Primary 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 BOS in adult allo-HSCT recipients. Secondary Objectives: 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 BOS in adult allo-HSCT recipients.
This is a Phase II prospective, multi-center, single-blind, randomized clinical trial evaluating safety and tolerability in adult recipients of an allo-HSCT with BOS. Twenty-four patients were planned for enrollment; but, at the time of the premature termination of this study, a total of 11 patients were screened for the study, of whom 5 patients did not fulfill the inclusion criteria and 6 patients were randomly allocated 1:1:1 in 3 treatment groups (L-CsA 10 mg + SoC, L-CsA 5 mg + SoC, or placebo + SoC). A total of 18 centers in 3 countries (France, Germany, and Spain) in Europe were initiated for this multi-center study. IMP was administered for up to 12 weeks treatment period. With low patient recruitment, the BOSTON-4 safety and tolerability study was terminated early by the sponsor on 18 March 2022. This decision was made after a careful and due diligent analysis performed by Zambon of the study status and considering the impact of coronavirus disease 2019 (COVID-19) pandemic on sites activities. From the beginning of the study, in December 2019, only 6 patients were randomized. So it was estimated that continuing the trial with the current protocol and setting would have taken another 9 years for the study to complete.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
6
Liposomal Cyclosporine A is administered at different dosages in the first two arms (10 mg bid and 5 mg bid, respectively) with a new technology of nebulizing liquid drugs, creating an aerosol with a low ballistic momentum and a high percentage of droplets in a respirable size range of 3-5 μm
Liposomal Placebo is administered with the same new technology of nebulizing liquid drugs used for L-CsA, creating an aerosol with a low ballistic momentum and a high percentage of droplets in a respirable size range of 3-5 μm
CHU Hôpital Sud
Amiens, France
Centre Hospitalier Universitaire d'Angers
Angers, France
Centre Hospitalier Universitaire Grenoble Alpes - Hopital Albert Michallon
La Tronche, France
Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez
Lille, France
CHU de Nancy, Hopital Brabois
Nancy, France
CHU de Nantes - Hotel-Dieu
Nantes, France
Hopital Saint Louis
Paris, France
CHU Hopitaux de Bordeaux - Hôpital Haut-Lévêque
Pessac, France
Universitätsklinikum Köln
Cologne, Germany
St.-Johannes-Hospital
Dortmund, Germany
...and 7 more locations
Number of Local Tolerability Events of Interest From Baseline to Visit 3 (Week 4)
The local tolerability events of interest taken into consideration were: Cough, Wheezing, Bronchospasm, Throat irritation and Change from baseline in FEV1 to Visit 3.
Time frame: at Week 4 (visit 3)
Number of Participants With AE and sAE of Different Level of Severity During the First 4 Weeks of Treatment
An adverse event (AE) is any untoward medical occurrence after exposure to a medicine, which is not necessarily caused by that medicine. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A serious adverse event is an adverse event that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a birth defect.
Time frame: During the first 4 weeks of treatment
Number of Local Tolerability Events of Interest From Baseline to Week 12
The local tolerability events of interest taken into consideration were: Cough, Wheezing, Bronchospasm, Throat irritation and Change from baseline in FEV1 to Visit 3.
Time frame: at Week 12
Number of Participants With AE and sAE of Different Level of Severity During the First 12 Weeks of Treatment
An adverse event (AE) is any untoward medical occurrence after exposure to a medicine, which is not necessarily caused by that medicine. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A serious adverse event is an adverse event that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a birth defect.
Time frame: During the first 12 weeks of treatment
CsA Whole Blood Concentrations and CsA Whole Blood Trough Levels
Whole Blood concentrations (Week 0) are 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, and whole blood trough levels (CsA concentration) at Weeks 2, 4, 8, and 12 were calculated.
Time frame: Weeks 0 (pre-dose, directly after end of inhalation, 15, 30, 45, 60 min, 1.5 h, 2h, 4h), 2, 4, 8, and 12
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