A phase II, randomised, double-blind, placebo controlled, parallel group, dose-finding clinical trial to investigate the efficacy and safety of 10 and 20 mg/day aerosolised liposomal ciclosporin A (L-CsA) versus placebo in the treatment of bronchiolitis obliterans syndrome (BOS) in allogeneic haematopoietic stem cell transplant (HSCT) patients

• Register: EUCTR
• Last refreshed on: 14 August 2012
• Main ID: EUCTR2008-003801-15-GB
• Date of registration: 24/11/2010
• Prospective Registration: No
• Primary sponsor: PARIPharma GmbH
• Public title: A phase II, randomised, double-blind, placebo controlled, parallel group, dose-finding clinical trial to investigate the efficacy and safety of 10 and 20 mg/day aerosolised liposomal ciclosporin A (L-CsA) versus placebo in the treatment of bronchiolitis obliterans syndrome (BOS) in allogeneic haematopoietic stem cell transplant (HSCT) patients
• Scientific title: A phase II, randomised, double-blind, placebo controlled, parallel group, dose-finding clinical trial to investigate the efficacy and safety of 10 and 20 mg/day aerosolised liposomal ciclosporin A (L-CsA) versus placebo in the treatment of bronchiolitis obliterans syndrome (BOS) in allogeneic haematopoietic stem cell transplant (HSCT) patients
• Date of first enrolment: 26/02/2009
• Target sample size: 70
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-003801-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

United Kingdom

Key inclusion & exclusion criteria

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 0.2 mg/kg/day adjusted to a target trough serum level (C0) of 5 to 15 µg/L
b)Prednisone 1 to 3 mg/kg/day for 2 to 6 weeks, tapered down subsequently
9.Female patients with reproductive potential must have a negative serum pregnancy test within 3 days prior to screening. Both women and men must agree to use a medically acceptable method of contraception throughout the IMP treatment period and for 3 months after IMP discontinuation. Acceptable methods of contraception are disclosed in Appendix II of the protocol
10.Estimated life expectancy > 6 months

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Received systemic or topical ciclosporin A within one week prior to IMP administration and during the clinical trial
2.Any active invasive bacterial, viral or fungal infection within one week prior to first IMP admiistration
3.Received systemic immunosuppressive therapy for chronic GVHD other than listed in the inclusion criteria within one week prior to first IMP administration
4.Has steroid-refractory or steroid-intolerant chronic GVHD due to insulin-dependent diabetes or symptomatic avascular necrosis
5.Current mechanical ventilation
6.Pregnant or breast-feeding woman
7.Has a known hypersensitivity to ciclosporin A
8.Has a serum creatinine value of more than 265 µmol/L (3 mg/dL) or chronic dialysis (haemodialysis)
9.Unlikely to comply with the visits, inhalation procedures or spirometric measurements scheduled in the protocol
10.Receipt of an investigational drug as part of a clinical trial within 4 weeks prior to first administration of IMP
11.Any co-existing medical condition that in the investigator’s judgement will substantially increase the risk associated with the subject’s participation in the clinical trial
12.Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures
13.Subject was previously included in the present clinical trial



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Bronchiolitis Obliterans Syndrome
MedDRA version: 9.1 Level: LLT Classification code 10049202 Term: Bronchiolitis obliterans

Intervention(s)

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-

Primary Outcome(s)

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.

Secondary ID(s)

12011.202