The National Institutes of Health initiated a clinical trial to see if dupilumab, a monoclonal antibody, will help children with poorly controlled allergic asthma who live in low-income urban areas minimize asthma attacks and improve lung function and asthma symptoms.
The researchers also want to figure out how the activity levels of asthma-related gene networks correlate with specific health outcomes following antibody treatment in these kids, who are mostly Black or Hispanic.
The Prevention of Asthma Exacerbations Using Dupilumab in Urban Children and Adolescents, or PANDA, trial is sponsored and co-funded by the National Institute of Allergy and Infectious Diseases (NIAID), which is part of the National Institutes of Health.
The US Food and Drug Administration has approved dupilumab as an add-on maintenance treatment for certain forms of moderate-to-severe asthma in people aged 6 and up.
However, there is no information on the drug’s effectiveness in Black and Hispanic children, despite the fact that severe asthma affects these racial and ethnic groups disproportionately. This knowledge vacuum will be filled by the new NIAID project.
“We need to find out how well approved asthma drugs work for disadvantaged children of color living in urban areas, and whether biological markers can help predict how the drugs affect their asthma,” said NIAID Director Anthony S. Fauci, M.D. “The PANDA trial is an important step toward these goals.”
The Phase 2 trial is being co-funded by NIAID, Regeneron Pharmaceuticals, Inc., and Sanofi. The study is being carried out by the NIAID-funded Childhood Asthma in Urban Settings (CAUSE) Network at seven medical sites in Aurora, Colorado, Boston, Chicago, Cincinnati, New York, and Washington, D.C. Daniel J. Jackson, M.D., a professor of pediatrics and medicine at the University of Wisconsin-School Madison’s of Medicine and Public Health, is leading the trial. The trial will use dupilumab and a matching placebo donated by Regeneron and Sanofi.
Asthma is characterized by chronic inflammation of the airways. The airway lining expands, the muscles surrounding the airways tighten, and the airways generate additional mucus during an asthma episode, significantly limiting the area for air to pass in and out of the lungs.
According to the Centers for Disease Control and Prevention, 2.26 million children and adolescents in the United States had an asthma episode in 2019.
Children of color, particularly black and Hispanic children, who live in low-income metropolitan areas in the United States, are at a higher risk of developing asthma that is prone to attacks.
These youngsters are frequently allergic to a variety of things and are exposed to high amounts of indoor allergens as well as pollution from traffic, which can make asthma even more difficult to manage.
NIAID-funded researchers identified multiple networks of genes that are active simultaneously and are linked to asthma attacks in minority children and adolescents living in low-income urban settings in a previous study(link is external).
Some of these gene networks have been linked to a systemic allergic response known as Type 2 inflammation, which has been linked to asthma in this population.
The PANDA investigators believe that dupilumab will reduce asthma attacks and enhance lung function and asthma symptoms in study participants because it acts by suppressing interleukin 4 and interleukin 13, two tiny proteins implicated in Type 2 inflammation.
The PANDA research will enroll about 240 children and teenagers aged 6 to 17 who have poorly managed allergic asthma that is prone to attacks and have biochemical signs of Type 2 inflammation.
The youngsters will be randomly assigned to receive injections of dupilumab or a placebo every two weeks for a year in a 2:1 ratio. Until the trial is completed, no one will know who will receive which type of injection.
All patients will also receive asthma treatment based on guidelines developed by the National Heart, Lung, and Blood Institute, which is part of the National Institutes of Health.
Throughout the trial, the PANDA study team will take many measurements of patients’ lung function and signs of airway inflammation.
Nasal secretions will be collected multiple times after the initial injection, primarily within the first two weeks, and twice following the final injection.
The study team will also collect blood samples and nasal secretions when a subject gets a cold, which can aggravate asthma symptoms.
RNA, a type of genetic material, will be collected from cells in nasal secretions and sequenced and studied to see if the gene networks revealed in the previous study are still active.
The PANDA researchers will look into the relationship between these networks’ activity levels and the children’s clinical responses to dupilumab.
The researchers will check for changes in gene network activity over time, as well as see if activity levels at one moment can predict clinical response later on.
The researchers expect that this knowledge will help them understand how dupilumab works at the molecular level and why some children who take it still suffer asthma attacks.