Phase III, Open, Comparative Study in Healthy Adults Aged 18-50 Years Administered With Hepatyrix or Havrix + Typherix or Tiphim Vi, to Compare Reactogenicity and Immunogenicity.

Condition(s) targeted: Prophylaxis of Typhoid and Hepatitis A and B

Intervention: Combined Vi polysaccharide typhoid vaccine and hepatitis A vaccine- Hepatyrix (Biological)

Phase: Phase 2/Phase 3

Status: Active, not recruiting

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
Clinical Trials, Study Director, Affiliation: GlaxoSmithKline

To evaluate the immunogenicity, reactogenicity and safety of Hepatyrix when compared to the concomitant administration of Typherix and Havrix, and when compared to the administration of monovalent vaccines, Havrix or Typhim Vi. Furthermore, the study will evaluate the persistence of anti-Vi and anti-HAV antibodies up to 36 months after administration of the first dose of the study vaccine.

Official title: A Phase III, Open, Randomized, Multicentric Study to Compare the Reactogenicity and Immunogenicity of GlaxoSmithKline Biologicals’ Combined Vi Polysaccharide Typhoid Vaccine and Inactivated Hepatitis A Vaccine, Hepatyrix, to That Elicited by GlaxoSmithKline Biologicals’ Hepatitis A Vaccine, Havrix Administered Singly or Concomitantly With GlaxoSmithKline Biologicals’ Vi Polysaccharide Vaccine, Typherix, and to That Elicited by Aventis Pasteur’s Monovalent Vi Polysaccharide Vaccine, Typhim Vi, Administered Intramuscularly to Healthy Subjects Aged 18-65 Years.

Study design: Prevention, Randomized, Open Label, Active Control, Parallel Assignment, Safety Study

Primary outcome:

• Anti-Vi seropositivity rates (i.e., percentage of subjects with anti-Vi antibody titres > or = 150 EL.U/ml) at Month 1 after administration of study vaccine (Comparison of Hepatyrix versus concomitant Havrix+Typherix and Hepatyrix versus Typhim Vi).

• Anti-HAV seropositivity rates (i.e., percentage of subjects with anti-HAV antibody titres >or = 15 mIU/ml) at Month 1 after administration of study vaccine, (Comparison of Hepatyrix versus concomitant Havrix+Typherix and Hepatyrix versus Havrix).

Secondary outcome:

"• Anti-Vi seropositivity rates at Day 14, Month 6 and Month 7 and GMTs at Day 14, Month 1, Month 6 and Month 7 after administration of study vaccine.

• Anti-HAV seropositivity rates at Day 14, Month 6 and Month 7 and GMTs at Day 14, Month 1, Month 6 and Month 7 after administration of study vaccine.

• Anti-Vi and anti-HAV seropositivity rates and GMTs at Months 12, 24, 36 after administration of study vaccine.

• Occurrence and intensity of solicited local symptoms after vaccination (Day 0 to 4).

• Occurrence, intensity and relationship of solicited general symptoms after vaccination (Day 0 to 4).

• Occurrence, intensity and relationship to vaccination of unsolicited signs and symptoms after vaccination (Day 0 to 30).

• Occurrence, intensity and relationship to vaccination of serious adverse events (SAEs) during the study period and during the follow-up period up to Months 12, 24 and 36 after administration of study vaccine."

Detailed description: Open, randomised, self-contained, multicentric, multinational study. The three comparators in this study are Havrix, Typherix, Typhim Vi. In the primary phase, subjects included in Hepatyrix at Day 0 and Havrix at Month 6; subjects included in Havrix+Typherix Group having received concomitantly Havrix and Typherix at Day 0 and Havrix at Month 6; subjects included in the Havrix Group having received Havrix at Day 0 and Month 6 and on a voluntary basis, a single dose of Typherix at Month 7; subjects included in the Typhim Vi Group having received Typhim Vi at Day 0. Subjects randomized to receive Typhim Vi at Day 0 were given on a voluntary basis and at the discretion of the investigator, the first dose of Havrix at Month 6 and the second Havrix dose at Month 12 follow-up visit. The long-term follow-up studies at approximately 12, 24 and 36 months after the primary vaccination of Vi typhoid vaccine involves taking a blood sample to assess antibody persistence and a retrospective safety follow-up.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

"Inclusion criteria

- Written informed consent will be obtained from the subject prior to entry into the

study.

- Free of obvious health problems as established by medical history and clinical

examination before entering into the study.

- Seronegative for anti-HAV antibodies.

- If the subject is female, she must be of non-childbearing potential, i. e., either

surgically sterilized or one year post-menopausal; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions (e. g., intrauterine contraceptive device; oral contraceptives; diaphragm or condom in combination with contraceptive jelly, cream or foam; Norplant® or DepoProvera®) for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series.• Subjects having received the study vaccines 36 months earlier.

Exclusion criteria for enrolment

- Use of any investigational or non-registered drug or vaccine other than the study

vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.

- Chronic administration (defined as more than 14 days) of immunosuppressants or other

immune-modifying drugs within six months prior to the first vaccine dose. (For corticosteroids, this will mean prednisone, or equivalent, >or = 0. 5 mg/kg/day. Inhaled and topical steroids are allowed.).

- Planned administration/Administration of a vaccine not foreseen by the study protocol

within 30 days of the first dose of vaccine(s).

- Administration of immunoglobulins and/or any blood products within the three months

preceding the first dose of study vaccine or planned administration during the study period.

- History of chronic alcohol consumption and/or intravenous drug abuse.

- Previous vaccination against hepatitis A.

- Previous vaccination against typhoid fever.

- History of hepatitis A.

- Previous diagnosis, confirmed by a physician, of Salmonella typhi infection.

- History of non-response to hepatitis A and or typhoid vaccine.

- Any confirmed or suspected immunosuppressive or immunodeficient condition, including

human immunodeficiency virus (HIV) infection.

- A family history of congenital or hereditary immunodeficiency.

- History of allergic disease or reactions likely to be exacerbated by any component of

the vaccine.

- Acute disease at the time of enrolment. (Acute disease is defined as the presence of a

moderate or severe illness with or without fever. All vaccines can be administered to persons with a minor illness such as diarrhoea, mild upper respiratory infection with or without low-grade febrile illness, i. e., axillary temperature < 99. 5 °F (37. 5 °C)

- Female planning to become pregnant during the primary study period (up Month 7).

- Pregnant or lactating female.

- Planned travel to areas of high endemicity for hepatitis A and/ or typhoid fever

during the primary study period (up Month 7).

"

Munich, Germany

Last updated: September 15, 2005