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)

Study Overview
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Brief Summary
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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.

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

Conditions
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Pneumococcal Infections

Intervention / Treatment
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* Biological: Prevnar 13™
* Biological: Pneumovax™ 23
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Prevnar 13™ → Pneumovax™ 23 → Placebo<br>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™<br>* 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.<br>Biological: Pneumovax™ 23<br>* 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.<br>Biological: Placebo<br>* Injections are to be administered into the deltoid muscle of the upper arm.<br>|
| Placebo Comparator: Group 2: Prevnar 13™ → Placebo → Pneumovax™ 23<br>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™<br>* 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.<br>Biological: Pneumovax™ 23<br>* 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.<br>Biological: Placebo<br>* Injections are to be administered into the deltoid muscle of the upper arm.<br>|

What is the study measuring?
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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 |