A phase II, randomised, double-blind, placebo controlled, parallel group,

INTERVENTION: Product Name: Aerolised Liposomal Ciclosporin A Product Code: L‐CsA Pharmaceutical Form: Powder for nebuliser solution INN or Proposed INN: Ciclosporin CAS Number: 59865‐13‐3 Current Sponsor code: 081400 Other descriptive name: Ciclosporine, ciclosporina Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 4‐ Pharmaceutical form of the placebo: Powder for nebuliser solution Route of administration of the placebo: Inhalation use Product Name: Sodium Chloride Solution Product Code: Sodium Chloride solvent Pharmaceutical Form: Nebuliser solution Current Sponsor code: Sodium Chloride Other descriptive name: Sodium Chloride Concentration unit: % (W/W) percent weight/weight Concentration type: equal Concentration number: 0.25‐ CONDITION: Bronchiolitis Obliterans Syndrome ; MedDRA version: 9.1 Level: LLT Classification code 10049202 Term: Bronchiolitis obliterans INCLUSION CRITERIA: 1. Subject’s written informed consent obtained prior to any screening procedure. For subjects below 18 years of age, the written informed consent is obtained from the subject’s legal representative 2.Received an allogeneic haematopoietic stem cell transplantation (HSCT) 3.Has a baseline FEV1 value available prior to HSCT according to Appendix III 4.Has a diagnosis of bronchiolitis obliterans (BOS) of grade 1, 2 or 3 and confirmation to initiate BOS‐specific treatment based on declining FEV1 values according to Appendix III within 1 week prior to first IMP administration 5.Male or female, >/= 12 years of age 6.Capable of self‐administration medications 7.Capable of understanding the purpose and risk of the clinical trial 8.Received at least 1 week prior to first IMP administration the following immunosuppressive agents and dosages for the treatment of chronic graft‐versus‐hostdisease (GVHD) including BOS: a)Tacrolimus approximately 0.1 to PRIMARY OUTCOME: Main Objective: The primary objective is to establish an IMP dosage with the most favourable risk‐benefit ratio for the treatment of BOS in allogeneic HSCT patients. Primary end point(s): Efficacy Endpoint; • Mean forced expiratory volume in one second (FEV1) at baseline, 3, 6, 9 and 12 month after first IMP administration; • Mean FEV1 slope from baseline to 3, 6, 9 and 12 months after first IMP administration; • Mean forced midexpiratory flow (FEF25‐75), vital capacity (VC) and total lung capacity (TLC) at baseline, 3, 6, 9 and 12 months after first IMP administration; • Mean single breath diffusing capacity (DLCO) and capillary blood gases at baseline, 3, 6, 9 and 12 months after first IMP administration; • Cumulative mean incidence of invasive bacterial, viral or fungal infections 3, 6, 9 and 12 months after first IMP administration; • Cumulative mean incidence of acute GVHD at baseline, 3, 6, 9 and 12 months after first IMP administration; • Cumulative mean incidence of chronic GVHD other than BO at baseline, 3, 6, 9 and 12 months after first IMP administration; • Mean walking distance from 6 min walk test at baseline, 3, 6, 9 and 12 months after first IMP administration; • Mean cumulative dose of systemic immunosuppressants 3, 6, 9 and 12 months after first IMP administration; • Mean cumulative number of days without systemic immunosuppressants 3, 6, 9 and 12 months after first IMP administration; • Mean cumulative number of overnight hospital stays 3, 6, 9 and 12 months after first IMP administration; • Mean levels of inflammatory markers and L‐CsA from sputum from at least two visits; during the clinical trial period; • Cumulative overall survival during the clinical trial period; ; Safety; • Incidence of AEs including clinically relevant laboratory findings until EoS; • Mean L‐CsA blood levels at baseline and 3 months after first IMP administration; Secondary Objective: The secondary objectives are to compare efficacy and safety data from IMP versus placebo and to evaluate IMP PK data in whole blood and sputum samples.