NIH Launches Phase 2 Trial of Biologic in Urban Youth With Type 2 Allergic Asthma

Little data exist on the effectiveness of dupilumab in Black and Hispanic children, even though severe asthma disproportionately affects these populations.

The National Institutes of Health (NIH) said this week it is conducting a double-blind, placebo-controlled, randomized, phase 2 multicenter clinical trial testing whether the biologic dupilumab can reduce asthma attacks and improve lung function and asthma symptoms in children with poorly controlled allergic asthma who live in low-income urban neighborhoods.

The investigators also aim to define the activity levels of asthma-associated gene networks that correspond to specific health outcomes while these patients are on dupilumab. Most of the participants are expected to be Black or Hispanic; despite the fact that severe asthma disproportionately affects these populations, there is little data exist regarding the effectiveness of dupilumab in these children.

It is hoped that the genetic information will help clarify how dupilumab works at the molecular level and shed light as to why some children who receive the drug nevertheless have asthma attacks.

The National Institute of Allergy and Infectious Diseases (NIAID), part of NIH, is sponsoring and cofunding the trial, called Prevention of Asthma Exacerbations Using Dupilumab in Urban Children and Adolescents, or PANDA (NCT05347771).

Dupilumab is approved by the FDA as an add-on maintenance treatment for certain types of moderate-to-severe asthma in patients ages 6 years and older. It is also approved for use in certain patients with atopic dermatitis and chronic rhinosinusitis with nasal polyposis. Last month, it became the first approved treatment for eosinophilic esophagitis, and earlier this week, the FDA accepted dupilumab, marketed as Dupixent, for priority review for the treatment of prurigo nodularis.

“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, MD, in a statement. “The PANDA trial is an important step toward these goals.”

NIAID, Regeneron Pharmaceuticals, and Sanofi are cofunding the trial. The NIAID-funded Childhood Asthma in Urban Settings (CAUSE) Network is conducting the study at 7 medical centers located in Aurora, Colorado; Boston; Chicago; Cincinnati; New York and Washington, DC.

An estimated 2.26 million U.S. children and adolescents experienced an asthma attack in 2019, according to the CDC.

Black and Hispanic children who live in low-income urban environments who are exposed to both high levels of indoor allergens and traffic-related pollution are at a particularly high risk for asthma that is prone to attacks.

In an earlier study, NIAID-supported investigators identified numerous networks of genes that are activated together and are associated with asthma attacks in these populations.

Some of these gene networks are specifically associated with a systemic allergic response called type 2 inflammation, shown to play a major role in asthma in this population. Because dupilumab works by blocking interleukin 4 and interleukin 13, 2 small proteins involved in type 2 inflammation, the PANDA investigators hypothesize that the drug will reduce asthma attacks and improve lung function and asthma symptoms in study participants.

The PANDA study team will enroll approximately 240 participants ages 6 to 17 years who have poorly controlled allergic asthma that is prone to attacks and who have biological markers of type 2 inflammation. The children will be assigned at random in a 2:1 ratio to receive injections of either dupilumab or a placebo every 2 weeks for a year.

The PANDA study team will measure participants’ lung function and markers of airway inflammation numerous times during the trial. The study team also will collect nasal secretions several times after the first injection―mainly within the first 2 weeks―and twice after the last injection. In addition, when a participant has a cold, which can trigger asthma flares, the study team will collect blood samples and nasal secretions.

RNA will be extracted from cells in the nasal secretions and will be sequenced and analyzed to determine the activity of the gene networks identified in the earlier study. The PANDA investigators will examine relationships between the activity levels of these networks and the children’s clinical responses to dupilumab. In particular, the researchers will look for changes in gene network activity over time and will explore whether activity levels at one point can forecast a later clinical response.

All participants also will receive asthma care based on clinical guidelines.