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

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

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

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Essink B, Peterson J, Yacisin K, Lal H, Mirza S, Xu X, Scully IL, Scott DA, Gruber WC, Jansen KU, Watson W. A randomized phase 1/2 study of the safety and immunogenicity of a multivalent pneumococcal conjugate vaccine in healthy adults 50 through 85 years of age. Hum Vaccin Immunother. 2021 Aug 3;17(8):2691-2699. doi: 10.1080/21645515.2021.1890511. Epub 2021 Mar 4.