Vaccine Information: VAXNEUVANCE (Page 3 of 4)

14.2 Clinical Trials in Pneumococcal Vaccine-Naïve Adults

Study 1

Study 1 assessed serotype-specific opsonophagocytic activity (OPA) responses for each of the 15 serotypes contained in VAXNEUVANCE at 30 days postvaccination in a double-blind, active comparator-controlled study that enrolled pneumococcal vaccine-naïve participants 50 years of age and older. Participants were randomized to receive either VAXNEUVANCE (N=604) or Prevnar 13 (N=601) at sites in USA, Canada, Spain, Taiwan, and Japan. The mean age of participants was 66 years and 57.3% were female. The racial distribution was as follows: 67.7% were White, 25.1% were Asian, 6.1% were Black or African American and 22.0% were of Hispanic or Latino ethnicity.

Table 12 summarizes the OPA geometric mean antibody titers (GMTs) at 30 days postvaccination for the 15 serotypes contained in VAXNEUVANCE. The study demonstrated that VAXNEUVANCE is noninferior to Prevnar 13 for the 13 shared serotypes and induces statistically significantly greater OPA GMTs compared to Prevnar 13 for shared serotype 3 and for the 2 unique serotypes (22F, 33F).

Table 12: Serotype-Specific OPA GMTs in Pneumococcal Vaccine-Naïve Adults 50 Years of Age and Older (Study 1)

PneumococcalSerotype	VAXNEUVANCE(N = 602)		Prevnar 13(N = 600)		GMT Ratio *(VAXNEUVANCE/Prevnar 13)(95% CI)*
	n	GMT *	n	GMT *
N=Number of participants randomized and vaccinated; n=Number of participants contributing to the analysis that had at least one pre-dose OPA measurement (VAXNEUVANCE, n=537-597; Prevnar 13, n=545-595) or post-dose OPA measurement (VAXNEUVANCE, n=568-580; Prevnar 13, n=528-574).CI=confidence interval; cLDA=constrained longitudinal data analysis; GMT=geometric mean titer; OPA=opsonophagocytic activity.
* GMTs, GMT ratio, and 95% CI are estimated from a cLDA model. † Non-inferiority for the 13 shared serotypes was met if the lower bound of the 95% CI for the GMT ratio (VAXNEUVANCE/Prevnar 13) was > 0.5. ‡ Statistically significantly greater OPA GMT for serotype 3 was based on the lower bound of the 95% CI for the estimated GMT ratio (VAXNEUVANCE/Prevnar 13) > 1.2. § Statistically significantly greater OPA GMTs for serotypes 22F and 33F was based on the lower bound of the 95% CI for the estimated GMT ratio (VAXNEUVANCE/Prevnar 13) > 2.0.
Serotype †
1	598	257	598	321	0.80 (0.66, 0.97)
3‡	598	215	598	133	1.62 (1.40, 1.87)
4	598	1109	598	1633	0.68 (0.57, 0.80)
5	598	445	598	560	0.79 (0.64, 0.98)
6A	596	5371	596	5276	1.02 (0.85, 1.22)
6B	598	3984	598	3179	1.25 (1.04, 1.51)
7F	596	4575	596	5830	0.78 (0.68, 0.90)
9V	598	1809	597	2193	0.83 (0.71, 0.96)
14	598	1976	598	2619	0.75 (0.64, 0.89)
18C	598	2749	598	2552	1.08 (0.91, 1.27)
19A	598	3177	597	3921	0.81 (0.70, 0.94)
19F	598	1688	598	1884	0.90 (0.77, 1.04)
23F	598	2029	598	1723	1.18 (0.96, 1.44)
Additional Serotypes §
22F	594	2381	585	73	32.52 (25.87, 40.88)
33F	598	8010	597	1114	7.19 (6.13, 8.43)

Study 3

In a double-blind, active comparator-controlled, descriptive study (Study 3), pneumococcal vaccine-naïve adults 50 years of age and older were randomized to receive either VAXNEUVANCE (N=327) or Prevnar 13 (N=325), followed by PNEUMOVAX 23 one year later.

Following vaccination with PNEUMOVAX 23, OPA GMTs were numerically similar between the two vaccination groups for the 15 serotypes in VAXNEUVANCE.

Study 4

In a double-blind, descriptive study (Study 4), adults 18 through 49 years of age, including individuals with increased risk of developing pneumococcal disease, were randomized to receive VAXNEUVANCE (N=1,135) or Prevnar 13 (N=380), followed by PNEUMOVAX 23 six months later [see Adverse Reactions (6.1)]. Among those who received VAXNEUVANCE, 620 participants had one risk factor and 228 participants had two or more risk factors for pneumococcal disease.

Table 13 presents OPA GMTs in the overall study population for each of the 15 serotypes 30 days following vaccination with VAXNEUVANCE or Prevnar 13.

Table 13: Serotype-Specific OPA GMTs in Pneumococcal Vaccine-Naïve Adults 18 through 49 Years of Age With or Without Risk Factors for Pneumococcal Disease (Study 4)

PneumococcalSerotype	VAXNEUVANCE(N = 1,133)			Prevnar 13(N = 379)
	n	Observed GMT	95% CI *	n	Observed GMT	95% CI *
N=Number of participants randomized and vaccinated; n=Number of participants contributing to the analysis. CI=confidence interval; GMT=geometric mean titer; OPA=opsonophagocytic activity.
* The within-group 95% CIs are obtained by exponentiating the CIs of the mean of the natural log values based on the t-distribution.
Serotype
1	1004	267	(242, 295)	337	267	(220, 324)
3	990	198	(184, 214)	336	150	(129, 173)
4	1001	1401	(1294, 1517)	338	2568	(2268, 2908)
5	1003	560	(508, 618)	339	731	(613, 873)
6A	994	12763	(11772, 13838)	333	11313	(9739, 13141)
6B	999	10164	(9486, 10891)	338	6958	(5987, 8086)
7F	1004	5725	(5382, 6090)	338	7583	(6762, 8503)
9V	1000	3353	(3132, 3590)	339	3969	(3541, 4449)
14	1001	5245	(4860, 5660)	339	5863	(5191, 6623)
18C	999	5695	(5314, 6103)	339	3050	(2685, 3465)
19A	1001	5335	(4985, 5710)	339	5884	(5221, 6632)
19F	1003	3253	(3051, 3468)	339	3272	(2949, 3631)
23F	1001	4828	(4443, 5247)	337	3876	(3323, 4521)
Additional Serotypes
22F	991	3939	(3654, 4246)	317	291	(221, 383)
33F	999	11734	(10917, 12612)	334	2181	(1826, 2606)

Following vaccination with PNEUMOVAX 23, the OPA GMTs for the 15 serotypes in VAXNEUVANCE were numerically similar among subjects who had received VAXNEUVANCE or Prevnar 13 for the first vaccination.