A phase II placebo-controlled study of tralokinumab in moderate-to-severe asthma

Abstract

Pre-clinical data demonstrate a pivotal role for interleukin (IL)-13 in the development and maintenance of asthma. This study assessed the effects of tralokinumab, an investigational human IL-13-neutralising immunoglobulin G4 monoclonal antibody, in adults with moderate-to-severe uncontrolled asthma despite controller therapies. 194 subjects were randomised to receive tralokinumab (150, 300 or 600 mg) or placebo subcutaneously every 2 weeks. Primary end-point was change from baseline in mean Asthma Control Questionnaire score (ACQ-6; ACQ mean of six individual item scores) at week 13 comparing placebo and combined tralokinumab dose groups. Secondary end-points included pre-bronchodilator lung function, rescue β(2)-agonist use and safety. Numerical end-points are reported as mean±sd. At week 13, change from baseline in ACQ-6 was -0.76±1.04 for tralokinumab versus -0.61±0.90 for placebo (p=0.375). Increases from baseline in forced expiratory volume in 1 s (FEV(1)) were 0.21±0.38 L versus 0.06±0.48 L (p=0.072), with a dose-response observed across the tralokinumab doses tested. β(2)-agonist use (puffs per day) was decreased for tralokinumab -0.68±1.45 versus placebo -0.10±1.49 (p=0.020). The increase in FEV(1) following tralokinumab treatment remained evident 12 weeks after the final dose. Safety profile was acceptable with no serious adverse events related to tralokinumab. No improvement in ACQ-6 was observed, although tralokinumab treatment was associated with improved lung function.

Trial registration: ClinicalTrials.gov NCT00873860.

Figure 1–

Subject disposition. Evaluable population comprised subjects who received at least four doses of study medication. Subjects who received at least one dose but discontinued prior to receiving four doses due to safety reasons were also included in the evaluable population. ACQ-6: Asthma Control Questionnaire, mean of six individual item scores.

Figure 2–

Mean (se) change from baseline in a) Asthma Control Questionnaire, mean of six individual item scores (ACQ-6) score, and b) pre-bronchodilator forced expiratory volume in 1 s (FEV₁) over time (evaluable population). ----: week 13, primary end-point.

Figure 3–

Mean (se) change from baseline in a) Asthma Control Questionnaire, mean of six individual item scores (ACQ-6) score, and b) pre-bronchodilator forced expiratory volume in 1 s (FEV₁) over time (evaluable population) in the subpopulation (n=56) who supplied a sputum sample at baseline. Placebo (sputum: all) placebo: n=17; tralokinumab (sputum: all): n=39; tralokinumab-treated group without measurable IL-13 (sputum IL-13 <10 pg·mL⁻¹; n=28) and those with measurable IL-13 (sputum IL-13 ≥10 pg·mL⁻¹; n=11).