The National Institutes of Health is preparing to launch the first government-sponsored clinical trial to determine what dose of the 2009 H1N1 influenza vaccine is needed to induce a protective immune response in people with asthma, especially those with severe disease. The study is cosponsored by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Heart, Lung, and Blood Institute (NHLBI), both part of NIH.

"People with severe asthma often take high doses of glucocorticoids that can suppress their immune system, placing them at greater risk for infection and possibly serious disease caused by 2009 H1N1 influenza virus," says NIAID Director Anthony S. Fauci, M.D. "We need to determine the optimal dose of 2009 H1N1 influenza vaccine that can be safely administered to this at-risk population and whether one or two doses are needed to produce an immune response that is predictive of protection."

The study plan has been submitted to the Food and Drug Administration for review. With FDA allowing it to proceed, the clinical trial will be conducted at seven sites across the United States that participate in NHLBI's Severe Asthma Research Program.

This program already has a well-characterized group of participants with mild, moderate or severe asthma who may be eligible for this new study. These groups are largely distinguished by the amount and frequency of glucocorticoids needed to control asthma symptoms. People with mild disease may not need glucocorticoids, or may require low doses of inhaled glucocorticoids; those with moderate asthma need low to moderate doses of inhaled glucocorticoids; and those with severe asthma need high doses of inhaled glucocorticoids and frequently use oral glucocorticoids as well.

Individuals who already have been infected with 2009 H1N1 influenza or have received a 2009 H1N1 influenza vaccination will not be eligible for the study.

"The results of this study will have immediate implications for individuals with severe asthma as well as those who have milder asthma," says NHLBI Director Elizabeth G. Nabel, M.D.

Early results from other clinical trials of 2009 H1N1 influenza vaccines in healthy adults have shown that a single 15-microgram dose of 2009 H1N1 influenza vaccine without adjuvant is well tolerated and induces a strong immune response in most participants. The same vaccine also generates an immune response that is expected to be protective in healthy children ages 10 to 17 years. Ongoing trials are comparing the immune response to one and two doses of 15- or 30-micrograms of vaccine given three weeks apart in various populations.

The Centers for Disease Control and Prevention has recommended that certain at-risk populations receive the new H1N1 vaccine as a priority before the general population. These target populations include pregnant women, health care providers and individuals with underlying chronic medical conditions, including asthma.

People who have severe asthma may be particularly at risk for infection with the 2009 H1N1 influenza virus. A report published in 2004 suggested that some people who took high doses of glucocorticoids to treat their asthma may receive less protection from influenza vaccines against some strains of influenza. Early in the 2009 H1N1 flu outbreak a CDC review of hospital records found that people with asthma have a four-fold increased risk of being hospitalized with infection compared to the general population.

The study will enroll approximately 350 people with mild, moderate and severe asthma. Participants will be organized into two groups: those with mild or moderate asthma and those with severe asthma. Half of the participants in each group will receive a 15-microgram dose of vaccine, and the other half a 30-microgram dose. Three weeks later, each participant will receive a second dose of the same amount. The strength of the immune response induced by the vaccine will be determined in blood samples by measuring the level of antibodies against 2009 H1N1 flu virus.

Safety data will be collected and examined throughout the course of the study by trial investigators and by an independent safety monitoring committee. Participants will be monitored for any side effects they may experience because of the vaccine, as well as asthma attacks that occur during the study period.