Safety and Efficacy of an H1N1 Influenza Vaccine in People With Asthma - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00978120

Purpose

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.

Condition	Intervention	Phase
H1N1 Influenza Virus	Biological: H1N1 vaccine high dose Biological: H1N1 vaccine low dose	Phase II

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
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

Resource links provided by NLM:

MedlinePlus related topics: Asthma Flu

Drug Information available for: Influenza Vaccines

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Occurrence of vaccine-associated serious adverse events (SAEs) throughout the course of the study by dose level group (15 or 30 mcg), by asthma severity group (mild-to-moderate or severe), by dose level group + asthma severity group, and overall [ Time Frame: Measured at baseline and at Days 1, 8, 21, 28, 42, 80, 120, and 201 ] [ Designated as safety issue: Yes ]
Occurrence of solicited local AEs within 8 days after vaccination by dose level group (15 or 30 mcg), asthma severity group (mild/moderate or severe), dose level group + asthma severity group, and overall [ Time Frame: Measured on Days 1 to 8 and 21 to 28 ] [ Designated as safety issue: Yes ]
Occurrence of solicited systemic AEs within 8 days post vaccination by dose level group (15 or 30 mcg), asthma severity group (mild/moderate or severe), dose level group + asthma severity group, and overall [ Time Frame: Measured on Days 1 to 8 and 21 to 28 ] [ Designated as safety issue: Yes ]
Occurrence of asthma exacerbations within 8 days post vaccination by dose level group (15 or 30 mcg), asthma severity group (mild/moderate or severe), dose level group + asthma severity group, and overall [ Time Frame: Measured on Days 1 to 8 and 21 to 28 ] [ Designated as safety issue: Yes ]
Proportion of participants stratified by asthma severity achieving 4-fold or greater HAI antibody titer increases against the novel influenza H1N1 2009 virus following two administrations of Novartis H1N1 vaccine, at each dose, combined across age groups [ Time Frame: Measured on Days 1, 8, 21, 28, and 42 ] [ Designated as safety issue: No ]
Proportion of participants stratified by asthma severity achieving a serum HAI antibody titer of 1:40 or greater against the novel influenza H1N1 2009 virus following two administrations of Novartis H1N1 vaccine at each dose, combined across age groups [ Time Frame: Measured on Days 1, 8, 21, 28, and 42 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Changes in spirometry outcomes (FEV1, FVC, FEV1/FVC) after both the first and the second vaccine administration by dose (15 mcg or 30 mcg), by asthma severity group (mild/moderate or severe), by dose + asthma severity group, and overall [ Time Frame: Measured at baseline and on Days 8, 21, 28, 42 ] [ Designated as safety issue: No ]
Unsolicited AEs by dose level group (15 mcg or 30 mcg), by asthma severity group (mild/moderate or severe), by dose level + asthma severity groups, and overall [ Time Frame: Measured through Day 42 ] [ Designated as safety issue: No ]
Occurrence of asthma exacerbations by dose (15 or 30 mcg), by asthma severity group (mild/moderate or severe), by dose + asthma severity group, and overall [ Time Frame: Measured on Days 1 to 20 and 21 to 42 ] [ Designated as safety issue: No ]
Proportion of participants stratified by asthma severity with a 4-fold or greater HAI antibody titer increases against the novel influenza H1N1 2009 virus following a single administration of Novartis H1N1 vaccine at each dose, combined across age groups [ Time Frame: Measured on Days 1, 8, 21, and 42 ] [ Designated as safety issue: No ]
Proportion of participants stratified by asthma severity achieving a serum HAI antibody titer of 1:40 or greater against influenza H1N1 2009 virus following a single administration of the H1N1 vaccine at each dose, combined across age groups [ Time Frame: Measured on Days 1, 8, 21, 28, and 42 ] [ Designated as safety issue: No ]
Proportion of participants stratified by asthma severity with 4-fold or greater HAI antibody titer increases against H1N1 2009 virus following one or two administrations of H1N1 vaccine at each dose, by age groups and by use of oral steroids [ Time Frame: Measured on Days 1, 8, 21, 28, and 42 ] [ Designated as safety issue: No ]
Proportion of participants stratified by asthma severity achieving a serum HAI antibody titer of 1:40 or greater against the H1N1 2009 virus following one or two administrations of H1N1 vaccine at each dose, by age groups and by usage of oral steroids [ Time Frame: Measured on Days 1, 8, 21, 28, and 42 ] [ Designated as safety issue: No ]
Changes in the Asthma Control Questionnaire (ACQ) score by dose level, by asthma severity group, by dose group + asthma severity group, and overall [ Time Frame: Measured on Days 1 to 21 and 21 to 42 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	350
Study Start Date:	October 2009
Estimated Study Completion Date:	June 2010

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

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

Ages Eligible for Study:	12 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00978120

Locations

United States, Georgia
Emory University
Atlanta, Georgia, United States
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States
United States, North Carolina
Wake Forest University School of Medicine
Winston-Salem, North Carolina, United States
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States
United States, Pennsylvania
University of Pittsburgh Asthma Institute
Pittsburgh, Pennsylvania, United States
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Principal Investigator:

William Busse, MD

University of Wisconsin Medical School

More Information

Publications:

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. Epub 2009 May 7. Erratum in: N Engl J Med. 2009 Jul 2;361(1):102.

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

Responsible Party:	DAIT/NIAID ( Associate Director, Clinical Research Program )
Study ID Numbers:	DAIT-AAIB-flu-001
Study First Received:	September 15, 2009
Last Updated:	November 19, 2009
ClinicalTrials.gov Identifier:	NCT00978120 History of Changes
Health Authority:	United States: Food and Drug Administration; United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Influenza A Virus, H1N1 Subtype
Vaccine

Additional relevant MeSH terms:

Virus Diseases
RNA Virus Infections
Respiratory Tract Diseases

Respiratory Tract Infections
Influenza, Human
Orthomyxoviridae Infections

ClinicalTrials.gov processed this record on February 08, 2010