Trial Outcomes & Findings for A Safety Study of Liposomal Cyclosporine A to Treat Bronchiolitis After Hematopoietic Transplant (BOSTON-4) (NCT NCT04107675)
NCT ID: NCT04107675
Last Updated: 2023-10-03
Results Overview
The local tolerability events of interest taken into consideration were: Cough, Wheezing, Bronchospasm, Throat irritation and Change from baseline in FEV1 to Visit 3.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
6 participants
Primary outcome timeframe
at Week 4 (visit 3)
Results posted on
2023-10-03
Participant Flow
From the start of the trial, only 6 patients were randomized. With low patient recruitment, the BOSTON-4 safety and tolerability study was terminated early 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. So, due to this low recruitment, the Sponsor decided to early terminate the trial, on 18 March 2022.
Participant milestones
| Measure |
L-CsA 10 mg Plus Standard of Care
Liposomal Cyclosporine A 10 mg (10 mg/2.5 mL) bid, once in the morning and once in the evening, for up to 12 weeks.
The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 8 to 13 minutes for the 0- and 10-mg doses.
Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
L-CsA 5 mg Plus Standard of Care
Liposomal Cyclosporine A 5 mg (5 mg/1.25 mL) bid, once in the morning and once in the evening, for up to 12 weeks. The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 5 to 10 minutes for the 5-mg dose.
Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
Liposomal Placebo Plus Standard of Care
Liposomal Placebo 2.5 mL (0 mg L-CsA/2.5 mL) bid, once in the morning and once in the evening, for up to 12 weeks.
The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 8 to 13 minutes for the 0- and 10-mg doses. Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
|---|---|---|---|
|
Overall Study
STARTED
|
2
|
2
|
2
|
|
Overall Study
COMPLETED
|
2
|
2
|
2
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Safety Study of Liposomal Cyclosporine A to Treat Bronchiolitis After Hematopoietic Transplant (BOSTON-4)
Baseline characteristics by cohort
| Measure |
L-CsA 10 mg Plus Standard of Care
n=2 Participants
Liposomal Cyclosporine A 10 mg (10 mg/2.5 mL) bid, once in the morning and once in the evening, for up to 12 weeks.
The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 8 to 13 minutes for the 0- and 10-mg doses.
Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
L-CsA 5 mg Plus Standard of Care
n=2 Participants
Liposomal Cyclosporine A 5 mg (5 mg/1.25 mL) bid, once in the morning and once in the evening, for up to 12 weeks. The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 5 to 10 minutes for the 5-mg dose.
Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
Liposomal Placebo Plus Standard of Care
n=2 Participants
Liposomal Placebo 2.5 mL (0 mg L-CsA/2.5 mL) bid, once in the morning and once in the evening, for up to 12 weeks.
The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 8 to 13 minutes for the 0- and 10-mg doses. Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
Total
n=6 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Continuous
|
55.5 years
STANDARD_DEVIATION 0.71 • n=5 Participants
|
63.0 years
STANDARD_DEVIATION 0.00 • n=7 Participants
|
46.0 years
STANDARD_DEVIATION 12.73 • n=5 Participants
|
54.8 years
STANDARD_DEVIATION 9.52 • n=4 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Region of Enrollment
France
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
2 participants
n=4 Participants
|
|
Region of Enrollment
Germany
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
2 participants
n=4 Participants
|
|
Region of Enrollment
Spain
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
2 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: at Week 4 (visit 3)Population: The Safety Analysis Set (SAF) was defined as all randomized patients who had received a partial dose of IMP at least once.
The local tolerability events of interest taken into consideration were: Cough, Wheezing, Bronchospasm, Throat irritation and Change from baseline in FEV1 to Visit 3.
Outcome measures
| Measure |
L-CsA 10 mg Plus Standard of Care
n=2 Participants
Liposomal Cyclosporine A 10 mg (10 mg/2.5 mL) bid, once in the morning and once in the evening, for up to 12 weeks.
The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 8 to 13 minutes for the 0- and 10-mg doses.
Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
L-CsA 5 mg Plus Standard of Care
n=2 Participants
Liposomal Cyclosporine A 5 mg (5 mg/1.25 mL) bid, once in the morning and once in the evening, for up to 12 weeks. The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 5 to 10 minutes for the 5-mg dose.
Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
Liposomal Placebo Plus Standard of Care
n=2 Participants
Liposomal Placebo 2.5 mL (0 mg L-CsA/2.5 mL) bid, once in the morning and once in the evening, for up to 12 weeks.
The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 8 to 13 minutes for the 0- and 10-mg doses. Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
|---|---|---|---|
|
Number of Local Tolerability Events of Interest From Baseline to Visit 3 (Week 4)
Change in FEV1
|
0 number of local events
|
1 number of local events
|
1 number of local events
|
|
Number of Local Tolerability Events of Interest From Baseline to Visit 3 (Week 4)
Any Local Tolerability Event
|
1 number of local events
|
5 number of local events
|
4 number of local events
|
|
Number of Local Tolerability Events of Interest From Baseline to Visit 3 (Week 4)
Cough
|
0 number of local events
|
1 number of local events
|
1 number of local events
|
|
Number of Local Tolerability Events of Interest From Baseline to Visit 3 (Week 4)
Wheezing
|
0 number of local events
|
0 number of local events
|
0 number of local events
|
|
Number of Local Tolerability Events of Interest From Baseline to Visit 3 (Week 4)
Bronchospasm
|
0 number of local events
|
0 number of local events
|
0 number of local events
|
|
Number of Local Tolerability Events of Interest From Baseline to Visit 3 (Week 4)
Throat irritation
|
1 number of local events
|
3 number of local events
|
2 number of local events
|
PRIMARY outcome
Timeframe: During the first 4 weeks of treatmentPopulation: The Safety Analysis Set (SAF) was defined as all randomized patients who had received a partial dose of IMP at least once.
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.
Outcome measures
| Measure |
L-CsA 10 mg Plus Standard of Care
n=2 Participants
Liposomal Cyclosporine A 10 mg (10 mg/2.5 mL) bid, once in the morning and once in the evening, for up to 12 weeks.
The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 8 to 13 minutes for the 0- and 10-mg doses.
Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
L-CsA 5 mg Plus Standard of Care
n=2 Participants
Liposomal Cyclosporine A 5 mg (5 mg/1.25 mL) bid, once in the morning and once in the evening, for up to 12 weeks. The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 5 to 10 minutes for the 5-mg dose.
Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
Liposomal Placebo Plus Standard of Care
n=2 Participants
Liposomal Placebo 2.5 mL (0 mg L-CsA/2.5 mL) bid, once in the morning and once in the evening, for up to 12 weeks.
The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 8 to 13 minutes for the 0- and 10-mg doses. Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
|---|---|---|---|
|
Number of Participants With AE and sAE of Different Level of Severity During the First 4 Weeks of Treatment
Any TEAEs
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With AE and sAE of Different Level of Severity During the First 4 Weeks of Treatment
Mild TEAEs
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With AE and sAE of Different Level of Severity During the First 4 Weeks of Treatment
Moderate TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With AE and sAE of Different Level of Severity During the First 4 Weeks of Treatment
Severe TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With AE and sAE of Different Level of Severity During the First 4 Weeks of Treatment
Serious TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With AE and sAE of Different Level of Severity During the First 4 Weeks of Treatment
Related TEAEs
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With AE and sAE of Different Level of Severity During the First 4 Weeks of Treatment
COVID-19 related TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With AE and sAE of Different Level of Severity During the First 4 Weeks of Treatment
Patients discontinued study due to TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With AE and sAE of Different Level of Severity During the First 4 Weeks of Treatment
Patients discontinued treatment due to TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With AE and sAE of Different Level of Severity During the First 4 Weeks of Treatment
TEAEs Leading to Death
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: at Week 12Population: The Safety Analysis Set (SAF) was defined as all randomized patients who had received a partial dose of IMP at least once.
The local tolerability events of interest taken into consideration were: Cough, Wheezing, Bronchospasm, Throat irritation and Change from baseline in FEV1 to Visit 3.
Outcome measures
| Measure |
L-CsA 10 mg Plus Standard of Care
n=2 Participants
Liposomal Cyclosporine A 10 mg (10 mg/2.5 mL) bid, once in the morning and once in the evening, for up to 12 weeks.
The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 8 to 13 minutes for the 0- and 10-mg doses.
Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
L-CsA 5 mg Plus Standard of Care
n=2 Participants
Liposomal Cyclosporine A 5 mg (5 mg/1.25 mL) bid, once in the morning and once in the evening, for up to 12 weeks. The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 5 to 10 minutes for the 5-mg dose.
Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
Liposomal Placebo Plus Standard of Care
n=2 Participants
Liposomal Placebo 2.5 mL (0 mg L-CsA/2.5 mL) bid, once in the morning and once in the evening, for up to 12 weeks.
The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 8 to 13 minutes for the 0- and 10-mg doses. Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
|---|---|---|---|
|
Number of Local Tolerability Events of Interest From Baseline to Week 12
Any Local Tolerability Event
|
1 number of events
|
7 number of events
|
6 number of events
|
|
Number of Local Tolerability Events of Interest From Baseline to Week 12
Cough
|
0 number of events
|
2 number of events
|
2 number of events
|
|
Number of Local Tolerability Events of Interest From Baseline to Week 12
Wheezing
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Number of Local Tolerability Events of Interest From Baseline to Week 12
Bronchospasm
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Number of Local Tolerability Events of Interest From Baseline to Week 12
Throat irritation
|
1 number of events
|
4 number of events
|
3 number of events
|
|
Number of Local Tolerability Events of Interest From Baseline to Week 12
Change in FEV1
|
0 number of events
|
1 number of events
|
1 number of events
|
SECONDARY outcome
Timeframe: During the first 12 weeks of treatmentPopulation: The Safety Analysis Set (SAF) was defined as all randomized patients who had received a partial dose of IMP at least once.
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.
Outcome measures
| Measure |
L-CsA 10 mg Plus Standard of Care
n=2 Participants
Liposomal Cyclosporine A 10 mg (10 mg/2.5 mL) bid, once in the morning and once in the evening, for up to 12 weeks.
The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 8 to 13 minutes for the 0- and 10-mg doses.
Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
L-CsA 5 mg Plus Standard of Care
n=2 Participants
Liposomal Cyclosporine A 5 mg (5 mg/1.25 mL) bid, once in the morning and once in the evening, for up to 12 weeks. The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 5 to 10 minutes for the 5-mg dose.
Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
Liposomal Placebo Plus Standard of Care
n=2 Participants
Liposomal Placebo 2.5 mL (0 mg L-CsA/2.5 mL) bid, once in the morning and once in the evening, for up to 12 weeks.
The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 8 to 13 minutes for the 0- and 10-mg doses. Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
|---|---|---|---|
|
Number of Participants With AE and sAE of Different Level of Severity During the First 12 Weeks of Treatment
Any TEAEs
|
2 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With AE and sAE of Different Level of Severity During the First 12 Weeks of Treatment
Mild TEAEs
|
2 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With AE and sAE of Different Level of Severity During the First 12 Weeks of Treatment
Moderate TEAEs
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With AE and sAE of Different Level of Severity During the First 12 Weeks of Treatment
Severe TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With AE and sAE of Different Level of Severity During the First 12 Weeks of Treatment
Serious TEAEs
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With AE and sAE of Different Level of Severity During the First 12 Weeks of Treatment
Related TEAEs
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With AE and sAE of Different Level of Severity During the First 12 Weeks of Treatment
COVID-19 related TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With AE and sAE of Different Level of Severity During the First 12 Weeks of Treatment
Patients discontinued study due to TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With AE and sAE of Different Level of Severity During the First 12 Weeks of Treatment
Patients discontinued treatment due to TEAEs
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With AE and sAE of Different Level of Severity During the First 12 Weeks of Treatment
TEAEs Leading to Death
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Weeks 0 (pre-dose, directly after end of inhalation, 15, 30, 45, 60 min, 1.5 h, 2h, 4h), 2, 4, 8, and 12Population: The Full Analysis Set (FAS) was defined as all randomized patients for whom at least 1 post-baseline measurement of an efficacy outcome measure (ie, spirometry or quality of life measures) was available. For spirometry measures, baseline corresponded to the assessment at randomization visit (Visit 1) prior to inhalation of IMP.
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.
Outcome measures
| Measure |
L-CsA 10 mg Plus Standard of Care
n=2 Participants
Liposomal Cyclosporine A 10 mg (10 mg/2.5 mL) bid, once in the morning and once in the evening, for up to 12 weeks.
The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 8 to 13 minutes for the 0- and 10-mg doses.
Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
L-CsA 5 mg Plus Standard of Care
n=2 Participants
Liposomal Cyclosporine A 5 mg (5 mg/1.25 mL) bid, once in the morning and once in the evening, for up to 12 weeks. The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 5 to 10 minutes for the 5-mg dose.
Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
Liposomal Placebo Plus Standard of Care
n=2 Participants
Liposomal Placebo 2.5 mL (0 mg L-CsA/2.5 mL) bid, once in the morning and once in the evening, for up to 12 weeks.
The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 8 to 13 minutes for the 0- and 10-mg doses. Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
|---|---|---|---|
|
CsA Whole Blood Concentrations and CsA Whole Blood Trough Levels
Week 0 - predose
|
12.2115 ng/ml
Standard Deviation 17.26967
|
0.0000 ng/ml
Standard Deviation 0.0000
|
11.7750 ng/ml
Standard Deviation 16.65236
|
|
CsA Whole Blood Concentrations and CsA Whole Blood Trough Levels
Directly after end of inhalation
|
84.6510 ng/ml
Standard Deviation 69.82821
|
19.3420 ng/ml
Standard Deviation 15.91980
|
12.1760 ng/ml
Standard Deviation 17.21946
|
|
CsA Whole Blood Concentrations and CsA Whole Blood Trough Levels
15 min
|
73.5110 ng/ml
Standard Deviation 59.82123
|
30.0500 ng/ml
Standard Deviation 24.34003
|
11.2440 ng/ml
Standard Deviation 15.90142
|
|
CsA Whole Blood Concentrations and CsA Whole Blood Trough Levels
30 min
|
68.3640 ng/ml
Standard Deviation 60.56228
|
26.9400 ng/ml
Standard Deviation 22.19184
|
13.1780 ng/ml
Standard Deviation 18.63651
|
|
CsA Whole Blood Concentrations and CsA Whole Blood Trough Levels
45 min
|
70.1555 ng/ml
Standard Deviation 64.88483
|
23.2780 ng/ml
Standard Deviation 18.52761
|
13.3145 ng/ml
Standard Deviation 18.82955
|
|
CsA Whole Blood Concentrations and CsA Whole Blood Trough Levels
1 hour
|
117.8030 ng/ml
Standard Deviation NA
Standard Deviation is not calculable for 1 participant
|
19.4395 ng/ml
Standard Deviation 18.15638
|
14.0835 ng/ml
Standard Deviation 19.91708
|
|
CsA Whole Blood Concentrations and CsA Whole Blood Trough Levels
1.5 hours
|
115.4350 ng/ml
Standard Deviation NA
Standard Deviation is not calculable for 1 participant
|
16.0300 ng/ml
Standard Deviation 13.34876
|
13.0425 ng/ml
Standard Deviation 18.44488
|
|
CsA Whole Blood Concentrations and CsA Whole Blood Trough Levels
2 hours
|
67.0700 ng/ml
Standard Deviation 71.46587
|
13.4045 ng/ml
Standard Deviation 10.80530
|
10.9615 ng/ml
Standard Deviation 15.50190
|
|
CsA Whole Blood Concentrations and CsA Whole Blood Trough Levels
4 hours
|
33.3425 ng/ml
Standard Deviation 35.73506
|
8.3950 ng/ml
Standard Deviation 8.09920
|
7.6615 ng/ml
Standard Deviation 10.83500
|
|
CsA Whole Blood Concentrations and CsA Whole Blood Trough Levels
Whole Blood Trough Levels - Week 2
|
48.6725 ng/ml
Standard Deviation 64.65148
|
4.6365 ng/ml
Standard Deviation 3.62534
|
6.0500 ng/ml
Standard Deviation 8.55599
|
|
CsA Whole Blood Concentrations and CsA Whole Blood Trough Levels
Whole Blood Trough Levels - Week 4
|
16.2465 ng/ml
Standard Deviation 17.33048
|
16.8475 ng/ml
Standard Deviation 21.28745
|
6.3000 ng/ml
Standard Deviation 8.90955
|
|
CsA Whole Blood Concentrations and CsA Whole Blood Trough Levels
Whole Blood Trough Levels - Week 8
|
18.7280 ng/ml
Standard Deviation 26.48539
|
9.0405 ng/ml
Standard Deviation 3.16855
|
4.9500 ng/ml
Standard Deviation 7.00036
|
|
CsA Whole Blood Concentrations and CsA Whole Blood Trough Levels
Whole Blood Trough Levels - Week 12
|
23.0195 ng/ml
Standard Deviation 32.55449
|
0.0000 ng/ml
Standard Deviation NA
Standard Deviation is not calculable for 1 participant
|
4.9500 ng/ml
Standard Deviation 7.00036
|
Adverse Events
L-CsA 10 mg Plus Standard of Care
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
L-CsA 5 mg Plus Standard of Care
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Liposomal Placebo Plus Standard of Care
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
L-CsA 10 mg Plus Standard of Care
n=2 participants at risk
Liposomal Cyclosporine A 10 mg (10 mg/2.5 mL) bid, once in the morning and once in the evening, for up to 12 weeks.
The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 8 to 13 minutes for the 0- and 10-mg doses.
Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
L-CsA 5 mg Plus Standard of Care
n=2 participants at risk
Liposomal Cyclosporine A 5 mg (5 mg/1.25 mL) bid, once in the morning and once in the evening, for up to 12 weeks. The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 5 to 10 minutes for the 5-mg dose.
Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
Liposomal Placebo Plus Standard of Care
n=2 participants at risk
Liposomal Placebo 2.5 mL (0 mg L-CsA/2.5 mL) bid, once in the morning and once in the evening, for up to 12 weeks.
The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 8 to 13 minutes for the 0- and 10-mg doses. Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
moderate acute respiratory failure
|
50.0%
1/2 • Number of events 1 • Throughout the complete clinical trial period, i.e. up to week 14 (visit 6 / EoS).
Please note that if a patient has multiple occurrences of an AE, the patient is presented only once in the respective patient count
|
0.00%
0/2 • Throughout the complete clinical trial period, i.e. up to week 14 (visit 6 / EoS).
Please note that if a patient has multiple occurrences of an AE, the patient is presented only once in the respective patient count
|
0.00%
0/2 • Throughout the complete clinical trial period, i.e. up to week 14 (visit 6 / EoS).
Please note that if a patient has multiple occurrences of an AE, the patient is presented only once in the respective patient count
|
Other adverse events
| Measure |
L-CsA 10 mg Plus Standard of Care
n=2 participants at risk
Liposomal Cyclosporine A 10 mg (10 mg/2.5 mL) bid, once in the morning and once in the evening, for up to 12 weeks.
The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 8 to 13 minutes for the 0- and 10-mg doses.
Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
L-CsA 5 mg Plus Standard of Care
n=2 participants at risk
Liposomal Cyclosporine A 5 mg (5 mg/1.25 mL) bid, once in the morning and once in the evening, for up to 12 weeks. The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 5 to 10 minutes for the 5-mg dose.
Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
Liposomal Placebo Plus Standard of Care
n=2 participants at risk
Liposomal Placebo 2.5 mL (0 mg L-CsA/2.5 mL) bid, once in the morning and once in the evening, for up to 12 weeks.
The inhalations were scheduled to be taken approximately 12 hours (but not less than 6 hours) apart, eg, at 08:00 and 20:00 each day. Nebulization time per inhalation dose was approximately 8 to 13 minutes for the 0- and 10-mg doses. Standard of care included prophylaxis against common opportunistic infections, immunosuppression, and any other chronic medication
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
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
50.0%
1/2 • Number of events 1 • Throughout the complete clinical trial period, i.e. up to week 14 (visit 6 / EoS).
Please note that if a patient has multiple occurrences of an AE, the patient is presented only once in the respective patient count
|
50.0%
1/2 • Number of events 1 • Throughout the complete clinical trial period, i.e. up to week 14 (visit 6 / EoS).
Please note that if a patient has multiple occurrences of an AE, the patient is presented only once in the respective patient count
|
50.0%
1/2 • Number of events 1 • Throughout the complete clinical trial period, i.e. up to week 14 (visit 6 / EoS).
Please note that if a patient has multiple occurrences of an AE, the patient is presented only once in the respective patient count
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/2 • Throughout the complete clinical trial period, i.e. up to week 14 (visit 6 / EoS).
Please note that if a patient has multiple occurrences of an AE, the patient is presented only once in the respective patient count
|
50.0%
1/2 • Number of events 1 • Throughout the complete clinical trial period, i.e. up to week 14 (visit 6 / EoS).
Please note that if a patient has multiple occurrences of an AE, the patient is presented only once in the respective patient count
|
50.0%
1/2 • Number of events 1 • Throughout the complete clinical trial period, i.e. up to week 14 (visit 6 / EoS).
Please note that if a patient has multiple occurrences of an AE, the patient is presented only once in the respective patient count
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/2 • Throughout the complete clinical trial period, i.e. up to week 14 (visit 6 / EoS).
Please note that if a patient has multiple occurrences of an AE, the patient is presented only once in the respective patient count
|
50.0%
1/2 • Number of events 1 • Throughout the complete clinical trial period, i.e. up to week 14 (visit 6 / EoS).
Please note that if a patient has multiple occurrences of an AE, the patient is presented only once in the respective patient count
|
0.00%
0/2 • Throughout the complete clinical trial period, i.e. up to week 14 (visit 6 / EoS).
Please note that if a patient has multiple occurrences of an AE, the patient is presented only once in the respective patient count
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
50.0%
1/2 • Number of events 1 • Throughout the complete clinical trial period, i.e. up to week 14 (visit 6 / EoS).
Please note that if a patient has multiple occurrences of an AE, the patient is presented only once in the respective patient count
|
0.00%
0/2 • Throughout the complete clinical trial period, i.e. up to week 14 (visit 6 / EoS).
Please note that if a patient has multiple occurrences of an AE, the patient is presented only once in the respective patient count
|
0.00%
0/2 • Throughout the complete clinical trial period, i.e. up to week 14 (visit 6 / EoS).
Please note that if a patient has multiple occurrences of an AE, the patient is presented only once in the respective patient count
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
50.0%
1/2 • Number of events 1 • Throughout the complete clinical trial period, i.e. up to week 14 (visit 6 / EoS).
Please note that if a patient has multiple occurrences of an AE, the patient is presented only once in the respective patient count
|
0.00%
0/2 • Throughout the complete clinical trial period, i.e. up to week 14 (visit 6 / EoS).
Please note that if a patient has multiple occurrences of an AE, the patient is presented only once in the respective patient count
|
0.00%
0/2 • Throughout the complete clinical trial period, i.e. up to week 14 (visit 6 / EoS).
Please note that if a patient has multiple occurrences of an AE, the patient is presented only once in the respective patient count
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place