Havrix

Pediatric Effectiveness Studies

• A double-blind, randomized controlled study evaluated the protective efficacy of Havrix in school children 1 to 16 years of age in Thailand who were at high risk for HAV infection. Patients (N=40,119) were randomly assigned to receive either Havrix 360 EL.U. or Engerix-B 10 mcg at 0, 1, and 12 months. Patients entered surveillance at Day 138 and were observed for an additional 8 months.

• There were 32 cases of clinical hepatitis A identified in the control group and 2 cases identified in the Havrix group using the protocol-defined endpoint (≥2 days absence from school, ALT level >45 U/mL, and a positive result in the HAVAB-M test).

• Using the protocol-defined endpoint, the vaccine efficacy rate for Havrix was 94% (95% CI, 74-98) for prevention of clinical hepatitis A.

• Using additional virological and serological analyses post hoc, the vaccine efficacy rate for Havrix was 84% (95% CI, 60-94) for prevention of clinical hepatitis A.

Immunogenicity in Children and Adolescents

Immune Response to Havrix 720 EL.U./0.5 mL at Age 11 to 25 Months (Study HAV 210)

Prospective, open-label, multicenter study

• The study included 1084 children who received 1 of 5 groups:

• (1) Children aged 11 to 13 months who received Havrix on a 0- and 6-month schedule; 

• (2) Children aged 15 to 18 months who received Havrix on a 0- and 6-month schedule; 

• (3) Children aged 15 to 18 months who received Havrix coadministered with Infanrix and Haemophilus b (Hib) conjugate vaccine (no longer U.S.-licensed) at Month 0 and HAVRIX at Month 6; 

• (4) Children aged 15 to 18 months who received Infanrix coadministered with Hib conjugate vaccine at Month 0 and Havrix at Months 1 and 7; 

• (5) Children aged 23 to 25 months who received Havrix on a 0- and 6-month schedule.

• Vaccine response rates were similar among the 3 age-groups that received Havrix. One month after the second dose of Havrix, the GMT in each of the younger age-groups (aged 11 to 13 months and 15 to 18 months) was shown to be similar to that achieved in the 23- to 25-month age-group.

3 Additional Studies – HAV 232, HAV 220, HAV 231

• Children received either 2 doses of Havrix alone or the first dose of Havrix concomitantly with other routinely recommended US-licensed vaccines after a second dose of Havrix.

• There was no evidence for interference with the anti-HAV response when Havrix was concomitantly administered with these vaccines.

Immune Response to Havrix 360 EL.U. among Individuals Aged 2 to 18 Years

• 6 clinical studies evaluated the immune response of Havrix in 762 patients 2 to 18 years of age who received 2 doses of Havrix (360 EL.U.) given 1 month apart. 

• After a third dose of Havirx was administered 6 months following the initial dose, all patients were seropositive (anti-HAV ≥20 mIU/mL) 1 month following the third dose, with GMTs rising to a range of 3,388 to 4,643 mIU/mL. In 1 study in which children were followed for an additional 6 months, all subjects remained seropositive. 

Immune Response to Havrix 720 EL.U./0.5 mL among Individuals Aged 2 to 19 Years

• 4 clinical studies evaluated the immune response of Havrix in 314 children and adolescents 2 to 19 years of age who received 2 doses of Havrix 720 EL.U./0.5mL given 6 months apart.

• One month after the first dose, seroconversion (anti-HAV ≥20 mIU/mL [lower limit of antibody measurement by assay]) ranged from 96.8% to 100%, with GMTs of 194 mIU/mL to 305 mIU/mL.

• In studies in which sera were obtained 2 weeks following the initial dose, seroconversion ranged from 91.6% to 96.1%. One month following the booster dose at Month 6, all subjects were seropositive, with GMTs ranging from 2,495 mIU/mL to 3,644 mIU/mL.

• In an additional study in which the booster dose was delayed until 1 year following the initial dose, 95.2% of the subjects were seropositive just prior to administration of the booster dose. One month later, all subjects were seropositive, with a GMT of 2,657 mIU/mL.

Immunogenicity in Adults

• 3 clinical studies evaluated the immunogenicity of Havrix in more than 400 healthy adults 18 to 50 years of age who received a single 1440 EL.U. dose of Havrix. All patients were seronegative for hepatitis A antibodies at baseline.

• Specific humoral antibodies against HAV were elicited in more than 96% of subjects when measured 1 month after vaccination. By Day 15, 80% to 98% of vaccinees had already seroconverted (anti-HAV ≥20 mIU/mL [lower limit of antibody measurement by assay]). 

• GMTs of seroconverters ranged from 264 to 339 mIU/mL at Day 15 and increased to a range of 335 to 637 mIU/mL by 1 month following vaccination. The GMTs obtained following a single dose of Havrix are at least several times higher than that expected following receipt of immune globulin.

• In 2 clinical trials in which a booster dose of 1440 EL.U. was given 6 months following the initial dose, 100% of vaccinees (n = 269) were seropositive 1 month after the booster dose, with GMTs ranging from 3,318 mIU/mL to 5,925 mIU/mL. 

• In a subset of vaccinees (n = 89), a single dose of Havrix 1440 EL.U. elicited specific anti-HAV neutralizing antibodies in more than 94% of vaccinees when measured 1 month after vaccination. These neutralizing antibodies persisted until Month 6. One hundred percent of vaccinees had neutralizing antibodies when measured 1 month after a booster dose given at Month 6.

• A clinical study evaluated the immunogenicity of Havrix in patients with chronic liver disease of various etiologies (eg, chronic hepatitis B, chronic hepatitis C, moderate chronic liver disease of other etiology, alcoholic cirrhosis, autoimmune hepatitis, chronic hepatitis/cryptogenic cirrhosis, hemochromatosis, primary biliary cirrhosis, primary sclerosing cholangitis, and unspecified).

• At each time point, GMTs were lower for patients with chronic liver disease vs healthy patients. Seroconversion rates in adults with chronic liver disease were lower one month after the first dose vs healthy adults. However, 1 month after the booster dose at Month 6, seroconversion rates were similar in all groups; rates ranged from 94.7% to 98.1%.

Duration of Immunity

• The duration of immunity has not been established.

Immune Response to Concomitantly Administered Vaccines

Concomitant Administration with DTaP and Hib Conjugate Vaccine (Study HAV 232)

• In a US multicenter study, 468 children aged 15 months were randomly assigned to receive: Havrix concomitantly with Infanrix and Hib conjugate vaccine; or Infanrix and Hib conjugate vaccine alone followed by a first dose of Havrix 1 month later; or Havrix alone.

• When Havrix was administered concomitantly with Infanrix and Hib conjugate vaccine relative to Infanrix and Hib conjugate vaccine administered together, there was no evidence for reduced antibody response to diphtheria and tetanus toxoids, pertussis antigens, or Hib.

Concomitant Administration with Pneumococcal 7-Valent Conjugate Vaccine (Study HAV 220)

• In a US multicenter study, 433 children aged 15 months were randomly assigned to receive: Havrix concomitantly with PCV-7 vaccine; or Havrix alone; or PCV-7 alone.

• There was no evidence for reduced antibody response to PCV-7 when Havrix was administered with PCV-7 relative to PCV-7 alone.

Concomitant Administration with MMR and Varicella Vaccines (Study HAV 231) 

• In a US multicenter study, there was no evidence for interference in the immune response to MMR and varicella vaccines (the percentage of subjects with pre-specified seroconversion/seroresponse levels) administered to subjects aged 15 months concomitantly with Havrix relative to the response when MMR and varicella vaccines are administered without Havrix.