A Trial To Evaluate A Multivalent Pneumococcal Conjugate Vaccine In Healthy Adults 50-85 Years Of Age

Study Overview
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Brief Summary
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This is a 2-stage, phase 1/2, randomized, active-controlled, observer-blinded study with a 2-arm parallel design in each stage. In Stage 1 healthy adults 50 to 64 years of age with no history of pneumococcal vaccination will be randomized equally to receive either a single intramuscular dose of multivalent pneumococcal conjugate vaccine or a licensed tetanus, diphtheria, acellular pertussis combination vaccine (Tdap) (control group). In Stage 2 healthy adults 65 to 85 years of age previously vaccinated with Prevnar 13 >=2 months prior to investigational product administration will be randomized equally to receive either a single intramuscular dose of multivalent pneumococcal conjugate vaccine or the licensed 23-valent pneumococcal polysaccharide vaccine (control group).

Official Title
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A PHASE 1/2, RANDOMIZED, OBSERVER-BLINDED TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A MULTIVALENT PNEUMOCOCCAL CONJUGATE VACCINE IN HEALTHY ADULTS 50 THROUGH 85 YEARS OF AGE

Conditions
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Pneumococcal Infections

Intervention / Treatment
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* Biological: Multivalent
* Biological: Tdap
* Biological: polysaccharide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage 1: Healthy male or female adults 50 to 64 years of age with no history of pneumococcal vaccination Stage 2: Healthy male or female adults 65 to 85 years of age previously vaccinated with Prevnar 13 >= 2 months prior to investigational product administration Exclusion Criteria: Stage 1: Vaccination within 12 months before investigational product administration with diphtheria-, pertussis-, or tetanus-containing vaccine Stage 2: Previous vaccination with any pneumococcal vaccine other than a single prior dose of Prevnar 13

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stage 1 multivalent (ages 50-64 years)<br>multivalent | Biological: Multivalent<br>* Pneumococcal conjugate vaccine<br>|
| Active Comparator: Stage 1 Tdap (ages 50-64 years)<br>Tdap | Biological: Tdap<br>* Tetanus, diphtheria, acellular pertussis vaccine<br>|
| Experimental: Stage 2 multivalent (ages 65-85 years)<br>multivalent | Biological: Multivalent<br>* Pneumococcal conjugate vaccine<br>|
| Active Comparator: Stage 2 polysaccharide (ages 65-85 years)<br>polysaccharide | Biological: polysaccharide<br>* 23-valent pneumococcal polysaccharide vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage 1: Percentage of Participants With Local Reactions Within 14 Days After Vaccination | Local reactions included pain at injection site, swelling and redness recorded by participants in an electronic diary (e-diary). Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 centimeter (cm). Redness and swelling were graded as mild: greater than (>) 2.0 to 5.0 cm, moderate: >5.0 to 10.0 cm and severe: >10.0 cm. Pain at injection site was graded as mild: did not interfere with activity, moderate: interfered with activity and severe: prevented daily activity. | within 14 days after vaccination | 
| Stage 2: Percentage of Participants With Local Reactions Within 14 Days After Vaccination | Local reactions included pain at injection site, swelling and redness recorded by participants in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild: >2.0 to 5.0 cm, moderate: >5.0 to 10.0 cm and severe: >10.0 cm. Pain at injection site was graded as mild: did not interfere with activity, moderate: interfered with activity and severe: prevented daily activity. | within 14 days after vaccination | 
| Stage 1: Percentage of Participants With Systemic Events Within 14 Days After Vaccination | Systemic events included fever, fatigue, headache, muscle pain and joint pain recorded by participants in an e-diary. Fever was categorized as: >=38.0 degrees Celsius (C), >=38.0 to 38.4 degrees C, >38.4 to 38.9 degrees C, >38.9 to 40.0 degrees C and >40.0 degrees C. Fatigue, headache, muscle pain and joint pain were graded as any, mild: did not interfere with activity, moderate: some interference with activity and severe: prevented daily routine activity. | within 14 days after vaccination | 
| Stage 2: Percentage of Participants With Systemic Events Within 14 Days After Vaccination | Systemic events included fever, fatigue, headache, muscle pain and joint pain recorded by participants in an e-diary. Fever was categorized as: >=38.0 degrees C, >=38.0 to 38.4 degrees C, >38.4 to 38.9 degrees C, >38.9 to 40.0 degrees C and >40.0 degrees C. Fatigue, headache, muscle pain and joint pain were graded as any, mild: did not interfere with activity, moderate: some interference with activity and severe: prevented daily routine activity. | within 14 days after vaccination | 
| Stage 1: Percentage of Participants With Adverse Events (AEs) Within 1 Month After Vaccination | An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. AEs included both serious and non-serious adverse events. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both AEs and Non-SAEs. | within 1 month after vaccination | 
| Stage 2: Percentage of Participants With Adverse Events (AEs) Within 1 Month After Vaccination | An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. AEs included both serious and non-serious adverse events. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both AEs and Non-SAEs. | within 1 month after vaccination | 
| Stage 1: Percentage of Participants With Serious Adverse Events (SAEs) Within 6 Months After Vaccination | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | within 6 months after vaccination | 
| Stage 2: Percentage of Participants With Serious Adverse Events (SAEs) Within 6 Months After Vaccination | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | within 6 months after vaccination | 
| Stage 1: Percentage of Participants With Newly Diagnosed Chronic Medical Conditions (NDCMCs) Within 6 Months After Vaccination | An NDCMC was defined as a disease or medical condition, not previously identified, that is expected to be persistent or is otherwise long-lasting in its effects. | within 6 months after vaccination | 
| Stage 2: Percentage of Participants With Newly Diagnosed Chronic Medical Conditions (NDCMCs) Within 6 Months After Vaccination | An NDCMC was defined as a disease or medical condition, not previously identified, that is expected to be persistent or is otherwise long-lasting in its effects. | within 6 months after vaccination | 
| Stage 2: Percentage of Participants With Serious Adverse Events (SAEs) Within 12 Months After Vaccination | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | within 12 months after vaccination | 
| Stage 2: Percentage of Participants With Newly Diagnosed Chronic Medical Conditions (NDCMCs) Within 12 Months After Vaccination | An NDCMC was defined as a disease or medical condition, not previously identified, that is expected to be persistent or is otherwise long-lasting in its effects. | within 12 months after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage 1: Serotype-specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titer (GMT) 1 Month After Vaccination | Antibody-mediated serum OPA against the 7 pneumococcal serotypes specific to c7vPnC (serotypes 8, 10A, 11A, 12F, 15B, 22F and 33F) were measured using a pneumococcal OPA assay. Results were expressed as OPA GMTs. Assay results below the lower limit of quantitation (LLOQ) were set to 0.5*LLOQ in the analysis. Evaluable immunogenicity population = EIP. | 1 month after vaccination | 
| Stage 2: Serotype-specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titer (GMT) 1 Month After Vaccination | Antibody-mediated serum OPA against the 7 common pneumococcal serotypes specific to c7vPnC (serotypes 8, 10A, 11A, 12F, 15B, 22F and 33F) were measured using a pneumococcal OPA assay. Results were expressed as OPA GMTs. Assay results below the LLOQ were set to 0.5*LLOQ in the analysis. | within 1 month after vaccination | 
| Stage 1: Serotype-specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Fold Rises (GMFRs) From Pre-vaccination to 1 Month After Vaccination | GMFR for the 7 pneumococcal serotypes (serotypes 8, 10A, 11A, 12F, 15B, 22F and 33F) from before Vaccination to one month after Vaccination. Assay results below the LLOQ were set to 0.5*LLOQ in the analysis. | before Vaccination to 1 month after Vaccination | 
| Stage 2: Serotype-specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Fold Rises (GMFRs) From Pre-Vaccination to 1 Month After Vaccination | GMFR for the 7 pneumococcal serotypes (serotypes 8, 10A, 11A, 12F, 15B, 22F and 33F) from before Vaccination to one month after Vaccination. Assay results below the LLOQ were set to 0.5*LLOQ in the analysis. | before Vaccination to 1 month after Vaccination |