VAQTA ADULT Suspension for injection Ref.[8207] Active ingredients: Hepatitis A, inactivated vaccine

Pharmacotherapeutic group: viral vaccines, hepatitis A, inactivated, whole virus
ATC code: J07BC02

VAQTA Adult contains inactivated virus of a strain which was originally derived by further serial passage of a proven attenuated strain. The virus is grown, harvested, highly purified, formalin inactivated, and then adsorbed onto amorphous aluminum hydroxyphosphate sulphate.

Mechanism of action

Hepatitis A vaccine elicits circulating neutralising antibodies to Hepatitis A virus sufficient to confer protection against the virus.

Clinical efficacy and safety

Clinical studies showed seroconversion rates were 95% in adults within 4 weeks after the recommended primary dose. In a sub-set of these individuals ≥60 years of age, data indicate that 88% (n=64) seroconverted by week 4 after the primary dose.

In adults, seropositivity has been shown to persist up to 18 months after a single 50U dose. Persistence of immunologic memory was demonstrated with a substantial anamnestic antibody response to a booster dose of 50U given 6 to 18 months after the primary dose to adults. The data regarding the subjects more than 60 years of age are limited.

Antibody persistence

In studies of healthy adults (18 to 41 years of age) who received an initial 50U dose of VAQTA at Day 0 and a subsequent 50U dose 6 months later, the hepatitis A antibody response to date has been shown to persist to at least 6 years. After an initial decline over 2 years, the GMTs appeared to plateau during the 2 to 6 year period.

Data available from long-term studies up to 10 years on the persistence of HAV antibodies after 2 doses of VAQTA in healthy, immunocompetent subjects up to 41 years of age allows prediction that based on mathematical modelling at least 99% of subjects will remain seropositive (≥10 mIU anti-HAV/ml) at least 25 years after vaccination.

Based on this analysis, an additional vaccination following complete primary immunisation with 2 doses appears to be unnecessary. However, decisions regarding additional vaccination should be based on risk-benefit for the individual.

Interchangeability of the booster dose

A clinical study in 537 healthy adults, 18 to 83 years of age, evaluated the immune response to a booster dose of VAQTA Adult and a comparable licensed inactivated hepatitis A vaccine given at 6 or 12 months following initial dose of the comparator vaccine. When VAQTA Adult was given as a booster dose in this case it produced an equivalent immune response and was generally well tolerated. (See section 4.2.)

Concomitant use with immunoglobulin

Concurrent administration to healthy adults (18 to39 years of age) of 50 U/1.0 mL of VAQTA Adult with immunoglobulin (IG, 0.06 mL/kg) was evaluated in a clinical study. The seroconversion rate at week 24 in the vaccine alone group (97%) was higher than in the vaccine plus IG group (92% p = 0.050) but rose to 100% in both groups one month post booster.

Concomitant use with other vaccines

A controlled clinical study was conducted with 240 healthy adults, 18 to 54 years of age, who were randomised to receive either

• VAQTA Adult, yellow fever and polysaccharide typhoid vaccines concomitantly at separate injection sites or
• yellow fever and polysaccharide typhoid vaccines concomitantly at separate injection sites or
• VAQTA Adult alone.

The seropositivity rate (SPR) for hepatitis A when VAQTA Adult, yellow fever and polysaccharide typhoid vaccines were administered concomitantly was generally similar to when VAQTA Adult was given alone. However the GMTs for hepatitis A were reduced when the three vaccines were administered concomitantly. Clinically, this reduction in GMTs may be less relevant compared to the benefits of concomitant administration. The antibody response rates for yellow fever and typhoid were equivalent when yellow fever and polysaccharide typhoid vaccines were administered concomitantly with and without VAQTA Adult. The concomitant administration of these three vaccines at separate injection sites was generally well tolerated. The addition of VAQTA Adult to the standard practice of administering yellow fever and typhoid vaccines does not increase the rates of injection site and systemic adverse reactions. (See section 4.2.)

Subcutaneous administration

In a clinical study with 114 healthy seronegative adults who received subcutaneous administration of VAQTA Adult (50U), at 4 weeks following the first dose, the SPR was 78%, and the GMT was 21 mIU/mL. At 24 weeks following the first dose and just prior to the second subcutaneous injection, the SPR was 95%, and the GMT was 153 mIU/mL. At 4 weeks following the second subcutaneous injection, the SPR was 100%, and the GMT was 1,564 mIU/mL; the GMT was 2,287 mlU/mL in subjects less than 30 years of age compared with a GMT of 1,122 mlU/mL in subjects 30 years of age and older. The kinetics of seropositivity were slower for the first subcutaneous dose of VAQTA Adult compared with historical data for intramuscular administration. At 24 weeks following the first subcutaneous dose, the SPR was similar to the historical data at 4 weeks after the initial intramuscular dose. However, at 4 weeks following the second subcutaneous dose, the SPR was similar to the historical data 4 weeks after the second dose with intramuscular administration. Subcutaneous administration of VAQTA Adult was generally well tolerated.

Administration in HIV-infected adults

In a clinical study with 180 adults, 60 HIV-positive (20 to 45 years of age) and 90 HIV-negative adults (21 to 53 years of age) received VAQTA Adult (50U) and 30 HIV-positive adults (22 to 45 years of age) received placebo. At 4 weeks following the first dose of VAQTA Adult, the SPR was 61% for HIV-positive adults and 90% for HIV-negative adults. At 28 weeks following the first dose (4 weeks following the second dose) of VAQTA Adult, the SPRs were satisfactory for all groups: 94% ( GMT of 1,060 mIU/mL) in HIV-positive and 100% (GMT of 3,602 mIU/mL) in HIV-negative adults. Furthermore, in the HIV-positive group receiving VAQTA Adult, the SPR was 100% (GMT of 1,959 mIU/mL) in subjects with CD4 cell counts ≥300 cell/mm³; however, the SPR was 87% (GMT of 517 mIU/mL) in subjects with CD4 cell counts <300 cell/mm³. Three HIV-positive adults with CD4 cell counts <100 cells/mm³ did not seroconvert after receipt of 2 doses of vaccine. The kinetics of the immune response were slower in the HIV-positive group compared with the HIV-negative group. There was an increased rate of local and systemic adverse effects reported in HIV-positive versus HIV-negative adults. In HIV-positive adults, administration of VAQTA Adult did not appear to adversely affect the CD4 cell counts and HIV RNA burden.

Post-marketing safety study

In a post-marketing safety study, conducted at a large health maintenance organisation in the United States, a total of 29,587 individuals ≥ 18 years of age received 1 or 2 doses of VAQTA Adult. Safety was monitored by reviewing medical records that tracked emergency room and outpatient visits, hospitalisations and deaths. There was no serious, vaccine-related, adverse event identified among the 29,587 individuals in this study. There was no non-serious, vaccine-related, adverse event resulting in outpatient visits, with the exception of diarrhoea/gastroenteritis in adults at a rate of 0.5%. There was no vaccine-related, adverse event identified that had not been reported in earlier clinical trials with VAQTA Adult.