Clinical trial NCT00978120: Safety and Efficacy of an H1N1 Influenza Vaccine in People With Asthma
Official title: A Phase II Study in Patients With Asthma to Assess the Safety and Immunogenicity of an Unadjuvanted Novartis H1N1 Influenza Vaccine Administered at Two Dose Levels
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: H1N1 Influenza Virus
Keywords: Influenza A Virus, H1N1 Subtype
Vaccine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2009-09-16
Enrollment: 390
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
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 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.

Detailed description: A new swine-origin influenza A/H1N1 virus was recently identified as a significant cause of respiratory illness in Mexico and the United States. In response, the World Health Organization (WHO) declared a pandemic on June 11, 2009. Current data indicates that licensed seasonal influenza vaccines are not likely to provide protection against the new H1N1 virus. Development and deployment of a vaccine for the new H1N1 virus, particularly to at-risk populations, is essential.

Groups at risk for influenza yearly include the elderly and those with asthma, and current guidelines from the Advisory Committee on Immunization Practices (ACIP) recommend vaccination of adults and children with asthma. Early, unpublished data on US patients hospitalized by H1N1 infection indicates that many had underlying asthma, and it is expected people with asthma will be on a priority list for H1N1 influenza vaccination. Data also indicate that increased dosage of vaccines may increase development of antibodies and that use of certain inhalers may affect immunization. This study will test the safety and immunogenicity of an unadjuvanted, inactivated H1N1 vaccine at two dosage levels in people with asthma.

Participation in this study will last approximately 34 weeks. Participants will be stratified into two groups: those with mild to moderate versus those with severe asthma. All participants will be randomly assigned to receive either a high dose (30 mcg) or low dose (15 mcg) H1N1 vaccine. Both vaccine dosages will be administered in two intramuscular injections 21 days apart. Participants assigned to the higher dose (30 mcg) will receive two injections of the 15 mcg vaccine at each administration.

Participants will complete study visits at entry, administration of the vaccines on Days 1 and 21, follow-ups a week after each vaccine injection, and 21 days after the second injection. Measurements at these visits will include spirometry (measurement of air entering and leaving the lungs), a questionnaire about asthma, a targeted physical examination, an adverse event and medication assessment, inspection of vaccination site, and collection of a blood sample. A urine sample will be collected for pregnancy test before each vaccination. In additions, for 8 days after each vaccination injection participants will keep a diary recording oral temperature, adverse events, asthma symptoms, and use of inhalers. These diaries will be reviewed at study visits. Participants will also receive follow-up phone calls to assess safety 60, 120, and 180 days after the last vaccine injection.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* Has a chronic neurologic or autoimmune disorder
* Has a history of Guillain-Barré Syndrome
* Has an acute or chronic medical condition that, in the opinion of the investigator, would render vaccination unsafe, or would interfere with the evaluation of vaccine response
* Has an ongoing asthma exacerbation or had an asthma exacerbation that was resolved less than 7 days prior to vaccination
* Has any condition that would, in the opinion of the site investigator, place the participant at an unacceptable risk of injury, render the participant unable to meet the requirements of the protocol, or interfere with the successful completion of the study.
* Participated in a novel influenza H1N1 2009 vaccine study in the past two years or has a history of novel influenza H1N1 2009 infection or treatment
* Has known active HIV, Hepatitis B or Hepatitis C infection
* Has a history of alcohol or drug abuse in the last 5 years
* Plans to travel outside of North America in the time between the first vaccination and 42 days following the first vaccination
* Does not speak English primarily

Primary outcomes:
measure: Percentage of Participants With Serious Adverse Events (SAEs) Attributed To Vaccination
timeFrame: Measured at Baseline Visit and Days 1, 8, 21, 28, 41, 80, 120, and 201
measure: Percentage of Participants With Reactogenicity Adverse Events (AEs) Status Post Vaccine 1
timeFrame: Days 1 through 8
measure: Percentage of Participants With Reactogenicity Adverse Events (AEs) Status Post Vaccine 2
timeFrame: Days 21 through 28
measure: Percentage of Participants With Asthma Exacerbations Status Post Vaccine 1
timeFrame: Days 1 to 8
measure: Percentage of Participants With Asthma Exacerbations Status Post Vaccination 2
timeFrame: Days 21 to 28
measure: Percentage of Participants With Seroconversion at Day 28 Following Two Administrations of Vaccination, Mild-Moderate Asthmatics
timeFrame: Days 1 to 28
measure: Percentage of Participants With Seroconversion at Day 28 Following Two Administrations of Vaccination, Severe Asthmatics
timeFrame: Days 1 to 28
measure: Percentage of Participants With Seroconversion at Day 41 Following Two Administrations of Vaccination, Mild-Moderate Asthmatics
timeFrame: Days 1 to 41
measure: Percentage of Participants With Seroconversion at Day 41 Following Two Administrations of Vaccination, Severe Asthmatics
timeFrame: Days 1 to 41
measure: Percentage of Participants With Seroprotection at Day 28 Following Two Administrations of Vaccination, Mild-Moderate Asthmatics
timeFrame: Days 1 to 28
measure: Percentage of Participants With Seroprotection at Day 28 Following Two Administrations of Vaccination, Severe Asthmatics
timeFrame: Days 1 to 28
measure: Percentage of Participants With Seroprotection at Day 41 Following Two Administrations of Vaccination, Mild-Moderate Asthmatics
timeFrame: Days 1 to 41
measure: Percentage of Participants With Seroprotection at Day 41 Following Two Administrations of Vaccination, Severe Asthmatics
timeFrame: Days 1 to 41
Secondary outcomes:
measure: Percentage of Participants With Seroconversion at Day 21 Following Single Administration of Vaccination, Mild-Moderate Asthmatics
timeFrame: Days 1 to 21
measure: Percentage of Participants With Seroconversion at Day 21 Following Single Administration of Vaccination, Severe Asthmatics
timeFrame: Days 1 to 21
measure: Percentage of Participants With Seroprotection at Day 21 Following Single Administration of Vaccination, Mild-Moderate Asthmatics
timeFrame: Days 1 to 21
measure: Percentage of Participants With Seroprotection at Day 21 Following Single Administration of Vaccination, Severe Asthmatics
timeFrame: Days 1 to 21
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Asthma Institute
state: Pennsylvania
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Wisconsin Medical School
name: William Busse, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.