Phase 2 Study in IPF Patients of Tralokinumab, Anti-IL-13 Antibody, Stopped for Lack of Efficacy
Interim results of a Phase 2 clinical trial found an investigative antibody, tralokinumab, failed to demonstrate potential to improve the respiratory function of patients with idiopathic pulmonary fibrosis (IPF). Based on this final, the study has been closed.
This and additional safety data were reported in the study “A Phase 2 Randomized Controlled Study of Tralokinumab in Subjects with Idiopathic Pulmonary Fibrosis,” published in the American Journal of Respiratory and Critical Care Medicine.
Tralokinumab is an antibody developed by MedImmune to specifically bind to interleukin-13 (IL-13), preventing it from binding to its receptor. A preclinical study demonstrated that the antibody could reduce lung tissue fibrosis in mice.
The Phase 2 trial (NCT01629667) aimed to evaluate the safety, tolerability, and efficacy of tralokinumab compared to placebo in people with mild to moderate IPF. It enrolled 173 patients across 48 sites in Australia, Canada, Israel, Peru, South Korea, and the United States. Patients were randomized to receive intravenously 400 or 800 mg of tralokinumab or placebo every four weeks for up to 68 weeks.
Results from an interim analysis at 52 weeks of treatment revealed that tralokinumab was overall safe and well-tolerated.
But tralokinumab did not show a potential to treat IPF in people. Interim efficacy data found that the anti-IL-13 antibody failed to achieve the trial’s primary endpoint, a significant change in mean percent-predicted force vital capacity (%pFVC; a measure of lung function) compared to placebo, at either dose level. In fact, some treated patients fared worse than those on placebo.
“The percentage of subjects with decline in percent predicted FVC greater than or equal to 10% at Week 52 was numerically greater for tralokinumab-treated subjects compared with placebo,” the study noted.
Patients in tralokinumab-treated groups also showed continuing physical decline, with negative results in the 6-minute walking test (6MWT; a measure of exercise capacity). The treatment’s inability to prevent disease progression, another secondary endpoint, was also seen in the percentage of respiratory-related deaths and those for any reason, which were similar across therapy and placebo groups.
“Due to the lack of efficacy demonstrated by tralokinumab for the primary endpoint at this interim analysis, the independent Data Safety Monitoring Board recommended stopping the study early,” the researchers wrote.
Trial results, they concluded, showed that “blockade of interleukin-13 alone does not result in a significant clinical response across multiple clinical parameters in subjects with mild to moderate idiopathic pulmonary fibrosis (IPF),” and is not a “sufficient” way of halting disease progression.
The most common treatment-related adverse events reported were infusion-related reactions, headache, and diarrhea. Their frequency was similar in treated and placebo groups.