Vaccine Information: PREVNAR 13 (Page 7 of 8)

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Modified double-blind means that the site staff dispensing and administering the vaccine were unblinded, but all other study personnel including the principal investigator and subject were blinded.

Clinical Trials Conducted in PPSV23 Previously Vaccinated Adults

In a Phase 3 active-controlled, modified double-blind clinical trial⁷ (Study 7) of Prevnar 13 in the US and Sweden, PPSV23 previously vaccinated adults aged ≥70 years who had received one dose of PPSV23 ≥5 years prior were randomly assigned (1:1) to receive either Prevnar 13 or PPSV23.

The mcOPA antibody GMTs elicited by Prevnar 13 were noninferior to those elicited by PPSV23 for the 12 serotypes in common, when Prevnar 13 or PPSV23 were administered at a minimum of 5 years after a prior dose of PPSV23. In addition, the lower limit of the 95% confidence interval for the mcOPA antibody GMT ratio (Prevnar 13/PPSV23) was greater than 1 for 9 of the serotypes in common.

For serotype 6A, which is unique to Prevnar 13, the proportion of subjects with a ≥4-fold increase in mcOPA antibody titers after Prevnar 13 (71.1%) was statistically significantly greater than after PPSV23 (27.3%) in PPSV23 previously vaccinated adults aged ≥70 years. mcOPA antibody GMTs for serotype 6A were statistically significantly greater after Prevnar 13 compared with after PPSV23.

This clinical trial demonstrated that in adults aged ≥70 years and previously vaccinated with PPSV23 ≥5 years prior, vaccination with Prevnar 13 elicited noninferior immune responses as compared with re-vaccination with PPSV23 (see Table 26).

Table 26: mcOPA Antibody GMTs in PPSV23-Previously Vaccinated Adults Aged ≥70 Years Given Prevnar 13 or PPSV23 (Study 7)*^, †^, ‡^, §^, ¶^, #

Serotype	Prevnar 13 N=400–426	PPSV23 N=395–445	Prevnar 13 Relative to PPSV23
	GMT	GMT	GMT Ratio	(95% CI)
GMT, Geometric Mean Titer.
* Study conducted in US and Sweden NCT00546572 (Study 7). † For the 12 common serotypes, noninferiority was defined as the lower limit of the 2-sided 95% CI for GMT ratio (Prevnar 13/PPSV23) greater than 0.5. ‡ For serotype 6A, which is unique to Prevnar 13, a statistically significantly greater response was defined as the lower limit of the 2-sided 95% CI for the GMT ratio (Prevnar 13/PPSV23) greater than 2. § mcOPA antibody for the 11 serotypes unique to PPSV23 but not contained in Prevnar 13 were not measured. ¶ Individual mcOPA antibody assay values below the assay LLOQ (lower limit of quantitation) were set at 0.50*LLOQ for the purpose of calculating the mcOPA antibody GMT. # Evaluable Immunogenicity Population. Þ 6A is a serotype unique to Prevnar 13 but not contained in PPSV23.
1	93	66	1.4	(1.14, 1.72)
3	59	53	1.1	(0.92, 1.31)
4	613	263	2.3	(1.76, 3.10)
5	100	61	1.6	(1.35, 2.00)
6A Þ	1056	160	6.6	(5.14, 8.49)
6B	1450	565	2.6	(2.00, 3.29)
7F	559	481	1.2	(0.97, 1.39)
9V	622	491	1.3	(1.08, 1.49)
14	355	366	1.0	(0.76, 1.23)
18C	972	573	1.7	(1.33, 2.16)
19A	366	216	1.7	(1.40, 2.07)
19F	422	295	1.4	(1.16, 1.77)
23F	177	53	3.3	(2.49, 4.47)

Clinical Trial of Sequential Vaccination of Prevnar 13 and PPSV23 in PPSV23 Unvaccinated Adults

In a randomized clinical trial conducted in PPSV23-unvaccinated adults 60 through 64 years of age⁸ (Study 8), 223 subjects received PPSV23 followed by Prevnar 13 one year later (PPSV23/Prevnar 13), and 478 received only Prevnar 13. mcOPA antibody titers were measured 1 month after vaccination with Prevnar 13 and are shown in Table 26. mcOPA antibody GMTs in those that received Prevnar 13 one year after PPSV23 were diminished when compared to those who received Prevnar 13 alone. Similarly, in exploratory analyses in PPSV23 previously vaccinated adults ≥70 years of age in Study 7, diminished mcOPA antibody GMTs were observed in those that received Prevnar 13 one year after PPSV23 when compared to those who received Prevnar 13 alone.

Table 27: mcOPA Antibody GMTs for the Prevnar 13 Serotypes in PPSV23 Unvaccinated Adults Aged 60 Through 64 Years Given Prevnar 13 Alone or Prevnar 13 One Year After PPSV23 (Study 8) (PPSV23/Prevnar 13)*^, †^, ‡^, §

	Prevnar 13 N=410–457		PPSV23/Prevnar 13 N=180–196
Serotype	GMT	(95% CI)	GMT	(95% CI)
GMT =Geometric Mean Titer.
* Study conducted in US NCT00574548 (Study 8). † Evaluable Immunogenicity Population. ‡ mcOPA antibody for the 11 serotypes unique to PPSV23 but not contained in Prevnar 13 were not measured. § Individual mcOPA antibody assay values below the assay LLOQ (lower limit of quantitation) were set at 0.50*LLOQ for the purpose of calculating the mcOPA antibody GMT. ¶ 6A is a serotype unique to Prevnar 13 but not contained in PPSV23.
1	219	(191, 252)	88	(72, 109)
3	78	(69, 88)	54	(45, 65)
4	2590	(2257, 2973)	988	(802, 1218)
5	258	(218, 305)	112	(90, 139)
6A ¶	2947	(2536, 3426)	1210	(962, 1522)
6B	2165	(1845, 2540)	832	(654, 1059)
7F	1518	(1339, 1721)	407	(342, 485)
9V	1279	(1142, 1432)	495	(426, 575)
14	790	(663, 941)	515	(402, 659)
18C	1683	(1437, 1971)	650	(504, 839)
19A	717	(629, 818)	299	(248, 361)
19F	812	(702, 939)	360	(293, 442)
23F	384	(312, 472)	142	(104, 193)

Also in Study 8, 266 subjects received Prevnar 13 followed by PPSV23 one year later (Prevnar 13/PPSV23). mcOPA antibody GMTs following PPSV23 administered one year after Prevnar 13 (Prevnar 13/PPSV23) were noninferior to those following a single dose of PPSV23 (N=237) for the 12 common serotypes [the lower limit of the 95% CI for the GMT ratio [Prevnar 13/PPSV23 relative to PPSV23] was >0.5] (see Table 27). In Study 6, which was conducted in PPSV23-unvaccinated adults 60 through 64 years of age, 108 subjects received PPSV23 3.5 to 4 years after Prevnar 13 (Prevnar 13/PPSV23) and 414 received a single dose of PPSV23. Higher serotype-specific mcOPA antibody GMT ratios [(Prevnar 13/PPSV23) / PPSV23] were generally observed compared to the one year dosing interval in Study 8.

Table 28: mcOPA Antibody GMTs for the Prevnar 13 Serotypes in PPSV23-Unvaccinated Adults Aged 60 Through 64 Years Given PPSV23 One Year After Prevnar 13 Relative to PPSV23 Alone (Study 8)*^, †^, ‡^, §

	Prevnar 13/PPSV23 N=216–233		PPSV23 N=214–229		GMT Ratio (Prevnar 13/PPSV23) / PPSV23
Serotype	GMT	95% CI	GMT	95% CI	Ratio	95% CI
GMT =Geometric Mean Titer.
* Study conducted in US NCT00574548 (Study 8). † Evaluable Immunogenicity Population. ‡ mcOPA antibody for the 11 serotypes unique to PPSV23 but not contained in Prevnar 13 were not measured. § Individual mcOPA antibody assay values below the assay LLOQ (lower limit of quantitation) were set at 0.50*LLOQ for the purpose of calculating the mcOPA antibody GMT. ¶ 6A is a serotype unique to Prevnar 13 but not contained in PPSV23. Anti-6A mcOPA antibody GMTs were descriptive in nature.
1	155	(131, 182)	161	(131, 198)	1.0	(0.74, 1.25)
3	127	(111, 145)	83	(71, 98)	1.5	(1.23, 1.87)
4	1409	(1202, 1651)	1468	(1139, 1893)	1.0	(0.71, 1.29)
5	220	(184, 264)	178	(144, 222)	1.2	(0.93, 1.64)
6A ¶	1366	(1122, 1663)	400	(306, 524)	3.4	(2.45, 4.77)
6B	1345	(1113, 1625)	875	(689, 1111)	1.5	(1.14, 2.08)
7F	748	(653, 857)	719	(598, 865)	1.0	(0.83, 1.31)
9V	848	(731, 984)	824	(694, 977)	1.0	(0.82, 1.29)
14	711	(580, 872)	869	(677, 1115)	0.8	(0.59, 1.13)
18C	1115	(925, 1344)	912	(707, 1177)	1.2	(0.89, 1.67)
19A	471	(408, 543)	390	(318, 477)	1.2	(0.94, 1.55)
19F	819	(697, 963)	626	(504, 779)	1.3	(1.00, 1.71)
23F	216	(169, 277)	84	(62, 114)	2.6	(1.74, 3.79)