Safety and Efficacy of an H1N1 Influenza Vaccine in People With Asthma

NCT00978120 | Completed Phase 2 Results

• 1 other identifier: DAIT-AAIB-flu-001
• Study Type: interventional
• Target: 390
• Locations: 1 country
• Sites: 7

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 in people with asthma. The study will enroll 350, and possibly up to 400 healthy adults ages 12 and older with mild, moderate, or severe asthma. Participants will be randomly assigned to 1 of 2 possible vaccine groups: group 1 will receive 15 mcg of H1N1 vaccine; group 2 will receive 30 mcg of H1N1 vaccine given as two 15 mcg injections. Both groups will receive vaccine injections on days 0 and 21. Study procedures include: medical history, physical exam, spirometry, maintaining a memory aid and, and blood sample collection. Participants will be involved in study related procedures for approximately 7 months.

Conditions

H1N1 Influenza Virus

Keywords

Influenza A Virus, H1N1 Subtype; Vaccine

Outcome Measures

Primary Outcomes (13)

• Percentage of Participants With Serious Adverse Events (SAEs) Attributed To Vaccination

  Percentage of participants with serious adverse events (SAEs) attributed to vaccination, as determined by site investigators at the time of reporting.

  Measured at Baseline Visit and Days 1, 8, 21, 28, 41, 80, 120, and 201

• Percentage of Participants With Reactogenicity Adverse Events (AEs) Status Post Vaccine 1

  Percentage of participants with reactogenicity AEs, local (erythema, ecchymosis, induration, pain and tenderness at the injection sites) and systemic (feverishness, chills, fatigue, myalgias, arthralgias, headache and nausea), within 8 Days After Vaccination 1 by Dose Level Group.

  Days 1 through 8

• Percentage of Participants With Reactogenicity Adverse Events (AEs) Status Post Vaccine 2

  Percentage of participants with reactogenicity AEs, local (erythema, ecchymosis, induration, pain and tenderness at the injection sites) and systemic (feverishness, chills, fatigue, myalgias, arthralgias, headache and nausea), within 8 Days After Vaccination 2 by Dose Level Group.

  Days 21 through 28

• Percentage of Participants With Asthma Exacerbations Status Post Vaccine 1

  Percentage of participants with asthma exacerbations within 8 days after vaccination 1. Any of the following events are considered asthma exacerbation: Increase in the daily use of bronchodilator rescue medication for 2 consecutive days; an increase is defined as ≥6puffs of bronchodilator from a metered-dose inhaler or ≥2 uses of nebulized albuterol above average use reported in the two weeks prior to Visit 1. Increase in use of systemic corticosteroids or the addition of systemic corticosteroids to treatment regimen for asthma. Unscheduled use of health care for the treatment of asthma.

  Days 1 to 8

• Percentage of Participants With Asthma Exacerbations Status Post Vaccination 2

  Percentage of participants with asthma exacerbations within 8 days after vaccination 2. Any of the following events are considered asthma exacerbation: Increase in the daily use of bronchodilator rescue medication for 2 consecutive days; an increase is defined as ≥6puffs of bronchodilator from a metered-dose inhaler or ≥2 uses of nebulized albuterol above average use reported in the two weeks prior to Visit 1. Increase in use of systemic corticosteroids or the addition of systemic corticosteroids to treatment regimen for asthma. Unscheduled use of health care for the treatment of asthma.

  Days 21 to 28

• Percentage of Participants With Seroconversion at Day 28 Following Two Administrations of Vaccination, Mild-Moderate Asthmatics

  Seroconversion: The percentage of participants with a four-fold or greater hemagglutination inhibition assay (HAI) antibody titer increase compared to baseline against the novel influenza hemagglutinin type 1 and neuraminidase type 1 (H1N1) 2009 virus following two administrations of Novartis H1N1 vaccine at each dose, combined across age groups.

  Days 1 to 28

• Percentage of Participants With Seroconversion at Day 28 Following Two Administrations of Vaccination, Severe Asthmatics

  Seroconversion: The percentage of participants with a four-fold or greater hemagglutination inhibition assay (HAI) antibody titer increase compared to baseline against the novel influenza hemagglutinin type 1 and neuraminidase type 1 (H1N1) 2009 virus following two administrations of Novartis H1N1 vaccine at each dose, combined across age groups.

  Days 1 to 28

• Percentage of Participants With Seroconversion at Day 41 Following Two Administrations of Vaccination, Mild-Moderate Asthmatics

  Seroconversion: The percentage of participants with a four-fold or greater hemagglutination inhibition assay (HAI) antibody titer increase compared to baseline against the novel influenza hemagglutinin type 1 and neuraminidase type 1 (H1N1) 2009 virus following two administrations of Novartis H1N1 vaccine at each dose, combined across age groups.

  Days 1 to 41

• Percentage of Participants With Seroconversion at Day 41 Following Two Administrations of Vaccination, Severe Asthmatics

  Seroconversion: The percentage of participants with a four-fold or greater hemagglutination inhibition assay (HAI) antibody titer increase compared to baseline against the novel influenza hemagglutinin type 1 and neuraminidase type 1 (H1N1) 2009 virus following two administrations of Novartis H1N1 vaccine at each dose, combined across age groups.

  Days 1 to 41

• Percentage of Participants With Seroprotection at Day 28 Following Two Administrations of Vaccination, Mild-Moderate Asthmatics

  Seroprotection: The percentage of participants with a hemagglutination inhibition assay (HAI) antibody titer of 1:40 or greater against influenza H1N1 2009 virus following two administrations of the H1N1 vaccine at each dose, combined across age groups.

  Days 1 to 28

• Percentage of Participants With Seroprotection at Day 28 Following Two Administrations of Vaccination, Severe Asthmatics

  Percentage of participants with seroprotection defined as a hemagglutination inhibition assay (HAI) antibody titer of 1:40 or greater against influenza H1N1 2009 virus following two administrations of the H1N1 vaccine at each dose, combined across age groups.

  Days 1 to 28

• Percentage of Participants With Seroprotection at Day 41 Following Two Administrations of Vaccination, Mild-Moderate Asthmatics

  Percentage of participants with seroprotection defined as a hemagglutination inhibition assay (HAI) antibody titer of 1:40 or greater against influenza H1N1 2009 virus following two administrations of the H1N1 vaccine at each dose, combined across age groups.

  Days 1 to 41

• Percentage of Participants With Seroprotection at Day 41 Following Two Administrations of Vaccination, Severe Asthmatics

  Percentage of participants with seroprotection defined as a hemagglutination inhibition assay (HAI) antibody titer of 1:40 or greater against influenza H1N1 2009 virus following two administrations of the H1N1 vaccine at each dose, combined across age groups.

  Days 1 to 41

Secondary Outcomes (4)

• Percentage of Participants With Seroconversion at Day 21 Following Single Administration of Vaccination, Mild-Moderate Asthmatics

  Days 1 to 21

• Percentage of Participants With Seroconversion at Day 21 Following Single Administration of Vaccination, Severe Asthmatics

  Days 1 to 21

• Percentage of Participants With Seroprotection at Day 21 Following Single Administration of Vaccination, Mild-Moderate Asthmatics

  Days 1 to 21

• Percentage of Participants With Seroprotection at Day 21 Following Single Administration of Vaccination, Severe Asthmatics

  Days 1 to 21

Study Arms (2)

H1N1 vaccine high dose

EXPERIMENTAL

Participants will be stratified according to asthma severity and will receive the high dosage of the H1N1 vaccine.

Biological: H1N1 vaccine high dose

H1N1 vaccine low dose

EXPERIMENTAL

Participants will be stratified according to asthma severity and will receive the low dosage of the H1N1 vaccine.

Biological: H1N1 vaccine low dose

Interventions

H1N1 vaccine high dose BIOLOGICAL

30 mcg of unadjuvanted Novartis H1N1 vaccine delivered as two, 15 micrograms (mcg), intramuscular injections. Each 30 mcg dose is administered 21 days apart.

H1N1 vaccine high dose

H1N1 vaccine low dose BIOLOGICAL

15 mcg of unadjuvanted Novartis H1N1 vaccine delivered in two intramuscular injections 21 days apart

H1N1 vaccine low dose

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of mild/moderate or severe asthma according to Severe Asthma Research Project (SARP) definitions and either a SARP participant or having prior participation in the studies or clinics of the investigators
• Males and females age 12 (inclusive) and older
• Females of child-bearing potential must not be pregnant and must agree to practice adequate contraception that may include, but is not limited to: abstinence, monogamous relationship with vasectomized partner, 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.
• Able to understand and comply with planned study procedures
• Will provide written informed consent and assent (if age appropriate) prior to initiation of any study procedures

You may not qualify if:

• Allergy to eggs or other components of the vaccine, including gelatin, formaldehyde, octoxinol, thimerosal, and chicken protein
• Positive urine pregnancy test within 24 hours prior to vaccination, if a female of childbearing potential
• Currently breastfeeding
• History of smoking 20 pack-years or greater (current or former smokers with a history of less than 20 pack-years can be included in the study)
• Has been previously diagnosed by a physician with chronic obstructive pulmonary disease, chronic bronchitis, emphysema, or cystic fibrosis
• Has received anticancer chemotherapy or radiation therapy (cytotoxic) within the past 36 months
• Has an active neoplastic disease or a history of any hematologic malignancy
• Has a diagnosis of schizophrenia, bipolar disease, or other major psychiatric diagnosis
• Has been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within the past 10 years
• Receiving psychiatric drugs (subjects who are receiving a single antidepressant drug and are stable for at least 3 months prior to study entry, without de-compensating symptoms, will be allowed to enroll)
• History of receiving immunoglobulin, including anti-cytokine antibodies, or other blood product within the 3 months prior to vaccination in this study
• Has 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 141 follow-up call - 100 days after the second vaccination)
• Has 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
• Has a history of severe reactions following previous immunization with influenza virus vaccines
• Has an acute illness, including an oral temperature greater than 100.4°F, within 1 week of either vaccination

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (7)

Emory University

Atlanta, Georgia, United States

Location

Washington University School of Medicine

St Louis, Missouri, United States

Location

Wake Forest University School of Medicine

Winston-Salem, North Carolina, United States

Location

Cleveland Clinic

Cleveland, Ohio, United States

Location

University of Pittsburgh Asthma Institute

Pittsburgh, Pennsylvania, United States

Location

University of Virginia

Charlottesville, Virginia, United States

Location

University of Wisconsin

Madison, Wisconsin, United States

Location

Related Publications (4)

• Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team; Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, Garten RJ, Gubareva LV, Xu X, Bridges CB, Uyeki TM. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med. 2009 Jun 18;360(25):2605-15. doi: 10.1056/NEJMoa0903810. Epub 2009 May 7.

  PMID: 19423869 BACKGROUND

• Patriarca PA, Cox NJ. Influenza pandemic preparedness plan for the United States. J Infect Dis. 1997 Aug;176 Suppl 1:S4-7. doi: 10.1086/514174.

  PMID: 9240686 BACKGROUND

• Proceedings of the ATS workshop on refractory asthma: current understanding, recommendations, and unanswered questions. American Thoracic Society. Am J Respir Crit Care Med. 2000 Dec;162(6):2341-51. doi: 10.1164/ajrccm.162.6.ats9-00. No abstract available.

  PMID: 11112161 BACKGROUND

• Busse WW, Peters SP, Fenton MJ, Mitchell H, Bleecker ER, Castro M, Wenzel S, Erzurum SC, Fitzpatrick AM, Teague WG, Jarjour N, Moore WC, Sumino K, Simeone S, Ratanamaneechat S, Penugonda M, Gaston B, Ross TM, Sigelman S, Schiepan JR, Zaccaro DJ, Crevar CJ, Carter DM, Togias A. Vaccination of patients with mild and severe asthma with a 2009 pandemic H1N1 influenza virus vaccine. J Allergy Clin Immunol. 2011 Jan;127(1):130-7, 137.e1-3. doi: 10.1016/j.jaci.2010.11.014. Epub 2010 Dec 9.

  PMID: 21145578 RESULT

Results Point of Contact

• Title: Associate Director, Clinical Research Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• William Busse, MD

  University of Wisconsin Medical School

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2009
• First Posted: September 16, 2009
• Study Start: October 1, 2009
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: August 10, 2012
• Results First Posted: August 6, 2012

Record last verified: 2012-08

Locations

US (7)