Clinical trial NCT00943878
Conditions: Influenza
Keywords: H1N1, influenza A viruses, vaccine, elderly, TIV
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2009-08-01; Completion date: 2010-04-01
Enrollment: 805 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to assess the safety and immune response (body's defense against disease) to an experimental H1N1 influenza vaccine against the 2009 H1N1 virus. This study will help determine how the H1N1 flu shot should be given with the seasonal flu shot to make it most effective. Participants will include up to 850 healthy adults, ages 18 and older. Participants will receive 2 H1N1 vaccines in addition to placebo (inactive substance) and the seasonal flu shot over 3 study visits about 21 days apart. Study procedures include: medical history, physical exam, maintaining a memory aid, and blood sample collection. Participants will be involved in the study for about 8 months.

Detailed description:
Recently, a novel swine-origin influenza A/H1N1 virus was identified as a significant cause of febrile respiratory illnesses in Mexico and the United States. It rapidly spread to many countries around the world, prompting the World Health Organization to declare a pandemic on June 11, 2009. Data from several cohorts in different age groups that received licensed trivalent seasonal influenza vaccines suggest that these vaccines are unlikely to provide protection against the new virus. Adults are more likely to have measurable levels of serum hemagglutination inhibition assay (HAI) or neutralizing antibody than are children. These data indicate the need to develop vaccines against the new H1N1 strain and suggest that different vaccine strategies (e.g., number of doses, need for adjuvant) may be appropriate for persons in different age groups. If the novel influenza H1N1 2009 virus continues to circulate, it is possible that it will co-circulate with the non-pandemic seasonal influenza strains. In this situation, it might be beneficial to co-administer an H1N1 vaccine concurrent with the seasonal inactivated influenza vaccine. This protocol explores if vaccination with the 2009-2010 licensed seasonal trivalent influenza vaccine (TIV) has an effect on antibody response to the novel influenza H1N1 2009 virus and examines if receiving the H1N1 vaccine either concurrent with, prior to, or following the seasonal influenza vaccine affects the antibody response to the seasonal influenza vaccine. This is a randomized, double-blinded, Phase II study in up to 850 healthy males and non-pregnant females, aged 18 and older. The study investigates the safety, reactogenicity, and immunogenicity of an inactivated influenza H1N1 virus vaccine when given concurrent with or sequentially with (before or after) TIV. The primary safety objective is to assess the safety of the unadjuvanted, inactivated H1N1 influenza vaccine when administered either concurrent with, prior to, or following licensed seasonal influenza vaccination. The primary immunogenicity objective is to assess the effect of TIV on antibody response to unadjuvanted, inactivated influenza H1N1 vaccine as assessed by hemagglutination inhibition assay (HAI), stratified by age of recipient. The secondary objective is immunogenicity, to assess the effect of H1N1 vaccine administration on antibody response to TIV as assessed by HAI, stratified by age of recipient. Subjects will be randomized into 4 groups, stratified by age (200 subjects per group with 100 subjects per age stratum, 18-64 or greater than or equal to 65 years of age). Group 1 will receive two 15 microgram (mcg) doses of H1N1 vaccine at Days 0 and 21 followed by TIV on Day 42. Group 2 will receive two 15 mcg doses of H1N1 vaccine of which the first dose is administered concurrently with TIV. Group 3 will receive two 15 mcg doses of H1N1 vaccine of which the second dose is administered concurrently with TIV. Group 4 will receive TIV administered on Day 0 followed by two 15 mcg doses of H1N1 vaccine on Days 21 and 42. In order to maintain the blind, subjects will also receive a placebo (normal saline) so that two products will be administered at both Days 0 and 21, and one product will be administered at Day 42 for all groups. Following immunization, safety will be measured by assessment of adverse events for 21 days following the last vaccination (Day 42 for those who do not receive the second dose), serious adverse events and new-onset chronic medical conditions for 8 months post the first vaccination (Day 222), and reactogenicity to the vaccines for 8 days following each vaccination (Day 0-7). Immunogenicity testing will include HAI

Arms: arm 1: 200 subjects (100 ages 18-64 years and 100 aged greater than or equal to 65 years) to receive: Day 0, 15 mcg H1N1 Vaccine + placebo; Day 21, 15 mcg H1N1 Vaccine + trivalent influenza vaccine (TIV); and Day 42, placebo. arm 2: 200 subjects (100 ages 18-64 years and 100 aged greater than or equal to 65 years) to receive: Day 0, 15 mcg H1N1 Vaccine + placebo; Day 21, 15 mcg H1N1 Vaccine + placebo; and Day 42, trivalent influenza vaccine (TIV). arm 3: 200 subjects (100 ages 18-64 years and 100 aged greater than or equal to 65 years) to receive: Day 0, 15 mcg H1N1 Vaccine + trivalent influenza vaccine (TIV); Day 21, 15 mcg H1N1 Vaccine + placebo; and Day 42, placebo. arm 4: 200 subjects (100 ages 18-64 years and 100 aged greater than or equal to 65 years) to receive: Day 0, trivalent influenza vaccine (TIV) + placebo; Day 21, 15 mcg H1N1 Vaccine + placebo; and Day 42, 15 mcg H1N1 vaccine.
Interventions: intervention 1: Trivalent inactivated influenza vaccine intervention 2: Inactivated H1N1 Vaccine intervention 3: Placebo
Intervention descriptions: intervention 1: Licensed trivalent influenza vaccine (TIV) administered as a single 0.5 mL intramuscular injection in the deltoid muscle. intervention 2: Two doses of inactivated influenza H1N1 vaccine, 15 mcg per dose, administered as a single 0.5 milliliters (mL) intramuscular injection in the deltoid muscle. intervention 3: Normal saline (placebo control) administered as a single 0.5 mL intramuscular injection in the deltoid muscle.

Protocol documents: