Safety, Tolerability, and Immunogenicity of Two Formulations of V114 in Healthy Adults 50 Years of Age or Older (V114-006)

A Multicenter, Double-Blind Study of the Safety, Tolerability, and Immunogenicity of V114 Compared to Prevnar 13™ in Healthy Pneumococcal Vaccine-Naïve Adults 50 Years of Age or Older

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02547649

Enrollment

690

Registered

2015-09-11

Start date

2015-10-08

Completion date

2016-01-20

Last updated

2019-04-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pneumococcal Infections

Brief summary

The purpose of this study is to assess the safety, tolerability, and immunogenicity of a single dose of different formulations of V114 (V114-A and V114-B) and Prevnar 13® (pneumococcal 13-valent conjugate vaccine) in adult participants ≥50 years of age in good health.

Interventions

BIOLOGICALV114-A

Formulation A of V114 contains 2 µg of pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, and 33F; 4 µg of serotype 6B; 32 µg of CRM197 protein carrier; and 125 µg of Aluminum Phosphate Adjuvant in each 0.5 mL dose (V114-A uses a unique excipient to improve stability of the vaccine against physical stress).

BIOLOGICALV114-B

Formulation B of V114 contains 2 µg of pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, and 33F; 4 µg of serotype 6B; 32 µg of CRM197 protein carrier; and 125 µg of Aluminum Phosphate Adjuvant in each 0.5 mL dose (V114-B uses a unique excipient to improve stability of the vaccine against physical stress).

BIOLOGICALPrevnar 13®

Pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 mcg each), and 6B (4.4 mcg) in each 0.5 mL dose.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

50 Years to No maximum

Healthy volunteers

Yes

Inclusion criteria

* Good health; any underlying chronic illness must be documented to be in stable condition * Highly unlikely to conceive through 6 weeks after administration of the study vaccine

Exclusion criteria

* Prior administration of any pneumococcal vaccine * History of invasive pneumococcal disease (IPD) \[positive blood culture, positive cerebrospinal fluid culture, or other sterile site) or known history of other culture-positive pneumococcal disease * Known hypersensitivity to any vaccine component * Known or suspected impairment of immune function * Received systemic corticosteroids for \>=14 consecutive days and has not completed treatment \<=30 days prior to study entry, or received systemic corticosteroids exceeding physiologic replacement doses within 14 days prior to study vaccination * Coagulation disorder contraindicating intramuscular vaccination * Receives 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 within the 6 months before receipt of study vaccine or is scheduled to receive a blood transfusion or blood product within 30 days of receipt of study vaccine. Autologous blood transfusions are not considered an exclusion criterion. * Participated in another clinical study of an investigational product within 2 months before the beginning of or any time during the duration of the current clinical study * Breast feeding * User of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence

Design outcomes

Primary

Measure	Time frame	Description
Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	Day 30 (one month after vaccination)	The OPA GMTs of each common serotype (CS) and V114-specific serotype (VS) were determined in each arm. Titer levels were determined with the multiplexed opsonophagocytic assay (MOPA).
Percentage of Participants With a Solicited Systemic Adverse Event (AE)	Up to 14 days after vaccination	The percentage of participants experiencing ≥1 solicited systemic AE(s) in each arm was determined.
Percentage of Participants With a Serious Adverse Event (SAE)	Up to 30 days after vaccination	The percentage of participants experiencing ≥1 SAE(s) in each arm was determined.
Percentage of Participants With Vaccine-Related Serious Adverse Event (SAE)	Up to 30 days after vaccination	The percentage of participants experiencing ≥1 vaccine-related SAEs(s) in each arm was determined.
Percentage of Participants With an Adverse Event (AE)	Up to 14 days after vaccination	The percentage of participants experiencing ≥1 AE(s) in each arm was determined. An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Percentage of Participants With a Solicited Injection-site Adverse Event (AE)	Up to 14 days after vaccination	The percentage of participants experiencing ≥1 solicited injection-site AE(s) in each arm was determined.

Secondary

Measure	Time frame	Description
Percentage of Participants With a ≥4-fold Rise From Baseline in Serotype-specific Opsonophagocytic Killing Activity (OPA) Geometric Mean Titers (GMTs)	Baseline and Day 30 (one month after vaccination)	The percentage of participants with ≥4-fold rise from baseline in OPA GMTs of each common serotype (CS) and V114-specific serotype (VS) were compared in the V114 and Prevnar® 13 arms. Estimated GMT, GMT ratio, 95% CI, and p-values were obtained from a constrained longitudinal data analysis (cLDA) model.
Percentage of Participants With a ≥4-fold Rise From Baseline in Geometric Mean Concentrations (GMCs) of Serotype-specific Immunoglobulin G (IgG) Antibodies	Baseline and Day 30 (one month after vaccination)	The percentage of participants with ≥4-fold rise from baseline in IgG GMCs of each common serotype (CS) and V114-specific serotype (VS) were compared in the V114 and Prevnar® 13 arms. Estimated GMT, GMT ratio, 95% CI, and p-values were obtained from a constrained longitudinal data analysis (cLDA) model.
Geometric Mean Concentrations (GMCs) of Serotype-specific Immunoglobulin G (IgG) at One Month Post-Vaccination	Day 30 (one month after vaccination)	The IgG GMCs of each common pneumococcal serotype (CS) and V114-specific pneumococcal serotype (VS) were determined for each arm. Concentrations were determined with pneumococcal electrochemiluminescence (PnECL).

Participant flow

Recruitment details

Healthy, pneumococcal vaccine-naïve adults ≥50 years of age were recruited at 23 sites in the United States.

Participants by arm

Arm	Count
V114-A Participants receive a single 0.5 mL intramuscular injection of V114 Formulation A on Day 1. Formulation A of V114 contains 2 µg of pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, and 33F; 4 µg of serotype 6B; 32 µg of CRM197 protein carrier; and 125 µg of Aluminum Phosphate Adjuvant in each 0.5 mL dose (V114-A uses a unique excipient to improve stability of the vaccine against physical stress).	231
V114-B Participants receive a single 0.5 mL intramuscular injection of V114 Formulation B on Day 1. Formulation B of V114 contains 2 µg of pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, and 33F; 4 µg of serotype 6B; 32 µg of CRM197 protein carrier; and 125 µg of Aluminum Phosphate Adjuvant in each 0.5 mL dose (V114-B uses a unique excipient to improve stability of the vaccine against physical stress).	231
Prevnar 13® Participants receive a single 0.5 mL intramuscular injection of Prevnar 13™ on Day 1.	227
Total	689

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Lost to Follow-up	3	1	1
Overall Study	Not vaccinated	0	0	1
Overall Study	Withdrawal by Subject	0	4	2

Baseline characteristics

Characteristic	V114-A	V114-B	Prevnar 13®	Total
Age, Continuous	63.4 Years STANDARD_DEVIATION 8.3	63.4 Years STANDARD_DEVIATION 8.3	63.1 Years STANDARD_DEVIATION 8.1	63.3 Years STANDARD_DEVIATION 8.2
Sex: Female, Male Female	126 Participants	126 Participants	133 Participants	385 Participants
Sex: Female, Male Male	105 Participants	105 Participants	94 Participants	304 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 231	0 / 231	0 / 227
other Total, other adverse events	169 / 231	163 / 231	148 / 227
serious Total, serious adverse events	1 / 231	2 / 231	0 / 227

Outcome results

Primary

Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination

The OPA GMTs of each common serotype (CS) and V114-specific serotype (VS) were determined in each arm. Titer levels were determined with the multiplexed opsonophagocytic assay (MOPA).

Time frame: Day 30 (one month after vaccination)

Population: All vaccinated participants with data available are included.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
V114-A	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS6B	4552.54 Titers
V114-A	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS19F	799.86 Titers
V114-A	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	VS22F	4743.78 Titers
V114-A	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS7F	2672.91 Titers
V114-A	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS4	1314.31 Titers
V114-A	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS23F	1233.60 Titers
V114-A	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS9V	2514.21 Titers
V114-A	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS3	104.78 Titers
V114-A	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS19A	1910.75 Titers
V114-A	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS5	273.79 Titers
V114-A	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS1	196.79 Titers
V114-A	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS18C	1896.14 Titers
V114-A	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS6A	3849.02 Titers
V114-A	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	VS33F	12457.52 Titers
V114-A	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS14	3496.71 Titers
V114-B	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS5	269.14 Titers
V114-B	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS1	144.01 Titers
V114-B	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS3	61.41 Titers
V114-B	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS4	929.53 Titers
V114-B	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS6A	4690.40 Titers
V114-B	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS6B	5082.56 Titers
V114-B	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS7F	2845.64 Titers
V114-B	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS9V	1962.09 Titers
V114-B	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS23F	2198.15 Titers
V114-B	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	VS22F	3976.66 Titers
V114-B	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS14	2664.63 Titers
V114-B	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS18C	2687.10 Titers
V114-B	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS19A	2477.75 Titers
V114-B	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS19F	1084.99 Titers
V114-B	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	VS33F	12614.22 Titers
Prevnar 13®	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS19F	810.05 Titers
Prevnar 13®	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS14	3111.50 Titers
Prevnar 13®	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS5	283.83 Titers
Prevnar 13®	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	VS22F	68.47 Titers
Prevnar 13®	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS18C	1528.79 Titers
Prevnar 13®	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS4	1195.73 Titers
Prevnar 13®	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS1	127.19 Titers
Prevnar 13®	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS19A	2045.57 Titers
Prevnar 13®	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS7F	3659.86 Titers
Prevnar 13®	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS3	33.10 Titers
Prevnar 13®	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS23F	1561.04 Titers
Prevnar 13®	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS6B	3909.05 Titers
Prevnar 13®	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	VS33F	2111.66 Titers
Prevnar 13®	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS9V	2112.91 Titers
Prevnar 13®	Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination	CS6A	4932.72 Titers

Primary

Percentage of Participants With an Adverse Event (AE)

The percentage of participants experiencing ≥1 AE(s) in each arm was determined. An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Time frame: Up to 14 days after vaccination