar 13™ followed by placebo.

Study Overview

• Status: Completed
• Conditions: Pneumococcal Infections
• Intervention / Treatment: Biological: Prevnar 13™; Biological: Pneumovax™ 23; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 400
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Any chronic illness must be documented to be in stable condition
• Male, or a female agrees to remain abstinent, or use, or have their partner use, 2 acceptable methods of contraception through 6 weeks after receiving study vaccination; or a female who is not of reproductive potential

Exclusion Criteria:

• Is or has an immediate family member who is investigational site or sponsor staff directly involved with this trial
• Prior administration of any pneumococcal vaccine
• History of invasive pneumococcal disease
• Known hypersensitivity to any component of the pneumococcal polysaccharide vaccine, of the pneumococcal conjugate vaccine, or any diphtheria toxoid-containing vaccine
• Known or suspected impairment of immunological function, documented Human Immunodeficiency Virus (HIV) infection, asplenia, or history of autoimmune disease
• Received systemic corticosteroids (equivalent of >=2 mg/kg total daily dose of prednisone or >=20 mg/kg for persons weighing >10 kg) for >=14 consecutive days and has not completed treatment <=30 days before study vaccination, or has received systemic corticosteroids exceeding physiological doses (~5 mg/day prednisone equivalent) within 14 days before study vaccination (topical, ophthalmic, intra-articular, and inhaled/nebulized steroids are permitted).
• Has a coagulation disorder contraindicating intramuscular vaccination
• Receiving immunosuppressive therapy, including chemotherapeutic agents used to treat cancer or other conditions, and treatments associated with organ or bone marrow transplantation or autoimmune disease
• Received a blood transfusion or blood products, including immunoglobulins <=6 months before receiving study vaccine, or is scheduled to receive them within 30 days
• Participated in another clinical study of an investigational product <=2 months before or during the current study
• Is breast-feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Prevnar 13™ → Pneumovax™ 23 → Placebo; Prevnar 13™ 0.5 mL intramuscular injection on Day 1, Pneumovax™ 23 0.5 mL intramuscular injection at Week 8, and Placebo 0.5 mL intramuscular injection at Week 26. Injections are to be administered in alternating limbs, if possible.	Biological: Prevnar 13™; Pneumococcal vaccine containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. Injections are to be administered into the deltoid muscle of the upper arm.; Biological: Pneumovax™ 23; Pneumococcal vaccine containing serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F. Injections are to be administered into the deltoid muscle of the upper arm.; Biological: Placebo; Injections are to be administered into the deltoid muscle of the upper arm.
Placebo Comparator: Group 2: Prevnar 13™ → Placebo → Pneumovax™ 23; Prevnar 13™ 0.5 mL intramuscular injection on Day 1, Placebo 0.5 mL intramuscular injection at Week 8, and Pneumovax™ 23 0.5 mL intramuscular injection at Week 26. Injections are to be administered in alternating limbs, if possible.	Biological: Prevnar 13™; Pneumococcal vaccine containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. Injections are to be administered into the deltoid muscle of the upper arm.; Biological: Pneumovax™ 23; Pneumococcal vaccine containing serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F. Injections are to be administered into the deltoid muscle of the upper arm.; Biological: Placebo; Injections are to be administered into the deltoid muscle of the upper arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With an Adverse Event (AE)	An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.	Up to 14 days after any vaccination (Up to 28 weeks)
Percentage of Participants With an Injection-site Adverse Event	An injection site adverse event (AE) includes the following AEs at the injection site: redness, swelling, and pain/tenderness.	Up to 14 days after any vaccination (Up to 28 weeks)
Percentage of Participants With a Systemic Adverse Event	Systemic adverse events (AEs) include, but are not restricted to the following AE terms: muscle pain, joint pain, headache, and tiredness.	Up to 14 days after any vaccination (Up to 28 weeks)
Percentage of Participants With a Serious Adverse Event (SAE)	A serious adverse event (SAE) is any adverse event occurring at any dose or during any use of Sponsor's product that: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is another important medical event; is a cancer; or is associated with an overdose.	Up to 30 weeks
Percentage of Participants With a Vaccine-related Serious Adverse Event (SAE) or Vaccine-related Death	A serious adverse event (SAE) is any adverse event occurring at any dose or during any use of Sponsor's product that: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is another important medical event; is a cancer; or is associated with an overdose. The investigator determined whether the SAE or death was related to vaccine treatment.	Up to 30 weeks
Percentage of Participants Who Discontinued Vaccination Due to an Adverse Event	An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.	Up to 26 weeks
Geometric Mean Titers to Pneumococcal Serotypes 22F and 33F at Week 12	Vaccine-induced functional antibodies to serotypes 22F and 33F, which are unique to PNEUMOVAX™ 23, were measured by the multiplex opsonophagocytic activity 4 (MOPA-4) assay, which is based on the ability of antibody in the serum to initiate killing of bacterial pneumococci.	Week 12
Geometric Mean Titers to Pneumococcal Serotypes 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F, at Week 12	Vaccine-induced functional antibodies to serotypes 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F, which are contained in both Prevnar 13™ and PNEUMOVAX™ 23, were measured by the MOPA-4 assay, which is based on the ability of antibody in the serum to initiate killing of bacterial pneumococci.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers to Pneumococcal Serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F at Week 8	Vaccine-induced functional antibodies were measured by the MOPA-4 assay, which is based on the ability of antibody in the serum to initiate killing of bacterial pneumococci.	Week 8
Geometric Mean Titers to Pneumococcal Serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F at Week 26	Vaccine-induced functional antibodies were measured by the MOPA-4 assay, which is based on the ability of antibody in the serum to initiate killing of bacterial pneumococci.	Week 26
Geometric Mean Titers to Pneumococcal Serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F at Week 30	Vaccine-induced functional antibodies were measured by the MOPA-4 assay, which is based on the ability of antibody in the serum to initiate killing of bacterial pneumococci.	Week 30

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Buchwald UK, Andrews CP, Ervin J, Peterson JT, Tamms GM, Krupa D, Ajiboye P, Roalfe L, Krick AL, Sterling TM, Wang M, Martin JC, Stek JE, Kohn MA, Folaranmi T, Abeygunawardana C, Hartzel J, Musey LK; V110-029 Study Group. Sequential administration of Prevnar 13 and PNEUMOVAX 23 in healthy participants 50 years of age and older. Hum Vaccin Immunother. 2021 Aug 3;17(8):2678-2690. doi: 10.1080/21645515.2021.1888621. Epub 2021 May 21.

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2014
• Primary Completion (Actual): July 6, 2015
• Study Completion (Actual): July 6, 2015

Study Registration Dates

• First Submitted: August 22, 2014
• First Submitted That Met QC Criteria: August 22, 2014
• First Posted (Estimate): August 26, 2014

Study Record Updates

• Last Update Posted (Actual): November 2, 2021
• Last Update Submitted That Met QC Criteria: October 25, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: V110-029 (Other Identifier: Merck); 2013-003027-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No