A Clinical Research Study to Investigate the Safety of Liposomal Cyclosporine A (L-CsA) in Patients with Bronchiolitis Obliterans Syndrome after Allogeneic Hematopoietic Stem Cell Transplantation.

• Register: EUCTR
• Last refreshed on: 1 February 2020
• Main ID: EUCTR2019-000718-13-ES
• Date of registration: 05/11/2019
• Prospective Registration: Yes
• Primary sponsor: Breath Therapeutics Inc.
• Public title: A Clinical Research Study to Investigate the Safety of Liposomal Cyclosporine A (L-CsA) in Patients with Bronchiolitis Obliterans Syndrome after Allogeneic Hematopoietic Stem Cell Transplantation.
• Scientific title: A Phase IIa Multi-Center, Randomized, Single-Blind Safety Study of Liposomal Cyclosporine A to Treat Bronchiolitis Obliterans Syndrome Following Allogeneic Hematopoietic Stem Cell Transplantation. - BOSTON-4
• Date of first enrolment: 27/11/2019
• Target sample size: 24
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-000718-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: yes; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Spain

Contacts

• Name: Chief Medical Officer
• Affiliation: Breath Therapeutics Inc.

• Name: Chief Medical Officer
• Affiliation: Breath Therapeutics Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1.Age = 18 years.
2. Patient must have a history of allo-HSCT, regardless of source of stem cell or donor or indication for allo-HSCT
3. Documented diagnosis of cGvHD in any organ other than the lung. If BOS is the only manifestation of cGvHD, lung biopsy must have been performed before entering the trial to confirm BOS diagnosis.
4.Confirmed diagnosis of BOS Score 1 within > 6 months and < 3 years after allo-HSCT:
FEV1/FVC < 0.7 at Screening Visit AND
Post-bronchodilator FEV1 = 60 and = 79% predicted at Screening Visit AND
=10% decline of FEV1 % predicted within 24 months prior to Screening Visit AND
Absence of acute infection in the respiratory tract.
5. Patient must be capable of understanding the purposes and risks of the study, has given written informed consent, and agrees to comply with the study requirements.
6. Patient is capable of aerosol inhalation.
7. Women of childbearing potential must have a negative serum or urine pregnancy test at screening and at randomization visit.
Are the trial subjects under 18? no
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 22
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion criteria:
1.Active bacterial, viral (as confirmed by multiplex PCR) or fungal infection not successfully resolved at least 4 weeks prior to the Screening Visit.
2.Chronic renal dysfunction with serum creatinine = 2.5 mg/dL or need for renal dialysis.
3.Chronic hepatic dysfunction with serum total bilirubin > 5x upper limit of normal (ULN), transaminases > 5x ULN, or alkaline phosphatase > 5x ULN.
4. Evidence of relapse of the primary malignancy which warranted allogeneic bone marrow transplant.
5. Use of azithromycin within 4 weeks prior to Randomization (Visit 1).
6. Use of zafirlukast during the study period.
7. Chronic oxygen use or use of non-invasive ventilation.
8. Active smokers (i.e. any kind of inhaled nicotine consumption).
9. Pregnant women or women who are unwilling to use appropriate birth control to avoid pregnancy over the course of the clinical trial (for details see Appendix II).
10. Women who are currently breastfeeding.
11. Known hypersensitivity to L-CsA or to cyclosporine A.
12. Patients who do not tolerate administration of inhaled bronchodilators (e.g., salbutamol).
13. Patients with life-expectancy of less than 6 months.
14. Treatments with other Investigational Medicinal Products (IMPs) or previous therapies within four weeks or five times half-life of
the drug, whichever is longer prior to screening and during the study. Participation in registries, considering the before, is allowed.
15. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion
of the necessary procedures.
16. Any co-existing medical condition that in the Investigator’s judgment will substantially increase the risk associated with the patient’s participation in the clinical trial.
17. Pre-scheduled hospitalizations, surgeries or interventions planned
to be performed after obtaining Informed Consent for this study.


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

Health Condition(s) or Problem(s) studied

Bronchiolitis Obliterans Syndrome in Patients Following Allogeneic Hematopoietic Stem Cell Transplantation

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: Liposomal Cyclosporine A
Product Code: L-CsA
Pharmaceutical Form: Powder and solvent for nebuliser solution
INN or Proposed INN: Ciclosporin (Ciclosporinium)
CAS Number: 59865-13-3
Other descriptive name: CICLOSPORIN A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Powder and solvent for nebuliser solution
Route of administration of the placebo: Inhalation use

Product Name: Liposomal Cyclosporine A
Product Code: L-CsA
Pharmaceutical Form: Powder and solvent for nebuliser solution
INN or Proposed INN: Ciclosporin (Ciclosporinium)
CAS Number: 59865-13-3
Other descriptive name: CICLOSPORIN A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Powder and solvent for nebuliser solution
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Main Objective: The primary objective of this study is to assess the tolerability and safety, of two dose levels of aerosolized L-CsA vs placebo in addition to SoC therapy for the treatment of BOS in adult allo-HSCT recipients.

Timepoint(s) of evaluation of this end point: IMP tolerability and safety during the first 4 weeks of treatment

Please refer to 'Schedule of Activities' in the Protocol

Primary end point(s): IMP tolerability and safety during the first 4 weeks of treatment

IMP Tolerability Parameters:
• Local Tolerability:
o Cough
o Wheezing
o Bronchospasm
o Throat irritation
o Change in FEV1

•Overall Tolerability:
o Clinical Global Impressions (CGI) scale
o Investigator’s tolerability assessment at Visit 3

Safety Parameters:
• Adverse events (AEs)
• Serious adverse events (SAEs)
• Clinical laboratory values
• Vital signs

Secondary Objective: The secondary objectives of this study are to assess PK and exploratory efficacy and quality of life of two dose levels of aerosolized L-CsA vs placebo in addition to SoC therapy for the treatment of BOS in adult allo-HSCT recipients.

Secondary Outcome(s)

Secondary end point(s): IMP tolerability and safety during the first 12 weeks of treatment;

IMP Tolerability Parameters:
• Local Tolerability:
o Cough
o Wheezing
o Bronchospasm
o Throat irritation
o Change in FEV1

•Overall Tolerability:
o Clinical Global Impressions (CGI) scale
o Investigator’s tolerability assessment at Visit 3

Safety Parameters:
• Adverse events (AEs)
• Serious adverse events (SAEs)
• Clinical laboratory values
• Vital signs

CsA Pharmacokinetic Parameters:
o Cmax
o tmax
o AUC0-4h
• Whole blood trough levels

Timepoint(s) of evaluation of this end point: IMP tolerability and safety during the first 12 weeks of treatment;

Pharmacokinetic Parameters:
• PK: (Week 0) at pre-dose; directly after end of inhalation; 15, 30, and 45 minutes, and 1, 1.5, 2, and 4 hours after end of inhalation:
• Whole blood trough levels (at Weeks 2, 4, 8, and 12)

Please refer to 'Schedule of Activities' in the Protocol

Secondary ID(s)

BT–L-CsA–201–SCT

Source(s) of Monetary Support

Breath Therapeutics Inc.

Ethics review

Status: Approved
Approval date: 13/11/2019
Contact: