A Study of Different Formulations of an A/H1N1 Pandemic Vaccine in Healthy Children Aged 6 Months to 9 Years

Immunogenicity and Safety of Multiple Formulations of an A/H1N1 Pandemic Vaccine in Healthy Subjects Aged 6 Months to 9 Years

The purpose of the study is to evaluate different doses of the Influenza A/H1N1 pandemic vaccine in toddlers and children.

Primary Objectives:

• To describe the immunogenicity of the candidate vaccines after each injection.
• To describe the safety of the candidate vaccines after each injection.

Study Overview

• Status: Completed
• Conditions: Influenza; Swine-origin A/H1N1 Influenza
• Intervention / Treatment: Biological: Monovalent Subvirion A/H1N1 Influenza vaccine; Biological: Monovalent Subvirion A/H1N1 Influenza vaccine; Biological: Normal saline solution (placebo)

Detailed Description

Participants will receive two injections of their randomized vaccine on Day 0 and Day 21, respectively.

• Study Type: Interventional
• Enrollment (Actual): 474
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami Beach, Florida, United States, 33141
  • Georgia
    • Marietta, Georgia, United States, 30062
    • Woodstock, Georgia, United States, 30189
  • Kentucky
    • Crestview Hills, Kentucky, United States, 41017
    • Louisville, Kentucky, United States, 40291
    • Maddisonville, Kentucky, United States, 42431
  • Louisiana
    • Metairie, Louisiana, United States, 70006
  • Nevada
    • Las Vegas, Nevada, United States, 89104
  • New York
    • Rochester, New York, United States, 14609
  • Pennsylvania
    • Hermitage, Pennsylvania, United States, 16148
    • Pittsburgh, Pennsylvania, United States, 15237
    • Pittsburgh, Pennsylvania, United States, 15241
  • Rhode Island
    • Cranston, Rhode Island, United States, O2920
  • South Carolina
    • Barnwell, South Carolina, United States, 29812
  • Texas
    • Austin, Texas, United States, 78705
    • Fort Worth, Texas, United States, 76135
    • San Angelo, Texas, United States, 76904
  • Utah
    • Orem, Utah, United States, 84057
    • South Jordan, Utah, United States, 84095
    • Springville, Utah, United States, 84663

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 9 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria :

All subjects:

• Provision of Informed Consent Form signed by the subject's parent(s)/legal representative (and by an independent witness if required by local regulations). In addition, provision of Assent Form signed by subjects aged 7 to 9 years
• Subject and parent/guardian are able to attend all scheduled visits and to comply with all trial procedures

Subjects aged 3 to 9 years:

• Healthy children aged 3 to 9 years on the day of inclusion

Subjects aged 6 to 35 months:

• Healthy infants and toddlers aged 6 to 35 months on the day of inclusion
• Born at full term of pregnancy (≥ 37 weeks) and with a birth weight ≥ 2.5 kg

Exclusion Criteria :

• Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination
• Planned participation in another clinical trial during the present trial period
• Receipt of any vaccine in the 4 weeks preceding the trial vaccination
• Planned receipt of any vaccine prior to the Day 42 blood sample
• Receipt of blood or blood-derived products in the past 3 months which might interfere with the assessment of immune response
• Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
• Self-reported seropositivity for Human Immunodeficiency Virus (HIV), Hepatitis B surface antigen, or Hepatitis C
• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances
• Self reported thrombocytopenia contraindicating intramuscular (IM) vaccination
• Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding inclusion contraindicating IM vaccination
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
• Chronic illness that in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion
• Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator.
• Any confirmed case of influenza (including swine-origin A/H1N1 Influenza) since March 2009
• Personal or family history of Guillain-Barré syndrome
• Active neoplastic disease or a history of any hematologic malignancy
• Known seizure/epilepsy history and/or taking anti-seizure medication
• Receipt of psychiatric drugs. Subjects receiving a single antidepressant drug and stable for at least 3 months prior to enrollment, without decompensating symptoms will be allowed to enroll in the study
• Febrile illness (temperature ≥ 100.4°F [≥ 38.0°C]) or moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A/H1N1 Vaccine Group 1; Participants will receive A/H1N1 vaccine formulation 1	Biological: Monovalent Subvirion A/H1N1 Influenza vaccine; 0.5 mL, Intramuscular Day 0 and Day 21 (3 to 9 years); 0.25 mL, Intramuscular on Day 0 and Day 21 (6 months to 35 Months); Biological: Monovalent Subvirion A/H1N1 Influenza vaccine; 0.5 mL, Intramuscular Day 0 and Day 21 (3 to 9 years); 0.25 mL, Intramuscular on day 0 and Day 21 (6 months to 35 Months)
Experimental: A/H1N1 Vaccine Group 2; Participants will receive A/H1N1 vaccine formulation 2	Biological: Monovalent Subvirion A/H1N1 Influenza vaccine; 0.5 mL, Intramuscular Day 0 and Day 21 (3 to 9 years); 0.25 mL, Intramuscular on Day 0 and Day 21 (6 months to 35 Months); Biological: Monovalent Subvirion A/H1N1 Influenza vaccine; 0.5 mL, Intramuscular Day 0 and Day 21 (3 to 9 years); 0.25 mL, Intramuscular on day 0 and Day 21 (6 months to 35 Months)
Placebo Comparator: Placebo Group; Participants will receive a placebo vaccine	Biological: Normal saline solution (placebo); 0.5 mL, Intramuscular Day 0 and Day 21 (3 to 9 years); 0.25 mL, Intramuscular on day 0 and Day 21 (6 months to 35 Months)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Antibody Titers ≥ 10 1/Dilution (1/Dil) Against A/California (H1N1 Vaccine) Strain - Age 6 to 35 Months	Pre- and post-vaccination antibody titers were determined by the hemagglutination inhibition (HAI) test.	Pre-vaccination (Day 0) and 21 days post-vaccination
Number of Participants With Antibody Titers ≥ 40 1/Dilution (1/Dil) Against A/California (H1N1 Vaccine) Strain - Age 6 to 35 Months	Seroprotection: Antibody titer of ≥ 40 1/dil. Antibody titers were determined by the hemagglutination inhibition (HAI) test.	Pre-vaccination (Day 0) and Day 21 post-vaccination
Geometric Mean Titers (GMT) of Antibodies Against A/California (H1N1 Vaccine) Strain - Age 6 to 35 Months	Pre-vaccination and post-vaccination antibody titers were determined by the hemagglutination inhibition (HAI) test.	Pre-vaccination (Day 0) and 21 days post-vaccination
Number of Participants With Antibody Titers ≥ 10 1/Dilution (1/Dil) Against A/California (H1N1 Vaccine) Strain - Age 3 to 9 Years	Pre-vaccination and post-vaccination antibody titers were determined by the hemagglutination inhibition (HAI) test.	Pre-vaccination (Day 0) and 21 days post-vaccination
Number of Participants With Antibody Titers ≥ 40 1/Dilution (1/Dil) Against A/California (H1N1 Vaccine) Strain - Age 3 to 9 Years	Seroprotection: Antibody titer ≥ 40 1/dil. Antibody titers were determined by the hemagglutination inhibition (HAI) test.	Pre-vaccination (Day 0) and Day 21 post-vaccination
Geometric Mean Titers (GMT) of Antibodies Against A/California (H1N1 Vaccine) Strain - Age 3 to 9 Years	Pre-vaccination and post-vaccination antibody titers were determined by the hemagglutination inhibition (HAI) test.	Pre-vaccination (Day 0) and Day 21 post-vaccination
Number of Participants With At Least One Solicited Injection Site or Systemic Reaction Following Vaccination - Age 6 to 23 Months	Solicited Injection Site Reactions: Tenderness, erythema (redness), swelling, induration (hardening), ecchymosis (bruising). Solicited systemic reactions: Fever (temperature), vomiting, crying abnormal, drowsiness, appetite lost, irritability.	Days 0 to 7 post-vaccination
Number of Participants With At Least One Solicited Injection Site or Systemic Reaction Following Vaccination - Age 24 to 35 Months	Solicited Injection Site Reactions: Pain, erythema (redness), swelling, induration (hardening), ecchymosis (bruising). Solicited systemic reactions: Fever (temperature), headache, malaise (feeling unwell), myalgia (muscle aches and pains), shivering.	Days 0 to 7 post-vaccination
Number of Participants With At Least One Solicited Injection Site or Systemic Reaction Following Vaccination - Age 3 to 9 Years	Solicited Injection Site Reactions: Pain, erythema (redness), swelling, induration (hardening), ecchymosis (bruising). Solicited systemic reactions: Fever (temperature), headache, malaise (feeling unwell), myalgia (muscle aches and pains), shivering.	Days 0 to 7 post vaccination

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• Plennevaux E, Blatter M, Cornish MJ, Go K, Kirby D, Wali M, Reeves-Hoche MK, Denis M. Influenza A (H1N1) 2009 two-dose immunization of US children: an observer-blinded, randomized, placebo-controlled trial. Vaccine. 2011 Feb 11;29(8):1569-75. doi: 10.1016/j.vaccine.2010.12.116. Epub 2011 Jan 8.
• Plennevaux E, Sheldon E, Blatter M, Reeves-Hoche MK, Denis M. Immune response after a single vaccination against 2009 influenza A H1N1 in USA: a preliminary report of two randomised controlled phase 2 trials. Lancet. 2010 Jan 2;375(9708):41-8. doi: 10.1016/S0140-6736(09)62026-2. Epub 2009 Dec 15.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: August 3, 2009
• First Submitted That Met QC Criteria: August 4, 2009
• First Posted (Estimate): August 6, 2009

Study Record Updates

• Last Update Posted (Estimate): April 14, 2016
• Last Update Submitted That Met QC Criteria: April 12, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Children; Influenza; Pandemic Flu; Swine-origin A/H1N1 Influenza
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: FUF15; UTN: U1111-1111-4713