Vaccine Information: Shingrix (Page 4 of 5)

14.4 Immunological Evaluation to Support Dosing Schedule

A measure of the immune response that confers protection against HZ is unknown. Anti-gE antibody levels were measured by anti-gE enzyme-linked immunosorbent assay (gE ELISA) and were used to support the dosing schedule.

In an open-label clinical study, 238 subjects 50 years and older received SHINGRIX on either a 0- and 2-month or 0- and 6-month schedule. Non-inferiority of the 0- and 6-month schedule compared with the 0- and 2-month schedule based on anti-gE ELISA GMCs 1 month after the second dose was demonstrated.

14.5 Concomitant Administration with Influenza Vaccine

In an open-label clinical study, subjects 50 years and older received 1 dose each of SHINGRIX and FLUARIX QUADRIVALENT (QIV) at Month 0 and 1 dose of SHINGRIX at Month 2 (n = 413), or 1 dose of QIV at Month 0 and 1 dose of SHINGRIX at Months 2 and 4 (n = 415). There was no evidence for interference in the immune response to any of the antigens contained in SHINGRIX or the coadministered vaccine.

14.6 Efficacy in Immunocompromised Adults Aged 18 Years and Older

The efficacy of SHINGRIX was evaluated in one Phase 3 randomized, placebo-controlled, observer-blind clinical study in immunocompromised adults aged ≥18 years who received an auHSCT 50 to 70 days prior to Dose 1 and who were expected to receive prophylactic antiviral therapy for ≤6 months post-transplant. The efficacy of SHINGRIX was calculated post-hoc in another randomized, placebo-controlled, observer-blind study in subjects with hematologic malignancies who received Dose 1 of SHINGRIX or placebo during or within 6 months of completing immunosuppressive chemotherapy. Each of these studies was conducted in the following regions: North America, Latin America, Europe, Asia, Africa (auHSCT study only), and Australia/New Zealand.

Efficacy in Subjects Aged 18 Years and Older: auHSCT Recipients

In the auHSCT study, subjects were followed for the development of HZ and PHN for a median of 21 months (range: 0 to 49.4 months). Suspected HZ cases were followed prospectively for the development of PHN as in Studies 1 and 2.

The primary efficacy analysis population (mTVC) for the auHSCT study included 1,721 subjects who received 2 doses of either SHINGRIX or placebo and did not develop a confirmed case of HZ within 1 month after the second dose. Confirmed HZ cases were determined by either PCR (83.7%) or by a Clinical Evaluation Committee (16.3%).

Efficacy against Herpes Zoster: Compared with placebo, SHINGRIX significantly reduced the risk of developing HZ in auHSCT recipients aged 18 years and older (Table 8).

Table 8. Efficacy of SHINGRIX on Incidence of Herpes Zoster Compared with Placebo in Immunocompromised Adults Aged ≥18 Years (mTVCa)
auHSCT = Autologous, hematopoietic, stem cell transplant.N = Number of subjects included in each group; n = Number of subjects having at least 1 confirmed HZ episode; HZ = Herpes zoster; CI = Confidence Interval.a mTVC = Modified Total Vaccinated Cohort, defined as subjects who received 2 doses (0 and 1 to 2 months) of either SHINGRIX or placebo and did not develop a confirmed case of HZ within 1 month after the second dose. Follow-up was censored at the time of treatment for relapse.b NCT01610414.c Primary study endpoint was based on confirmed HZ cases in subjects aged ≥18 years.

Clinical Studies

Age Group (Years)

SHINGRIX

Placebo

% Efficacy (95% CI)

N

n

Incidence Rate of HZ per 1,000 Person-Years

N

n

Incidence Rate of HZ per 1,000 Person-Years

auHSCTb

Overall (≥18)c

870

49

30.0

851

135

94.3

68.2

(55.5, 77.6)

18-49

213

9

21.5

212

29

76.0

71.8

(38.7, 88.3)

≥50

657

40

33.0

639

106

100.9

67.3

(52.6, 77.9)

Efficacy in Subjects Aged 18 Years and Older with Hematologic Malignancies

In the study of hematologic malignancies, the mean age was 57 years. The majority of subjects were White (71%), followed by Asian (25%), Black (0.4%), and other racial groups (4%); 5% were of American Hispanic or Latino ethnicity; and 41% were female. Subjects were followed for the development of HZ for a median of 11.1 months (range: 0 to 15.6 months). PHN was not assessed as a study endpoint.

In the hematologic malignancy study, the population for the post hoc efficacy analysis included 515 subjects who received 2 doses of either SHINGRIX or placebo and did not develop a confirmed case of HZ within 1 month after the second dose. Confirmed HZ cases were determined by either PCR (81.3%) or by a Clinical Evaluation Committee (18.7%). The post hoc analysis showed SHINGRIX was 87.2% (95% CI [44.2; 98.6]) effective against development of HZ. The incidence rate of HZ per 1,000 person-years was 8.5 versus 66.2 in the SHINGRIX and placebo groups, respectively.

Additional Efficacy Endpoints Evaluated in the auHSCT Study

Efficacy against Postherpetic Neuralgia: In a descriptive analysis, including all subjects aged ≥18 years in the mTVC, 1 case of PHN was reported in the vaccine group compared with 9 cases reported in the placebo group. Vaccine efficacy against PHN was 89.3% (95% CI: [22.5; 99.8]). The benefit of SHINGRIX in the prevention of PHN can be attributed to the effect of the vaccine on the prevention of HZ.

Herpes Zoster-Associated Pain: Subjects with suspected HZ rated their “worst” HZ-associated pain on a 10-point scale. Among subjects with confirmed HZ, 37 out of 49 subjects (75.5%) receiving SHINGRIX and 120 out of 135 subjects (88.9%) receiving placebo rated their “worst” HZ-associated pain as 3 or greater. In this subset of subjects, the median duration of “worst” HZ associated pain was 14 and 24 days, among SHINGRIX and placebo recipients, respectively.

16 HOW SUPPLIED/STORAGE AND HANDLING

SHINGRIX is supplied as 2 components: A single-dose vial of lyophilized gE antigen component (powder) and a single-dose vial of adjuvant suspension component (liquid) (packaged without syringes or needles).

Table 9. Product Presentations for SHINGRIX

Presentation

Carton NDC Number

Components

Adjuvant Suspension Component (liquid)

Lyophilized gE Antigen Component (powder)

An outer carton of 1 dose

58160-819-12

Vial 1 of 2

NDC 58160-829-01

Vial 2 of 2

NDC 58160-828-01

An outer carton of 10 doses

58160-823-11

10 vials

NDC 58160-829-03

10 vials

NDC 58160-828-03

16.1 Storage before Reconstitution

Adjuvant suspension component vials: Store refrigerated between 2° and 8°C (36° and 46°F). Protect vials from light. Do not freeze. Discard if the adjuvant suspension has been frozen.

Lyophilized gE antigen component vials: Store refrigerated between 2° and 8°C (36° and 46°F). Protect vials from light. Do not freeze. Discard if the antigen component has been frozen.

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