TABLE 2

Study endpoints

Primary endpoints:
 Pharmacokinetics: AUCτ,ss based on sampling at steady state (at week 2 and week 26)
 Number (%) of patients with treatment-emergent adverse events at week 24
Secondary endpoints:
 Number (%) of patients with treatment-emergent pathological findings of epiphyseal growth plate on imaging at week 24 and week 52#
 Number (%) of patients with treatment-emergent pathological findings on dental examination or imaging at week 24 and week 52#
 Number (%) of patients with treatment-emergent adverse events over the whole trial
 Change in height, sitting height, leg length from baseline at week 24, week 52#, week 76# and week 100#
 Change in FVC% predicted from baseline at week 24 and week 52#
 Absolute change from baseline in PedsQL at week 24 and week 52#
 Change in SpO2 on room air at rest from baseline at week 24 and week 52#
 Change in 6-min walk distance from baseline at week 24 and week 52#
 Patient acceptability based on the size of capsules at week 24
 Patient acceptability based on the number of capsules at week 24
 Time to first respiratory-related hospitalisation over the whole trial
 Time to first acute ILD exacerbation or death over the whole trial
 Time to death over the whole trial
Further endpoints
 Number (%) of patients with increase/decrease in FVC% predicted (5–10%; >10%) at week 24 and week 52#
 Number (%) of patients with ≥4.4-point increase in PedsQL from baseline at week 24 and week 52#
 Number (%) of patients with >4% increase in SpO2 on room air from baseline at week 24 and week 52#
 Change in calculated Fan severity score from baseline at week 24 and week 52#
 Change in HAZ score from baseline at week 24 and week 52#
 Change in WAZ score from baseline at week 24 and week 52#
 Slope of HAZ over whole trial
 Slope of WAZ over whole trial
 Number of missed school days due to the disease under study at week 24
 Absolute change from baseline in log-transformed CA-125 at week 24 and week 52
Pharmacokinetic endpoints at Visit 3 (week 2) and Visit 7 (week 26)
Cmax,ss
tmax,ss
t1/2,ss
 CL/Fss
 Vz/Fss
Cpre,ss

Other parameters may be calculated as deemed appropriate. AUCτ,ss: area under the plasma concentration–time curve at steady state; CL/Fss: apparent clearance of the analyte in the plasma at steady state following extravascular multiple dose administration; Cmax,ss: maximum measured concentration of the analyte in plasma at steady state; Cpre,ss: pre-dose concentration of the analyte in plasma at steady state immediately before administration of the next dose; FVC: forced vital capacity; HAZ: height-for-age z-score; ILD: interstitial lung disease; PedsQL: Pediatric Quality of Life Questionnaire; SpO2: oxygen saturation measured by pulse oximetry; t1/2,ss: terminal half-life of the analyte in plasma at steady state; tmax,ss: time from dosing to maximum measured concentration of the analyte in plasma at steady state; Vz/Fss: apparent volume of distribution during the terminal phase λz at steady state following extravascular administration; WAZ: weight-for-age z-score. #: 52 weeks, 76 weeks and 100 weeks time points will not be available for all patients.