Clinical trial NCT00944073: Peds Sanofi H1N1 Influenza Vaccine Administered at Two Dose Levels
Official title: A Phase II Study in Infants (Greater Than or Equal to 6 - Less Than 36 Months), Children (Greater Than or Equal to 36 Months - 9 Years) and Adolescents (10 - 17 Years) to Assess the Safety and Immunogenicity of an Unadjuvanted Sanofi Pasteur H1N1 Influenza Vaccine Administered at Two Dose Levels
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza
Keywords: H1N1, influenza A viruses, vaccine, infants, children
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2009-07-22
Enrollment: 583
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the safety and the body's immune response (body's defense against disease) to an experimental H1N1 influenza vaccine. Up to 650 healthy volunteers from three age groups (greater than or equal to 6 months to less than 36 months, greater than or equal to 36 months to 9 years, and 10 - 17 years) with no history of influenza H1N1 2009 influenza infection or influenza H1N1 2009 vaccination will participate. Participants will be randomly (by chance) assigned to 1 of 2 possible H1N1 vaccine groups. Group 1 will receive 15 mcg of vaccine; Group 2 will receive 30 mcg of vaccine. Participants will receive vaccine injections on Days 0 and 21 in the arm or thigh muscle. Study procedures include: medical history, physical exam, maintaining a memory aid, and blood sample collection. Participants will be involved in study related procedures for approximately 7 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. Based on clinical data from other novel influenza A viruses, a higher dose, or multiple doses of an unadjuvanted, inactivated influenza H1N1 vaccine may be necessary to confer protection to a maximal number of vaccine recipients. This protocol explores the antibody response following vaccination at 2 different dosage levels (15 mcg and 30 mcg) in up to 650 children aged 6 months to 17 years, inclusive. This study assesses the immune response following a single dose of vaccine, to assess whether individuals have any pre-existing 'prime' immunity, such that the initial H1N1 vaccination serves as a boost, thus conferring a more rapid time to protection and the need for fewer doses. Antibody responses will be assessed after a second dose. This is a randomized, double-blinded, Phase II study in healthy infants, toddlers, children, and adolescents and is designed to investigate the safety, reactogenicity, and immunogenicity of an inactivated influenza H1N1 virus vaccine. The primary objectives are safety, to assess the safety of the unadjuvanted, inactivated influenza H1N1 vaccine when administered at the 15 mcg or 30 mcg dose; and immunogenicity, to assess the antibody response following a single dose of unadjuvanted, inactivated influenza H1N1 vaccine, stratified by age of recipient, when administered at the 15 mcg or 30 mcg dose. The secondary immunogenicity objective is to assess the antibody response following two doses of unadjuvanted, inactivated influenza H1N1 vaccine, stratified by age of recipient, when administered at the 15 mcg or 30 mcg dose. There will be 3 age strata, each containing 200 subjects: greater than or equal to 6 months to less than 36 months, greater than or equal to 36 months to 9 years, and 10 - 17 years . Subjects will be randomized into 2 groups, with 300 subjects per group (100 per strata), to receive intramuscular inactivated influenza H1N1 vaccine at 15 mcg (Group 1) or 30 mcg (Group 2). The vaccine will be administered on Days 0 and 21. Following immunization, safety will be measured by assessment of adverse events (AEs) for 21 days following the last vaccination (Day 42 for those receiving both doses and Day 21 for those who do not receive the second dose); serious adverse events (SAEs) and new-onset chronic medical conditions through 7 months post first vaccination (Day 201); and reactogenicity to the vaccines for 8 days following each vaccination (Day 0-7). Immunogenicity testing will include HAI and neutralizing antibody testing on serum obtained on the day of each vaccination (prior to vaccination) and 21 days following the second vaccination (Day 42). For subjects aged 10-17 years, serum for antibody assays will also be obtained at Day 8-10 following each vaccination. However, for the greater than or equal to 6 months - less than 36 months and the greater than o

Eligibility criteria: Inclusion Criteria:

* Are males or non-pregnant females aged 6 months to 17 years, inclusive.
* Subjects of child-bearing potential must agree to practice adequate contraception that may include, but is not limited to, abstinence, barrier methods such as condoms, diaphragms, spermicides, intrauterine devices, and licensed hormonal methods during the study for at least 30 days following the last vaccination.
* The subject must be in good health as determined by axillary (\<10 years of age) or oral temperature (axillary temperature \<100 degrees Fahrenheit or oral temperature \<101 degrees Fahrenheit), medical history, and targeted physical examination based on medical history.
* Subject and/or parent(s)/legal guardian(s) must be willing and able to comply with planned study procedures and be available for all study visits.
* Subject and/or parent(s) legal guardian(s) must provide written informed consent prior to initiation of any study procedures, and subject may provide written assent as appropriate.

Exclusion Criteria:

* Have a known allergy to eggs or other components of the vaccine (including gelatin, formaldehyde, octoxinol, thimerosal and chicken protein).
* Have a positive urine or serum pregnancy test within 24 hours prior to vaccination or are breastfeeding.
* Have immunosuppression as a result of an underlying illness or treatment, or use of anticancer chemotherapy or radiation therapy (cytotoxic) within the preceding 36 months.
* Have an active neoplastic disease or a history of any hematologic malignancy.
* Have long term use of glucocorticoids including oral, parenteral or high-dose inhaled steroids (\>800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months. (Nasal and topical steroids are allowed.)
* Have a diagnosis of schizophrenia, bipolar disease, or other major psychiatric diagnosis including major depression.
* Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others.
* Are receiving any psychiatric drugs (aripiprazole, clozapine, ziprasidone, haloperidol, molindone, loxapine, thioridazine, thiothixene, pimozide, fluphenazine, risperidone, mesoridazine, quetiapine, trifluoperazine, chlorprothixene, chlorpromazine, perphenazine, trifluopromazine, olanzapine, carbamazepine, divalproex sodium, lithium carbonate or lithium citrate) or any drugs for treatment of depression.
* Have a history of receiving immunoglobulin or other blood product within the 3 months prior to vaccination in this study.
* Received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 1 month prior to vaccination in this study or expect to receive an experimental agent during this study (prior to the Day 201 follow-up call - 180 days after the second vaccination).
* Have received any live licensed vaccines within 4 weeks or inactivated licensed vaccines within 2 weeks prior to vaccination in this study or plan receipt of such vaccines within 21 days following the second vaccination. This is inclusive of routine childhood immunizations provided outside the scope of this study, and seasonal influenza vaccines. The initiation of this protocol does not take precedence over routine immunizations.
* Have an acute or chronic medical condition that, in the opinion of the investigator, would render vaccination unsafe, or would interfere with the evaluation of responses.
* Have a history of severe reactions following previous immunization with influenza virus vaccines.
* Have an acute illness, including an axillary temperature greater than 100 degrees Fahrenheit or an oral temperature greater than or equal to 101 degrees Fahrenheit, within 3 days prior to vaccination.
* Have any condition that would, in the opinion of the site investigator, place them at an unacceptable risk of injury or render them unable to meet the requirements of the protocol.
* Participated in a novel influenza H1N1 2009 vaccine study in the past two years or have a history of novel influenza H1N1 2009 infection prior to enrollment.
* Have known active human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection.
* Have a history of alcohol or drug abuse.
* Plan to travel outside of North America in the time between the first vaccination and 42 days following the first vaccination.
* Have a history of Guillain-Barré Syndrome.
* Have any condition that the investigator believes may interfere with successful completion of the study.

Primary outcomes:
measure: Number of Participants Reporting Solicited Subjective Local Reactions After the First Vaccination
timeFrame: Day 0-7 after first vaccination
measure: Number of Participants Reporting Solicited Subjective Local Reactions After the Second Vaccination
timeFrame: Day 0-7 after second vaccination
measure: Number of Participants Reporting Solicited Quantitative Local Reactions After the First Vaccination
timeFrame: Day 0-7 after first vaccination
measure: Number of Participants Reporting Solicited Quantitative Local Reactions After the Second Vaccination
timeFrame: Day 0-7 after second vaccination
measure: Number of Participants Reporting Solicited Quantitative Systemic Reactions After the First Vaccination
timeFrame: Day 0-7 after first vaccination
measure: Number of Participants Reporting Solicited Quantitative Systemic Reactions After the Second Vaccination
timeFrame: Day 0-7 after second vaccination
measure: Number of Participants Age 6 to Less Than 36 Months Reporting Solicited Subjective Systemic Reactions After the First Vaccination
timeFrame: Day 0-7 after first vaccination
measure: Number of Participants Age 6 to Less Than 36 Months Reporting Solicited Subjective Systemic Reactions After the Second Vaccination
timeFrame: Day 0-7 after second vaccination
measure: Number of Participants Age 36 Months to 9 Years Reporting Solicited Subjective Systemic Reactions After the First Vaccination
timeFrame: Day 0-7 after first vaccination
measure: Number of Participants Age 36 Months to 9 Years Reporting Solicited Subjective Systemic Reactions After the Second Vaccination
timeFrame: Day 0-7 after second vaccination
measure: Number of Participants Age 10 to 17 Years Reporting Solicited Subjective Systemic Reactions After the First Vaccination
timeFrame: Day 0-7 after first vaccination
measure: Number of Participants Age 10 to 17 Years Reporting Solicited Subjective Systemic Reactions After the Second Vaccination
timeFrame: Day 0-7 after second vaccination
measure: Number of Participants Reporting Vaccine-associated Serious Adverse Events (SAEs)
timeFrame: Day 0 through Day 180 after last vaccination
measure: Number of Participants Age 6 to Less Than 36 Months With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the Influenza H1N1 2009 Virus at Day 0
timeFrame: Day 0
measure: Number of Participants Age 6 to Less Than 36 Months With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the Influenza H1N1 2009 Virus at Day 8-10 Following a Single Dose of H1N1 Vaccine
timeFrame: Day 8-10
measure: Number of Participants Age 6 to Less Than 36 Months With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the Influenza H1N1 2009 Virus at Day 21 Following a Single Dose of H1N1 Vaccine
timeFrame: Day 21
measure: Number of Participants Age 36 Months to 9 Years With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the Influenza H1N1 2009 Virus at Day 0
timeFrame: Day 0
measure: Number of Participants Age 36 Months to 9 Years With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the Influenza H1N1 2009 Virus at Day 8-10 Following a Single Dose of H1N1 Vaccine
timeFrame: Day 8-10
measure: Number of Participants Age 36 Months to 9 Years Years With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the Influenza H1N1 2009 Virus at Day 21 Following a Single Dose of H1N1 Vaccine
timeFrame: Day 21
measure: Number of Participants Age 10 to 17 Years With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the Influenza H1N1 2009 Virus at Day 0 and at Days 8-10 and 21 Following a Single Dose of H1N1 Vaccine
timeFrame: Day 0 prior to vaccination and Days 8-10 and 21 after first vaccination
measure: Number of Participants Age 6 to Less Than 36 Months With 4-Fold or Greater HAI Antibody Titer Increases Against the Influenza H1N1 2009 Virus at Day 8-10 Following a Single Dose of H1N1 Vaccine
timeFrame: Day 0 prior to and Day 8-10 after first vaccination
measure: Number of Participants Age 6 to Less Than 36 Months With 4-Fold or Greater HAI Antibody Titer Increases Against the Influenza H1N1 2009 Virus at Day 21 Following a Single Dose of H1N1 Vaccine
timeFrame: Day 0 prior to and Day 21 after first vaccination
measure: Number of Participants Age 36 Months to 9 Years With 4-Fold or Greater HAI Antibody Titer Increases Against the Influenza H1N1 2009 Virus at Day 8-10 Following a Single Dose of H1N1 Vaccine
timeFrame: Day 0 prior to and Day 8-10 after first vaccination
measure: Number of Participants Age 36 Months to 9 Years With 4-Fold or Greater HAI Antibody Titer Increases Against the Influenza H1N1 2009 Virus at Day 21 Following a Single Dose of H1N1 Vaccine
timeFrame: Day 0 prior to and Day 21 after first vaccination
measure: Number of Participants Age 10 to 17 Years With 4-Fold or Greater HAI Antibody Titer Increases Against the Influenza H1N1 2009 Virus at Days 8-10 and 21 Following a Single Dose of H1N1 Vaccine
timeFrame: Day 0 prior to and Days 8-10 and 21 after first vaccination
Secondary outcomes:
measure: Number of Participants Age 6 to Less Than 36 Months With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the Influenza H1N1 2009 Virus at Day 8-10 Following the Second Dose of H1N1 Vaccine
timeFrame: Day 8-10 after the second vaccination
measure: Number of Participants Age 6 to Less Than 36 Months With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the Influenza H1N1 2009 Virus Day 21 Following the Second Dose of H1N1 Vaccine
timeFrame: Day 21 after the second vaccination
measure: Number of Participants Age 36 Months to 9 Years With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the Influenza H1N1 2009 Virus at Day 8-10 Following the Second Dose of H1N1 Vaccine
timeFrame: Day 8-10 after the second vaccination
measure: Number of Participants Age 36 Months to 9 Years With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the Influenza H1N1 2009 Virus at Day 21 Following the Second Dose of H1N1 Vaccine
timeFrame: Day 21 after the second vaccination
measure: Number of Participants Age 10 to 17 Years With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the Influenza H1N1 2009 Virus at Day 8-10 Following the Second Dose of H1N1 Vaccine
timeFrame: Day 8-10 after the second vaccination
measure: Number of Participants Age 10 to 17 Years With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the Influenza H1N1 2009 Virus at Day 21 Following the Second Dose of H1N1 Vaccine
timeFrame: Day 21 after the second vaccination
measure: Number of Participants Age 6 to Less Than 36 Months With 4-Fold or Greater HAI Antibody Titer Increases Against the Influenza H1N1 2009 Virus at Day 8-10 Following the Second Dose of H1N1 Vaccine
timeFrame: Day 0 prior to first vaccination and Day 8-10 after the second vaccination
measure: Number of Participants Age 6 to Less Than 36 Months With 4-Fold or Greater HAI Antibody Titer Increases Against the Influenza H1N1 2009 Virus at Day 21 Following the Second Dose of H1N1 Vaccine
timeFrame: Day 0 prior to first vaccination and Day 21 after the second vaccination
measure: Number of Participants Age 36 Months to 9 Years With 4-Fold or Greater HAI Antibody Titer Increases Against the Influenza H1N1 2009 Virus at Day 8-10 Following the Second Dose of H1N1 Vaccine
timeFrame: Day 0 prior to first vaccination and Day 8-10 after the second vaccination
measure: Number of Participants Age 36 Months to 9 Years With 4-Fold or Greater HAI Antibody Titer Increases Against the Influenza H1N1 2009 Virus at Day 21 Following the Second Dose of H1N1 Vaccine
timeFrame: Day 0 prior to first vaccination and Day 21 after the second vaccination
measure: Number of Participants Age 10 to 17 Years With 4-Fold or Greater HAI Antibody Titer Increases Against the Influenza H1N1 2009 Virus at Day 8-10 Following the Second Dose of H1N1 Vaccine
timeFrame: Day 0 prior to first vaccination and Day 8-10 after the second vaccination
measure: Number of Participants Age 10 to 17 Years With 4-Fold or Greater HAI Antibody Titer Increases Against the Influenza H1N1 2009 Virus at Day 21 Following the Second Dose of H1N1 Vaccine
timeFrame: Day 0 prior to first vaccination and Day 21 after the second vaccination
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland School of Medicine - Center for Vaccine Development - Baltimore
state: Maryland
city: Kansas City
country: United States
facility: Children's Mercy Hospital and Clinics - Infectious Diseases
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis University - Center for Vaccine Development
state: Missouri
city: Durham
country: United States
facility: Duke Translational Medicine Institute - Clinical Vaccine Unit
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center - Infectious Diseases
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center
state: Tennessee
city: Galveston
country: United States
facility: University of Texas Medical Branch - Pediatrics - Infectious Diseases and Immunology - Galveston
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine - Molecular Virology and Microbiology
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital - Infectious Diseases
state: Washington
Study officials:
References:
citation: Kotloff KL, Halasa NB, Harrison CJ, Englund JA, Walter EB, King JC, Creech CB, Healy SA, Dolor RJ, Stephens I, Edwards KM, Noah DL, Hill H, Wolff M. Clinical and immune responses to inactivated influenza A(H1N1)pdm09 vaccine in children. Pediatr Infect Dis J. 2014 Aug;33(8):865-71. doi: 10.1097/INF.0000000000000329.