Clinical trial
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
Name
BT - L-CsA - 201 - SCT
Description
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.
Trial arms
Trial start
2020-02-11
Estimated PCD
2022-06-16
Trial end
2022-12-15
Status
Terminated
Phase
Early phase I
Treatment
Liposomal Cyclosporine A
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
Arms:
L-CsA 10 mg plus Standard of Care, L-CsA 5 mg plus Standard of Care
Other names:
L-CsA
Liposomal Placebo
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
Arms:
Liposomal Placebo plus Standard of Care
Other names:
Placebo
Size
6
Primary endpoint
Number of Local Tolerability Events of Interest From Baseline to Visit 3 (Week 4)
at Week 4 (visit 3)
Number of Participants With AE and sAE of Different Level of Severity During the First 4 Weeks of Treatment
During the first 4 weeks of treatment
Eligibility criteria
Inclusion Criteria:
1. Age \>/= 18 years
2. Patient must have a history of allogeneic HSCT, regardless of source of stem cell or donor or indication for allogeneic HSCT
3. Documented diagnosis of chronic Graft versus Host Disease (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 \[Jagasia et al. 2015\] 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.
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.
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.
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'SINGLE', 'maskingDescription': 'This was a single-blind trial. Due to the different appearance of the 3 tested strengths of IMP, a full blinding of the study was not possible. Only the randomized study patients were blinded to study treatment assignment.', 'whoMasked': ['PARTICIPANT']}}, 'enrollmentInfo': {'count': 6, 'type': 'ACTUAL'}}
Updated at
2023-10-03
1 organization
2 products
4 indications
Product
Liposomal Cyclosporine AIndication
Bronchiolitis Obliterans SyndromeOrganization
ZambonProduct
Liposomal PlaceboIndication
Graft-versus-host diseaseIndication
ChronicIndication
Stem Cell Transplant Complications