Vaccine Information: Prevnar 20 (Page 5 of 6)

14.3 Prevnar 20 Clinical Trials in Individuals 18 Years of Age and Older

Immunogenicity of Prevnar 20 in Pneumococcal Vaccine Naïve Individuals

Prevnar 20 effectiveness in adults against invasive pneumococcal disease caused by the 20 vaccine serotypes and against pneumonia caused by the 13 serotypes in Prevnar 13 was demonstrated based on comparative immunogenicity to US-licensed pneumococcal vaccines (Prevnar 13 and PPSV23). Study 1, conducted in the United States and Sweden, was designed to evaluate immunologic noninferiority of Prevnar 20 to Prevnar 13 (for the 13 original S. pneumoniae serotypes) and PPSV23 (for the 7 new S. pneumoniae serotypes) in pneumococcal vaccine naive individuals ≥60 years of age. Antibody responses elicited by Prevnar 20 and the control pneumococcal vaccines were measured by serotype-specific serum OPA assays for the 20 pneumococcal serotypes at 1-month post-vaccination. OPA assays were used to measure functional antibodies to S. pneumoniae.

Study 1 included healthy individuals and immunocompetent individuals with stable underlying conditions, including chronic cardiovascular disease, chronic pulmonary disease, renal disorders, diabetes mellitus, chronic liver disease, and medical risk conditions and behaviors (e.g., smoking) that are known to increase the risk of serious pneumococcal pneumonia and IPD. A stable medical condition was defined as a medical condition not requiring significant change in therapy in the previous 6 weeks (i.e., change to new therapy category due to worsening disease) or any hospitalization for worsening disease within 12 weeks before receipt of the study vaccine.

Comparison of Immune Responses of Prevnar 20 to Prevnar 13 and PPSV23 in Pneumococcal Vaccine Naïve Individuals ≥60 Years of Age

In a randomized, active-controlled, double-blind noninferiority clinical trial (Study 1) of Prevnar 20 in the United States and Sweden, pneumococcal vaccine -naïve individuals 18 years of age and older were enrolled into 1 of 3 cohorts based on their age at enrollment and randomized to receive either Prevnar 20 or control. Participants 60 years of age and older were randomly assigned (1:1 ratio) to Prevnar 20 followed 1 month later with saline placebo or to Prevnar 13 followed 1 month later with PPSV23.

Serotype-specific OPA GMTs were measured before the first vaccination and 1 month after each vaccination. Noninferiority of immune responses, OPA GMTs 1 month after vaccination, with Prevnar 20 to a control vaccine for a serotype was declared if the lower bound of the 2 sided 95% CI for the GMT ratio (Prevnar 20/Prevnar 13; Prevnar 20/PPSV23) for that serotype was greater than 0.5.

In individuals 60 years of age and older, immune responses to all 13 matched serotypes elicited by Prevnar 20 were noninferior to the immune responses to the serotypes elicited by Prevnar 13 one month after vaccination. Immune responses to 6 out of the 7 additional serotypes induced by Prevnar 20 were noninferior to the immune responses to these same serotypes induced by PPSV23 one month after vaccination. The response to serotype 8 missed the prespecified statistical noninferiority criterion by a small margin (the lower bound of the 2-sided 95% CI for the GMT ratio being 0.49 versus >0.50) (Table 13).

In supportive analyses, 77.8% of participants in the Prevnar 20 group achieved a ≥4-fold rise in serotype 8 OPA titers from before vaccination to 1 month post-vaccination.

Table 13. OPA GMTs 1 Month After Vaccination in Participants 60 Years of Age and Older Given Prevnar 20 Compared to Prevnar 13 for the 13 Matched Serotypes and PPSV23 for the 7 Additional Serotypes (Study 1)*^, †^, ‡^, §

Abbreviations: CI = confidence interval; GMT = geometric mean titer; LLOQ = lower limit of quantitation; N = number of participants; OPA = opsonophagocytic activity; PPSV23 = pneumococcal polysaccharide vaccine (23-valent).
* Study 1 was conducted in the United States and in Sweden (NCT03760146). † Noninferiority for a serotype was met if the lower bound of the 2-sided 95% CI for the GMT ratio (ratio of Prevnar 20/comparator) was greater than 0.5 (2-fold criterion for noninferiority). ‡ Assay results below the LLOQ were set to 0.5 × LLOQ in the analysis. § Evaluable immunogenicity population. ¶ GMTs, GMT ratios, and the associated 2-sided CIs were based on analysis of log-transformed OPA titers using a regression model with vaccine group, sex, smoking status, age at vaccination in years, and baseline log-transformed OPA titers.
	Prevnar 20 (N = 1157–1430)	Prevnar 13 (N = 1390–1419)	PPSV23 (N = 1201–1319)	Vaccine Comparison
	GMT ¶	GMT ¶	GMT ¶	GMT Ratio ¶ (95% CI) ¶
Serotype
1	123	154		0.80(0.71, 0.90)
3	41	48		0.85(0.78, 0.93)
4	509	627		0.81(0.71, 0.93)
5	92	110		0.83(0.74, 0.94)
6A	889	1165		0.76(0.66, 0.88)
6B	1115	1341		0.83(0.73, 0.95)
7F	969	1129		0.86(0.77, 0.96)
9V	1456	1568		0.93(0.82, 1.05)
14	747	747		1.00(0.89, 1.13)
18C	1253	1482		0.85(0.74, 0.97)
19A	518	645		0.80(0.71, 0.90)
19F	266	333		0.80(0.70, 0.91)
23F	277	335		0.83(0.70, 0.97)
Additional Serotypes
8	466		848	0.55(0.49, 0.62)
10A	2008		1080	1.86(1.63, 2.12)
11A	4427		2535	1.75(1.52, 2.01)
12F	2539		1717	1.48(1.27, 1.72)
15B	2398		769	3.12(2.62, 3.71)
22F	3666		1846	1.99(1.70, 2.32)
33F	5126		3721	1.38(1.21, 1.57)

Immunobridging in Pneumococcal Vaccine Naïve Individuals 18 Through 59 Years of Age

In Study 1 (described above), the effectiveness of Prevnar 20 in individuals 50 through 59 years of age and in individuals 18 through 49 years of age was inferred following comparison of the immune response to each of the 20 vaccine serotypes in each of these age groups to the corresponding serotype-specific immune responses in individuals 60 through 64 years of age following Prevnar 20 (immunobridging). In Study 1, pneumococcal vaccine-naïve participants 50 through 59 years of age and 18 through 49 years of age were randomly assigned (3:1 ratio) to receive 1 vaccination with Prevnar 20 or Prevnar 13. Serotype-specific OPA GMTs were measured before vaccination and 1 month after vaccination. A comparative analysis of Prevnar 20 in the younger age group versus Prevnar 20 in individuals 60 through 64 years of age for each vaccine serotype was performed to support the indication in individuals 18 through 49 years of age and 50 through 59 years of age. Immunobridging was to be declared successful if the lower bound of the 2-sided 95% CI for the GMT ratio (Prevnar 20 in participants 18 through 49 years of age/60 through 64 years of age and in participants 50 through 59 years of age/60 through 64 years of age) for the 20 serotypes was >0.5 (2-fold). Prevnar 20 elicited serotype-specific immune responses to each of the 20 vaccine serotypes in both of the younger age groups that were within 2-fold of the corresponding serotype-specific responses in individuals 60 through 64 years of age, when measured 1 month after vaccination (Table 14).

Table 14. Comparisons of OPA GMTs 1 Month After Prevnar 20 in Participants 18 Through 49 or 50 Through 59 Years of Age to Participants 60 Through 64 Years of Age (Study 1)*^, †^, ‡^, §

Abbreviations: CI = confidence interval; GMT = geometric mean titer; LLOQ = lower limit of quantitation; N = number of participants; OPA = opsonophagocytic activity; PPSV23 = pneumococcal polysaccharide vaccine 23-valent vaccine.
* Study 1 was conducted in the United States and in Sweden (NCT03760146). † Immunobridging for a serotype was met if the lower bound of the 2-sided 95% CI for the GMT ratio (ratio of younger age group/60 through 64 years of age group) was greater than 0.5 (2-fold success criterion). ‡ Assay results below the LLOQ were set to 0.5 × LLOQ in the analysis. § Evaluable immunogenicity population. ¶ GMTs, GMT ratios, and the associated 2-sided CIs were based on analysis of log-transformed OPA titers using a regression model with age group, sex, smoking status, and baseline log-transformed OPA titers. The comparisons between individuals 18 through 49 years of age and individuals 60 through 64 years of age and between individuals 50 through 59 years of age and individuals 60 through 64 years of age were based on separate regression models.
	18–49 Years (N = 251–317)	60–64 Years (N = 765–941)	18–49 Years Relative to 60–64 Years	50–59 Years (N = 266–320)	60–64 Years (N = 765–941)	50–59 Years Relative to 60–64 Years
	GMT ¶	GMT ¶	GMT Ratio ¶ (95% CI) ¶	GMT ¶	GMT ¶	GMT Ratio ¶ (95% CI) ¶
Serotype
1	163	132	1.23(1.01, 1.50)	136	132	1.03(0.84, 1.26)
3	42	42	1.00(0.87, 1.16)	43	41	1.06(0.92, 1.22)
4	1967	594	3.31(2.65, 4.13)	633	578	1.10(0.87, 1.38)
5	108	97	1.11(0.91, 1.36)	85	97	0.88(0.72, 1.07)
6A	3931	1023	3.84(3.06, 4.83)	1204	997	1.21(0.95, 1.53)
6B	4260	1250	3.41(2.73, 4.26)	1503	1199	1.25(1.00, 1.56)
7F	1873	1187	1.58(1.30, 1.91)	1047	1173	0.89(0.74, 1.07)
9V	6041	1727	3.50(2.83, 4.33)	1726	1688	1.02(0.83, 1.26)
14	1848	773	2.39(1.93, 2.96)	926	742	1.25(1.01, 1.54)
18C	4460	1395	3.20(2.53, 4.04)	1805	1355	1.33(1.06, 1.68)
19A	1415	611	2.31(1.91, 2.81)	618	600	1.03(0.85, 1.25)
19F	655	301	2.17(1.76, 2.68)	287	290	0.99(0.80, 1.22)
23F	1559	325	4.80(3.65, 6.32)	549	328	1.68(1.27, 2.22)
Additional Serotypes
8	867	508	1.71(1.38, 2.12)	487	502	0.97(0.78, 1.20)
10A	4157	2570	1.62(1.31, 2.00)	2520	2437	1.03(0.84, 1.28)
11A	7169	5420	1.32(1.04, 1.68)	6417	5249	1.22(0.96, 1.56)
12F	5875	3075	1.91(1.51, 2.41)	3445	3105	1.11(0.88, 1.39)
15B	4601	3019	1.52(1.13, 2.05)	3356	2874	1.17(0.88, 1.56)
22F	7568	4482	1.69(1.30, 2.20)	3808	4228	0.90(0.69, 1.17)
33F	7977	5693	1.40(1.10, 1.79)	5571	5445	1.02(0.81, 1.30)

Immunogenicity of Prevnar 20 in Individuals Previously Vaccinated With Pneumococcal Vaccine

A randomized, open-label clinical trial (Study 6) described immune responses to Prevnar 20 in individuals 65 years of age and older previously vaccinated with PPSV23 (≥1 to ≤5 years prior to enrollment), previously vaccinated with Prevnar 13 (≥6 months prior to enrollment), or previously vaccinated with Prevnar 13 followed by PPSV23 (with PPSV23 vaccination ≥1 year prior to enrollment). Participants in this clinical trial previously vaccinated with Prevnar 13 (Prevnar 13 only or followed by PPSV23) were enrolled at sites in the United States and participants previously vaccinated with PPSV23 only were also enrolled from Swedish sites (35.5% in that category). Immune responses elicited by Prevnar 20 were measured by an OPA assay.

OPA GMTs in participants who received PPSV23 1 to 5 years prior to Prevnar 20 were diminished compared to OPA GMTs in participants who received Prevnar 13 at least 6 months previously and compared to OPA GMTs in participants who received Prevnar 13 followed by PPSV23, with the last PPSV23 dose given at least 1 year prior to Prevnar 20.