Hydroxychloroquine in pediatric ILD START randomized controlled in parallel-group, then switch placebo to active drug, and STOP randomized controlled in parallel-group

INTERVENTION: Product Name: hydrochloroquine Pharmaceutical Form: Capsule INN or Proposed INN: hydroxychloroquine CAS Number: 118‐42‐3 Concentration unit: mg/kg milligram(s)/kilogram Concentration type: equal Concentration number: 6.5‐ Pharmaceutical form of the placebo: Capsule Route of administration of the placebo: Oral use Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use Product Name: hydrochloroquine Pharmaceutical Form: Capsule INN or Proposed INN: hydroxychloroquine CAS Number: 118‐42‐3 Concentration unit: mg/kg milligram(s)/kilogram Concentration type: equal Concentration number: 10‐ Pharmaceutical form of the placebo: Capsule Route of administration of the placebo: Oral use Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use CONDITION: interstitial lung disease ; MedDRA version: 20.0 Level: PT Classification code 10022611 Term: Interstitial lung disease System Organ Class: 10038738 ‐ Respiratory, thoracic and mediastinal disorders Therapeutic area: Diseases [C] ‐ Respiratory Tract Diseases [C08] PRIMARY OUTCOME: Main Objective: START HCQ block; To evaluate the efficacy of HCQ after 28 days of treatment in chILD compared to placebo.; ; STOP HCQ block; To evaluate the efficacy of HCQ after 84 days of treatment in chILD compared to Placebo; Primary end point(s): START HCQ block; Relative change trial day 1 (i.e. Visit 2) through day 28 (i.e. Visit 3) and relative change day 28 to day 56, (i.e. Visit 4): change active compound compared to change placebo; ; STOP HCQ block; Relative change trial day 1 (i.e. Visit 2) through day 84 (i.e. Visit 5): change active compound compared to change placebo; Secondary Objective: START HCQ block; ‐ To evaluate the efficacy of HCQ after 56 days of treatment in chILD compared to 28 days.; ‐ To evaluate the safety of HCQ after 28 and 56 days of treatment in chILD.; ‐ To evaluate blood levels of HCQ after 28 and 56 days of treatment in chILD.; ; STOP HCQ block; ‐ To evaluate the efficacy of chronic (> 3 months) HCQ treatment in chILD compared to placebo.; ‐ To evaluate the safety of HCQ after > 3 months of treatment in chILD.; ‐ To evaluate blood levels of HCQ before and after treatment in chILD; Timepoint(s) of evaluation of this end point: 28/56 / 84 days SECONDARY OUTCOME: Secondary end point(s): ‐ For both, START and STOP HCQ blocks absolute and relative change under the active compound from trial day 1 (i.e. Visit 2), to START block: day 28 (i.e. Visit 3), STOP block: day 84 (i.e. Visit 5) each, will be compared to change under placebo. The following variables will be investigated: ; ; ‐ Oxygen saturation (O2‐sat, in room air) (only absolute, as relative already primary outcome) ; ‐ Respiratory rate (RR, in room air) (relative and absolute) ; ; ‐ Retractions (yes/no) ; ‐ Coughing (yes/no) ; ‐ Oxygen demand ; ; ‐ pO2, pCO2 (capillary, in room air) ; ‐ Chest x‐ray ; ‐ Quality‐of‐life ; ‐ Health economics ; ‐ Overall survival ; ‐ Weight for height ; ‐ Cumulative amounts of steroid equivalents. Clinical course of lung disease (since last visit): Healthy/ Sick‐better/ Sick‐same/ Sick‐worse/ Patient died ; ‐ Pulmonary exacerbation (since last visit) ; The following lung function parameters will be assessed: ; FEV1 % predicted (recorded in L), FEV 1 (L), FVC % predicted (recorded in L), FVC (L); MEF 75 (L/s); MEF 50 (L/s); MEF 25 (L/s); TLC (L); ITGV (L); RV (L); R eff (kPa*s/L); R eff predicted (%). ; reference values according to the GLI 2012 lung function regression equations ; ; ‐ 6 minute walking distance (meter) ; ‐ O2‐saturation before and after 6MWT ; ‐ Borg scale ; If > 5y old (If a child = 5 years is already able to perform the listed investigations (spirometry or bodyplethysmography), these should also be performed and documented at the discretion of the investigator.) ; ; ‐ If ventilated: ; Duration (h) of mechanical ventilation ; NO (%), ECMO yes/no, if yes VA/VV, double lumen vs. single lumen, Flow‐rate. ; ; ‐ Safety monitoring ; Adverse events, clinical laboratory values (GOT, Creatinine, gGT, blood count, differential, LDH, potassium, steady state drug level), ECG, ophthalmologic review ; Timepoint(s) of evaluation of this end point: 56 / 84 days INCLUSION CRITERIA: 1)Patients should be clinically stable during baseline (between Visit 1 and 2) for inclusion into the study a) To determine this, attending physicians can use SpO2 in room air for patients on room air or on O2‐supplement; the absolute difference on SpO2 is expected not to be = 5% between Visit 1 and 2. For patients on respiratory support, the summary key parameters should not change = 20% between Visit 1 and 2 and b) No major changes in other medications between Visit 1 and 2 2)Mature newborn = 37 weeks of gestation, age = 3 wks and < 2y or Infants and children (= 2 y and < 18 y) or Adults (=18 and =30 y) or Previously preterm (= 37 weeks of gestation) babies or children and adults of all ages if chILD genetically diagnosed (see inclusion criterion 3.) 3) Diagnosis of chronic (= 3 wks of duration) diffuse parenchymal lung disease (DPLD = chILD), defined in at least one of the following ways: a)