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)

Phase 3

Completed

Conditions: Pneumococcal Infections

Interventions: Biological: Prevnar 13™
Biological: Pneumovax™ 23
Biological: Placebo

Registration Number: NCT02225587

Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 400

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1: Prevnar 13™ → Pneumovax™ 23 → Placebo	Pneumovax™ 23	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.
Group 1: Prevnar 13™ → Pneumovax™ 23 → Placebo	Prevnar 13™	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.
Group 2: Prevnar 13™ → Placebo → Pneumovax™ 23	Prevnar 13™	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.
Group 1: Prevnar 13™ → Pneumovax™ 23 → Placebo	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.
Group 2: Prevnar 13™ → Placebo → Pneumovax™ 23	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.
Group 2: Prevnar 13™ → Placebo → Pneumovax™ 23	Placebo	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With an Injection-site Adverse Event	Up to 14 days after any vaccination (Up to 28 weeks)	An injection site adverse event (AE) includes the following AEs at the injection site: redness, swelling, and pain/tenderness.
Percentage of Participants With an Adverse Event (AE)	Up to 14 days after any vaccination (Up to 28 weeks)	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.
Percentage of Participants With a Systemic Adverse Event	Up to 14 days after any vaccination (Up to 28 weeks)	Systemic adverse events (AEs) include, but are not restricted to the following AE terms: muscle pain, joint pain, headache, and tiredness.
Percentage of Participants With a Serious Adverse Event (SAE)	Up to 30 weeks	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.
Percentage of Participants With a Vaccine-related Serious Adverse Event (SAE) or Vaccine-related Death	Up to 30 weeks	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.
Geometric Mean Titers to Pneumococcal Serotypes 22F and 33F at Week 12	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.
Percentage of Participants Who Discontinued Vaccination Due to an Adverse Event	Up to 26 weeks	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.
Geometric Mean Titers to Pneumococcal Serotypes 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F, at Week 12	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.

Secondary Outcome Measures

Name	Time	Method
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	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.
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	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.
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	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.