Trial Outcomes & Findings for Efficacy + Safety of Liposome Cyclosporine A to Treat Bronchiolitis Obliterans Post Double Lung Transplant (BOSTON-2) (NCT NCT03656926)

Last Updated: 2025-07-24

Results Overview

FEV1 is the Forced Expiratory Volume in One Second. The FEV1 data collected from the on-site COMPACTTM spirometer were to be considered primary, while data collected with the In2itiveTM home spirometer were to be used for supportive analyses.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

169 participants

Primary outcome timeframe

Week 48

Results posted on

2025-07-24

Participant Flow

The COVID-19 pandemic impacted the conduct of the study. Based on the evolution of the outbreak and in accordance with country- and site-specific determinations, recruitment was put on hold starting on 20 March 2020. Recruitment was subsequently resumed in Quarter 3 2020. COVID- 19 might have affected the results for different reasons including changes in infection rate and type, quarantining, social distancing, and other considerations linked to different ways each site managed the pandemic.

Participant milestones

Participant milestones
Measure	L-CsA Treatment Plus SoC Liposomal Cyclosporine A (L-CsA) 10 mg twice daily for 48 weeks, plus Standard of Care Therapy Liposomal Cyclosporine A: This formulation is developed for inhalation use and delivered via the PARI eFlow® Device, which is a new technology of nebulizing liquid drugs with a perforated vibrating membrane resulting in an aerosol with a low ballistic momentum and a high percentage of droplets in a respirable size range of 3-5 μm. The L-CsA was administered as 10 mg/2.4 mL inhalation via the PARI eFlow device BID (morning/evening, approximately 12 hours apart) for 48 weeks. Nebulization time per inhalation dose was approximately 6 to 17 minutes. Patients received training on the use of the device and the first dose of L-CsA was self-administered by each patient under the supervision of trained personnel. In addition, during all subsequent scheduled visits the L-CsA inhalation was self-administered by the patient and under the supervision of trained study personnel.	Standard of Care This is a maintenance regimen of immunosuppressive agents Standard of Care: Standard of Care Therapy (SoC). The SoC included maintenance immunosuppressive medication including tacrolimus, a second agent such as but not limited to MMF or azathioprine, and a systemic corticosteroid such as prednisone as third agent; but also a prophylaxis against common opportunistic infections, and all other necessary medications and therapies for the optimal care of the patient. This also included vaccination against COVID-19 All changes in concurrent treatment or medication were administered according to site's SoC. The regimen must be stable within 4 weeks prior to randomization with respect to the therapeutic agents. Patients receiving azithromycin for prophylaxis or treatment of BOS, should be on a stable regimen for a least 4-weeks prior to randomization and continued to receive azithromycin during the trial as deemed appropriate by the investigator.
Overall Study STARTED	84	85
Overall Study Full Analysis Set	84	85
Overall Study Safety Analysis Set	84	85
Overall Study Per Protocol Set	46	70
Overall Study COMPLETED	69	79
Overall Study NOT COMPLETED	15	6

Reasons for withdrawal

Reasons for withdrawal
Measure	L-CsA Treatment Plus SoC Liposomal Cyclosporine A (L-CsA) 10 mg twice daily for 48 weeks, plus Standard of Care Therapy Liposomal Cyclosporine A: This formulation is developed for inhalation use and delivered via the PARI eFlow® Device, which is a new technology of nebulizing liquid drugs with a perforated vibrating membrane resulting in an aerosol with a low ballistic momentum and a high percentage of droplets in a respirable size range of 3-5 μm. The L-CsA was administered as 10 mg/2.4 mL inhalation via the PARI eFlow device BID (morning/evening, approximately 12 hours apart) for 48 weeks. Nebulization time per inhalation dose was approximately 6 to 17 minutes. Patients received training on the use of the device and the first dose of L-CsA was self-administered by each patient under the supervision of trained personnel. In addition, during all subsequent scheduled visits the L-CsA inhalation was self-administered by the patient and under the supervision of trained study personnel.	Standard of Care This is a maintenance regimen of immunosuppressive agents Standard of Care: Standard of Care Therapy (SoC). The SoC included maintenance immunosuppressive medication including tacrolimus, a second agent such as but not limited to MMF or azathioprine, and a systemic corticosteroid such as prednisone as third agent; but also a prophylaxis against common opportunistic infections, and all other necessary medications and therapies for the optimal care of the patient. This also included vaccination against COVID-19 All changes in concurrent treatment or medication were administered according to site's SoC. The regimen must be stable within 4 weeks prior to randomization with respect to the therapeutic agents. Patients receiving azithromycin for prophylaxis or treatment of BOS, should be on a stable regimen for a least 4-weeks prior to randomization and continued to receive azithromycin during the trial as deemed appropriate by the investigator.
Overall Study Adverse Event	5	4
Overall Study Withdrawal by Subject	7	2
Overall Study Screen fail after randomization	1	0
Overall Study PI decision due to patient condition	1	0
Overall Study Patient unresponsiveness	1	0

Baseline Characteristics

Efficacy + Safety of Liposome Cyclosporine A to Treat Bronchiolitis Obliterans Post Double Lung Transplant (BOSTON-2)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	L-CsA Treatment Plus SoC - SAF n=84 Participants Liposomal Cyclosporine A (L-CsA) 10 mg twice daily for 48 weeks, plus Standard of Care Therapy Liposomal Cyclosporine A: This formulation is developed for inhalation use and delivered via the PARI eFlow® Device, which is a new technology of nebulizing liquid drugs with a perforated vibrating membrane resulting in an aerosol with a low ballistic momentum and a high percentage of droplets in a respirable size range of 3-5 μm. The L-CsA was administered as 10 mg/2.4 mL inhalation via the PARI eFlow device BID (morning/evening, approximately 12 hours apart) for 48 weeks. Nebulization time per inhalation dose was approximately 6 to 17 minutes. Patients received training on the use of the device and the first dose of L-CsA was self-administered by each patient under the supervision of trained personnel. In addition, during all subsequent scheduled visits the L-CsA inhalation was self-administered by the patient and under the supervision of trained study personnel.	Standard of Care - SAF n=85 Participants This is a maintenance regimen of immunosuppressive agents Standard of Care: Standard of Care Therapy (SoC). The SoC included maintenance immunosuppressive medication including tacrolimus, a second agent such as but not limited to MMF or azathioprine, and a systemic corticosteroid such as prednisone as third agent; but also a prophylaxis against common opportunistic infections, and all other necessary medications and therapies for the optimal care of the patient. This also included vaccination against COVID-19 All changes in concurrent treatment or medication were administered according to site's SoC. The regimen must be stable within 4 weeks prior to randomization with respect to the therapeutic agents. Patients receiving azithromycin for prophylaxis or treatment of BOS, should be on a stable regimen for a least 4-weeks prior to randomization and continued to receive azithromycin during the trial as deemed appropriate by the investigator.	Total n=169 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
Age, Categorical Between 18 and 65 years	58 Participants n=5 Participants	64 Participants n=7 Participants	122 Participants n=5 Participants
Age, Categorical >=65 years	26 Participants n=5 Participants	21 Participants n=7 Participants	47 Participants n=5 Participants
Age, Continuous	56.5 years STANDARD_DEVIATION 12.69 • n=5 Participants	56.2 years STANDARD_DEVIATION 10.82 • n=7 Participants	56.3 years STANDARD_DEVIATION 11.75 • n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants	42 Participants n=7 Participants	76 Participants n=5 Participants
Sex: Female, Male Male	50 Participants n=5 Participants	43 Participants n=7 Participants	93 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	70 Participants n=5 Participants	71 Participants n=7 Participants	141 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	75 Participants n=5 Participants	70 Participants n=7 Participants	145 Participants n=5 Participants
Race (NIH/OMB) More than one race	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment Austria	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment Belgium	4 participants n=5 Participants	2 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment United States	30 participants n=5 Participants	31 participants n=7 Participants	61 participants n=5 Participants
Region of Enrollment Denmark	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment United Kingdom	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment Israel	4 participants n=5 Participants	1 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment France	4 participants n=5 Participants	8 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment Germany	15 participants n=5 Participants	19 participants n=7 Participants	34 participants n=5 Participants
Region of Enrollment Spain	21 participants n=5 Participants	15 participants n=7 Participants	36 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 48

Population: Full analysis set: The FAS was defined as all randomized patients. Patients were analyzed according to the treatment group to which they were randomized. Please note that N = number of patients in analysis set (N=84 for L-CSA + SoC and N=85 for SoC alone); n = number of patients with data available (n=64 for L-CSA + SoC and n=80 for SoC alone)

Outcome measures

Outcome measures
Measure	L-CsA Treatment Plus SoC - FAS n=64 Participants Liposomal Cyclosporine A (L-CsA) 10 mg twice daily for 48 weeks, plus Standard of Care Therapy Liposomal Cyclosporine A: This formulation is developed for inhalation use and delivered via the PARI eFlow® Device, which is a new technology of nebulizing liquid drugs with a perforated vibrating membrane resulting in an aerosol with a low ballistic momentum and a high percentage of droplets in a respirable size range of 3-5 μm. The L-CsA was administered as 10 mg/2.4 mL inhalation via the PARI eFlow device BID (morning/evening, approximately 12 hours apart) for 48 weeks. Nebulization time per inhalation dose was approximately 6 to 17 minutes. Patients received training on the use of the device and the first dose of L-CsA was self-administered by each patient under the supervision of trained personnel. In addition, during all subsequent scheduled visits the L-CsA inhalation was self-administered by the patient and under the supervision of trained study personnel.	Standard of Care - FAS n=80 Participants This is a maintenance regimen of immunosuppressive agents Standard of Care: Standard of Care Therapy (SoC). The SoC included maintenance immunosuppressive medication including tacrolimus, a second agent such as but not limited to MMF or azathioprine, and a systemic corticosteroid such as prednisone as third agent; but also a prophylaxis against common opportunistic infections, and all other necessary medications and therapies for the optimal care of the patient. This also included vaccination against COVID-19 All changes in concurrent treatment or medication were administered according to site's SoC. The regimen must be stable within 4 weeks prior to randomization with respect to the therapeutic agents. Patients receiving azithromycin for prophylaxis or treatment of BOS, should be on a stable regimen for a least 4-weeks prior to randomization and continued to receive azithromycin during the trial as deemed appropriate by the investigator.
Mean Change in FEV1 (mL) From Baseline to Week 48	-0.096 mL Standard Error 0.1120	-0.067 mL Standard Error 0.1147

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline through study completion (52 weeks)

Population: SAF: The SAF was defined as all randomized patients receiving SoC and/or at least one dose of L-CsA, independently of the treatment allocation at randomization. Independently of the treatment allocation at randomization, patients were analyzed according to the treatment they actually received.

An untoward medical occurrence after exposure to a medicine, which is not necessarily caused by that medicine.

Outcome measures

Outcome measures
Measure	L-CsA Treatment Plus SoC - FAS n=84 Participants Liposomal Cyclosporine A (L-CsA) 10 mg twice daily for 48 weeks, plus Standard of Care Therapy Liposomal Cyclosporine A: This formulation is developed for inhalation use and delivered via the PARI eFlow® Device, which is a new technology of nebulizing liquid drugs with a perforated vibrating membrane resulting in an aerosol with a low ballistic momentum and a high percentage of droplets in a respirable size range of 3-5 μm. The L-CsA was administered as 10 mg/2.4 mL inhalation via the PARI eFlow device BID (morning/evening, approximately 12 hours apart) for 48 weeks. Nebulization time per inhalation dose was approximately 6 to 17 minutes. Patients received training on the use of the device and the first dose of L-CsA was self-administered by each patient under the supervision of trained personnel. In addition, during all subsequent scheduled visits the L-CsA inhalation was self-administered by the patient and under the supervision of trained study personnel.	Standard of Care - FAS n=85 Participants This is a maintenance regimen of immunosuppressive agents Standard of Care: Standard of Care Therapy (SoC). The SoC included maintenance immunosuppressive medication including tacrolimus, a second agent such as but not limited to MMF or azathioprine, and a systemic corticosteroid such as prednisone as third agent; but also a prophylaxis against common opportunistic infections, and all other necessary medications and therapies for the optimal care of the patient. This also included vaccination against COVID-19 All changes in concurrent treatment or medication were administered according to site's SoC. The regimen must be stable within 4 weeks prior to randomization with respect to the therapeutic agents. Patients receiving azithromycin for prophylaxis or treatment of BOS, should be on a stable regimen for a least 4-weeks prior to randomization and continued to receive azithromycin during the trial as deemed appropriate by the investigator.
Count of Participants With at Least One Adverse Event (AE) with any TEAE	73 Participants	77 Participants
Count of Participants With at Least One Adverse Event (AE) with any TEAE Leading to discontinuation of study treatment	12 Participants	0 Participants
Count of Participants With at Least One Adverse Event (AE) with any TEAE Leading to study discontinuation	5 Participants	3 Participants
Count of Participants With at Least One Adverse Event (AE) with any TEAE Leading to death	2 Participants	4 Participants
Count of Participants With at Least One Adverse Event (AE) with any TEAE mild	66 Participants	68 Participants
Count of Participants With at Least One Adverse Event (AE) with any TEAE moderate	50 Participants	56 Participants
Count of Participants With at Least One Adverse Event (AE) with any TEAE severe	21 Participants	18 Participants
Count of Participants With at Least One Adverse Event (AE) with any study treatment-related TEAE	39 Participants	0 Participants
Count of Participants With at Least One Adverse Event (AE) with any serious TEAE	46 Participants	44 Participants

Adverse Events

L-CsA Treatment Plus SoC - SAF

Serious events: 46 serious events

Other events: 73 other events

Deaths: 2 deaths

Standard of Care - SAF

Serious events: 44 serious events

Other events: 77 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

Enrica Bucchioni, M.D., PhD, Global Clinical Development Head

Zambon S.p.A.

Phone: +39 02 665241

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	L-CsA Treatment Plus SoC - SAF n=84 participants at risk Liposomal Cyclosporine A (L-CsA) 10 mg twice daily for 48 weeks, plus Standard of Care Therapy Liposomal Cyclosporine A: This formulation is developed for inhalation use and delivered via the PARI eFlow® Device, which is a new technology of nebulizing liquid drugs with a perforated vibrating membrane resulting in an aerosol with a low ballistic momentum and a high percentage of droplets in a respirable size range of 3-5 μm. The L-CsA was administered as 10 mg/2.4 mL inhalation via the PARI eFlow device BID (morning/evening, approximately 12 hours apart) for 48 weeks. Nebulization time per inhalation dose was approximately 6 to 17 minutes. Patients received training on the use of the device and the first dose of L-CsA was self-administered by each patient under the supervision of trained personnel. In addition, during all subsequent scheduled visits the L-CsA inhalation was self-administered by the patient and under the supervision of trained study personnel.	Standard of Care - SAF n=85 participants at risk This is a maintenance regimen of immunosuppressive agents Standard of Care: Standard of Care Therapy (SoC). The SoC included maintenance immunosuppressive medication including tacrolimus, a second agent such as but not limited to MMF or azathioprine, and a systemic corticosteroid such as prednisone as third agent; but also a prophylaxis against common opportunistic infections, and all other necessary medications and therapies for the optimal care of the patient. This also included vaccination against COVID-19 All changes in concurrent treatment or medication were administered according to site's SoC. The regimen must be stable within 4 weeks prior to randomization with respect to the therapeutic agents. Patients receiving azithromycin for prophylaxis or treatment of BOS, should be on a stable regimen for a least 4-weeks prior to randomization and continued to receive azithromycin during the trial as deemed appropriate by the investigator.
Infections and infestations COVID-19	27.4% 23/84 • Number of events 23 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.	24.7% 21/85 • Number of events 23 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.
Infections and infestations COVID-19 pneumonia	6.0% 5/84 • Number of events 5 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.	1.2% 1/85 • Number of events 1 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.
Infections and infestations Bronchitis	3.6% 3/84 • Number of events 3 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.	1.2% 1/85 • Number of events 1 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.
Infections and infestations Gastroenteritis	3.6% 3/84 • Number of events 3 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.	0.00% 0/85 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.
Infections and infestations Pneumonia	3.6% 3/84 • Number of events 3 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.	3.5% 3/85 • Number of events 6 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.
Infections and infestations Parainfluenzae virus infection	1.2% 1/84 • Number of events 1 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.	1.2% 1/85 • Number of events 1 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.
Infections and infestations Urinary tract infection	0.00% 0/84 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.	2.4% 2/85 • Number of events 2 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	2.4% 2/84 • Number of events 2 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.	1.2% 1/85 • Number of events 1 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.4% 2/84 • Number of events 3 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.	1.2% 1/85 • Number of events 1 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.4% 2/84 • Number of events 2 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.	1.2% 1/85 • Number of events 1 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.4% 2/84 • Number of events 2 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.	3.5% 3/85 • Number of events 4 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/84 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.	2.4% 2/85 • Number of events 2 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.
Renal and urinary disorders Acute kidney injury	6.0% 5/84 • Number of events 5 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.	2.4% 2/85 • Number of events 2 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.
Gastrointestinal disorders Nausea	1.2% 1/84 • Number of events 1 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.	1.2% 1/85 • Number of events 1 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.
Gastrointestinal disorders Vomiting	1.2% 1/84 • Number of events 1 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.	1.2% 1/85 • Number of events 1 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.
General disorders Multiple organ dysfunction syndrome	2.4% 2/84 • Number of events 2 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.	0.00% 0/85 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.
General disorders Disease progression	0.00% 0/84 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.	2.4% 2/85 • Number of events 2 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.
Immune system disorders Transplant rejection	2.4% 2/84 • Number of events 2 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.	2.4% 2/85 • Number of events 2 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.
Metabolism and nutrition disorders Dehydration	1.2% 1/84 • Number of events 1 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.	1.2% 1/85 • Number of events 1 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bowen's disease	1.2% 1/84 • Number of events 1 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.	1.2% 1/85 • Number of events 2 • From baseline throughout the study, till week 52. Serious TEAEs by System Organ Class and Preferred Term in Safety Analysis Set are Reported by at Least 2 Patients Overall. Non serious adverse events are reported with a 0% threshold on the same set.