E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of bronchiolitis obliterans syndrome in lung transplant |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of bronchiolitis obliterans syndrome in lung transplant |
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E.1.1.2 | Therapeutic area | Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049202 |
E.1.2 | Term | Bronchiolitis obliterans |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to compare cumulative BOS-free survival of patients receiving L-CsA or placebo. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to compare further efficacy and safety data from L-CsA versus placebo and to evaluate IMP pharmacokinetic (PK) data in whole blood samples and bronchoalveolar lavage (BAL). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Patient’s written informed consent obtained prior to any screening procedure
2.Received a single lung, bilateral lung or heart/lung
transplantation between 6 weeks and 26 weeks prior to first IMP
administration
3.Male or female, >/= 18 years of age
4.Capable of self-administration of medications
5.Capable of understanding the purpose and risk of the clinical trial
6.Received within one week prior to first IMP administration the following immunosuppressive agents and dosages for maintenance therapy:
a) Tacrolimus and
b) Mycophenolate mofetil (MMF) 1 to 3 g/day and
c) Prednisone or any other steroid therapy; tapered down within the first 3 months after transplantation
7. Female patients with childbearing potential must have a negative urine pregnancy test prior to first IMP administration.
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
8.Estimated life expectancy > 6 months
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E.4 | Principal exclusion criteria |
1.Any previous episode of bronchiolitis obliterans (BO) or bronchiolitis obliterans syndrome (BOS) of grade 1 or higher
2.Any active invasive bacterial, viral or fungal infection within one week prior to first IMP administration
3.Received systemic maintenance immunosuppressive therapy other than listed in the inclusion criteria within one week prior to first IMP administration
4.Received any systemic or topical ciclosporin A within one week prior to first IMP administration and /or during the clinical trial
5 Received any systemic or topical Rosuvastatin within one week prior to first IMP administration and /or during the clinical trial
6.Current mechanical ventilation
7.Received a lung re-transplantation
8.Pregnant or breast feeding woman
9.Has known hypersensitivity to ciclosporin A
10.Has a serum creatinine value of more than 265 µmol/L (3 mg/dL) or chronic dialysis (haemodialysis)
11.Unlikely to comply with visits, inhalation procedures or spirometric measurements scheduled in the protocol
12.Receipt of an investigational drug as part of a clinical trial within 4 weeks prior to first administration of IMP
13.Any co-existing medical condition that in the investigator’s judgement will substantially increase the risk associated with the patient’s participation in the clinical trial
14.Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures
15.Patient was previously enrolled in the present clinical trial
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E.5 End points |
E.5.1 | Primary end point(s) |
• Cumulative BOS-free survival during the clinical trial period
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Mean forced expiratory volume in one second (FEV1) at baseline,12, 18 and 24
months after first IMP administration
• Mean FEV1 slope from baseline to 12, 18 and 24 months after first IMP administration
• Mean forced midexpiratory flow (FEF25-75), vital capacity (VC) and total lung capacity (TLC) at baseline, 12,
18 and 24 months after first IMP administration
• Mean single breath diffusion capacity (DLCO) and capillary blood gases at 6, 12, 18
and 24 months after first IMP administration
• Cumulative mean incidence of BOS 12, 18 and 24 months after first IMP
administration
• Cumulative mean incidence of invasive bacteria, viral or fungal infection 12, 18 and 24 months after first IMP
administration
• Cumulative mean incidence of lung graft lost 12, 18 and 24 after first IMP
administration
• Mean walking distance from 6 min walk test at 6, 12, 18 and 24 months after first IMP administration
• Mean cumulative dose of maintenance immunosuppressant 12, 18 and 24 months after first IMP administration
• Mean cumulative number of not protocol procedures required overnight hospital stays 12, 18 and 24 months
after first IMP administration
• Mean level of inflammatory markers and L-CsA from bronchoalveolar lavage (BAL)
from at least two visits during the clinical trial period
• Cumulative overall survival during the clinical trial period
Descriptive Endpoints:
1. Cumulative mean incidence of acute rejection grade A2 or higher 12, 18 and 24 months after first IMP
administration
2. Sucrose levels in BAL (s)
Safety Endpoints:
1. Incidence of treatment-emergent AEs including clinically relevant laboratory parameters and vital signs
2. Clinical Laboratory parameters
3. Vital signs
4. Physical Examination
5. L-CsA and tacrolimus PK full & trough levels
Descriptive endpoints:
•Cumulative mean incidence of acute rejection grade A2 or higher 12, 18 and 24 months after first IMP administration
•Sucrose levels in BAL(s)
Safety endpoints:
•Treatment-emergent adverse events (AEs) including clinically relevant laboratory parameters and vital signs
•Clinical laboratory parameters
•Vital signs
•Physical examination
•Full and Trough L-CsA and tacrolimus PK blood levels
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Belgium |
Canada |
Denmark |
Germany |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 42 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 42 |
E.8.9.2 | In all countries concerned by the trial days | 0 |