Application of structured statistical analyses to identify a biomarker predictive of enhanced tralokinumab efficacy in phase III clinical trials for severe, uncontrolled asthma

Table 4 Analysis of key secondary endpoints by baseline FeNO concentration in the STRATOS 1 all-comers population (full analysis set)^a

Change from baseline in	FeNO cut-off, ppb	Tralo Q2W vs. combined placebo^b, n	Treatment effect (95% CI)	p-value
FEV₁, %	≥37	87 vs. 92	12.80 (5.34, 20.26)	< 0.001
FEV₁, %	< 37	268 vs. 269	3.83 (− 0.46, 8.12)	0.080
ACQ-6 score	≥37	75 vs. 83	−0.43 (− 0.71, − 0.16)	0.002
ACQ-6 score	< 37	242 vs. 231	− 0.07 (− 0.23, 0.09)	0.372
AQLQ score	≥37	74 vs. 83	0.53 (0.22, 0.84)	< 0.001
AQLQ score	< 37	241 vs. 230	0.02 (−0.16, 0.20)	0.860
Total Asthma Symptom Score	≥37	71 vs. 68	−0.05 (− 0.34, 0.24)	0.720
Total Asthma Symptom Score	< 37	242 vs. 243	−0.10 (− 0.26, 0.06)	0.222

ACQ-6 Asthma Control Questionnaire (6-item), AQLQ Standardised Asthma Quality of Life Questionnaire for 12 Years and Older, CI Confidence interval, FeNO Fractional exhaled nitric oxide, FEV₁ Forced expiratory volume in 1 s, Q2W Every 2 weeks, Q4W Every 4 weeks, Tralo Tralokinumab
^aThe two treatment arms were compared with the pooled placebo group using a repeated measures analysis. For percentage change in FEV₁ the model was treatment group + geographical region + age group + periostin group at baseline + number of exacerbations in the previous year + visit + treatment*visit + treatment*biomarker group using an unstructured variance-covariance matrix. For change in score the model was baseline score + treatment group + geographical region + age group + periostin group at baseline + number of exacerbations in the previous year + visit + treatment*visit + treatment*biomarker group using a compound symmetric variance-covariance matrix. Baseline was the last non-missing measurement recorded prior to randomisation (typically randomisation). No multiplicity adjustments were made and all p-values stated are nominal; values <0.05 are bolded
^bThe placebo treatment group is a combined treatment group (placebo Q2W + placebo Q4W)

ISSN: 1471-2466