Trial Outcomes & Findings for Aerosol Liposomal Cyclosporine for Chronic Rejection in Lung Transplant Recipients (NCT NCT01650545)

NCT ID: NCT01650545

Last Updated: 2023-06-01

Results Overview

Treatment failure defined as: BOS progression (\> 20% decline lung function), re-transplant, or death

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

21 participants

Primary outcome timeframe

approximately 1 year

Results posted on

2023-06-01

Participant Flow

Participant milestones

Participant milestones
Measure	Liposomal Aerosol Cyclosporine Arm 1) Aerosol liposomal cyclosporine Open label randomized trial using experimental inhalational therapy with liposomal aerosol cyclosporine in addition to standard immune suppression (tacrolimus , mycophenolate mofetil and prednisone) for 6 month duration at inhalational doses (5mg and 10 mg bid), to be defined by transplant type respectively (single, double lung transplant ) Liposomal aerosol cyclosporine: inhaled form of immune suppression standard immune suppression, oral: conventional drug	Conventional Oral Immune Suppression Arm 2) Standard immune suppression consisting of typical oral immune suppression for lung transplant recipients typically tacrolimus, mycophenolate mofetil and prednisone standard immune suppression, oral: conventional drug
Overall Study STARTED	11	10
Overall Study COMPLETED	11	10
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Aerosol Liposomal Cyclosporine for Chronic Rejection in Lung Transplant Recipients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Liposomal Aerosol Cyclosporine n=11 Participants Arm 1) Aerosol liposomal cyclosporine Open label randomized trial using experimental inhalational therapy with liposomal aerosol cyclosporine in addition to standard immune suppression (tacrolimus , mycophenolate mofetil and prednisone) for 6 month duration at inhalational doses (5mg and 10 mg bid), to be defined by transplant type respectively (single, double lung transplant ) Liposomal aerosol cyclosporine: inhaled form of immune suppression standard immune suppression, oral: conventional drug	Conventional Oral Immune Suppression n=10 Participants Arm 2) Standard immune suppression consisting of typical oral immune suppression for lung transplant recipients typically tacrolimus, mycophenolate mofetil and prednisone standard immune suppression, oral: conventional drug	Total n=21 Participants Total of all reporting groups
Region of Enrollment United States	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Age, Continuous	59.1 years n=5 Participants	63.8 years n=7 Participants	61.3 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	8 Participants n=7 Participants	14 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: approximately 1 year

Treatment failure defined as: BOS progression (\> 20% decline lung function), re-transplant, or death

Outcome measures

Outcome measures
Measure	Liposomal Aerosol Cyclosporine n=11 Participants Arm 1) Aerosol liposomal cyclosporine Open label randomized trial using experimental inhalational therapy with liposomal aerosol cyclosporine in addition to standard immune suppression (tacrolimus , mycophenolate mofetil and prednisone) for 6 month duration at inhalational doses (5mg and 10 mg bid), to be defined by transplant type respectively (single, double lung transplant ) Liposomal aerosol cyclosporine: inhaled form of immune suppression standard immune suppression, oral: conventional drug	Conventional Oral Immune Suppression n=10 Participants Arm 2) Standard immune suppression consisting of typical oral immune suppression for lung transplant recipients typically tacrolimus, mycophenolate mofetil and prednisone standard immune suppression, oral: conventional drug
Number Of Participants With Chronic Rejection Who Met Primary Combined End-point	2 Participants	5 Participants

SECONDARY outcome

Timeframe: baseline to approximately 1 year

Multiple cytokines were assessed as markers of lung inflammation that may be used in addition to biopsy data, collected per patient as clinically indicated during the follow-up interval. Values are reported as mean change from baseline in each group, per week

Outcome measures

Outcome measures
Measure	Liposomal Aerosol Cyclosporine n=11 Participants Arm 1) Aerosol liposomal cyclosporine Open label randomized trial using experimental inhalational therapy with liposomal aerosol cyclosporine in addition to standard immune suppression (tacrolimus , mycophenolate mofetil and prednisone) for 6 month duration at inhalational doses (5mg and 10 mg bid), to be defined by transplant type respectively (single, double lung transplant ) Liposomal aerosol cyclosporine: inhaled form of immune suppression standard immune suppression, oral: conventional drug	Conventional Oral Immune Suppression n=10 Participants Arm 2) Standard immune suppression consisting of typical oral immune suppression for lung transplant recipients typically tacrolimus, mycophenolate mofetil and prednisone standard immune suppression, oral: conventional drug
Cytokine Analysis From BAL Fluid in Lung IFN-gamma	0.5 pg/mL Interval -0.1 to 1.0	0 pg/mL Interval -0.4 to 0.5
Cytokine Analysis From BAL Fluid in Lung lL-1beta	-2 pg/mL Interval -9.3 to 5.3	3.3 pg/mL Interval -4.3 to 10.9
Cytokine Analysis From BAL Fluid in Lung IL-2	-0.9 pg/mL Interval -1.5 to 0.3	-0.3 pg/mL Interval -0.9 to 0.3
Cytokine Analysis From BAL Fluid in Lung IL-6	-2.0 pg/mL Interval -7.9 to 3.9	6.3 pg/mL Interval 1.2 to 11.5
Cytokine Analysis From BAL Fluid in Lung IL-8	13.6 pg/mL Interval -20.3 to 47.4	37.5 pg/mL Interval 2.1 to 72.9
Cytokine Analysis From BAL Fluid in Lung IL-10	0.1 pg/mL Interval -0.7 to 0.9	0.1 pg/mL Interval -1.3 to 1.5
Cytokine Analysis From BAL Fluid in Lung IL-17	0.4 pg/mL Interval -0.1 to 0.8	0.1 pg/mL Interval -0.5 to 0.8
Cytokine Analysis From BAL Fluid in Lung TNF-alpha	1.9 pg/mL Interval -8.6 to 12.4	-1.7 pg/mL Interval -8.0 to 4.7

SECONDARY outcome

Timeframe: 5 years

Number of participants surviving at 5 year follow-up

Outcome measures

Outcome measures
Measure	Liposomal Aerosol Cyclosporine n=11 Participants Arm 1) Aerosol liposomal cyclosporine Open label randomized trial using experimental inhalational therapy with liposomal aerosol cyclosporine in addition to standard immune suppression (tacrolimus , mycophenolate mofetil and prednisone) for 6 month duration at inhalational doses (5mg and 10 mg bid), to be defined by transplant type respectively (single, double lung transplant ) Liposomal aerosol cyclosporine: inhaled form of immune suppression standard immune suppression, oral: conventional drug	Conventional Oral Immune Suppression n=10 Participants Arm 2) Standard immune suppression consisting of typical oral immune suppression for lung transplant recipients typically tacrolimus, mycophenolate mofetil and prednisone standard immune suppression, oral: conventional drug
Overall Survival at 5 Years Follow-up	5 Participants	0 Participants

Adverse Events

Liposomal Aerosol Cyclosporine

Serious events: 8 serious events

Other events: 11 other events

Deaths: 6 deaths

Conventional Oral Immune Suppression

Serious events: 8 serious events

Other events: 10 other events

Deaths: 10 deaths

Serious adverse events

Other adverse events

Additional Information

Aldo Tullio Iacono

University of Maryland

Phone: 410 328 4351

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Liposomal Aerosol Cyclosporine n=11 participants at risk Arm 1) Aerosol liposomal cyclosporine Open label randomized trial using experimental inhalational therapy with liposomal aerosol cyclosporine in addition to standard immune suppression (tacrolimus , mycophenolate mofetil and prednisone) for 6 month duration at inhalational doses (5mg and 10 mg bid), to be defined by transplant type respectively (single, double lung transplant ) Liposomal aerosol cyclosporine: inhaled form of immune suppression standard immune suppression, oral: conventional drug	Conventional Oral Immune Suppression n=10 participants at risk Arm 2) Standard immune suppression consisting of typical oral immune suppression for lung transplant recipients typically tacrolimus, mycophenolate mofetil and prednisone standard immune suppression, oral: conventional drug
Cardiac disorders Atrial flutter	9.1% 1/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	0.00% 0/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Cardiac disorders Congestive heart failure	0.00% 0/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	10.0% 1/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Cardiac disorders Myocardial infarction	0.00% 0/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	10.0% 1/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Cardiac disorders Rapid atrial fibrillation	0.00% 0/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	10.0% 1/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Gastrointestinal disorders Cholelithiasis	9.1% 1/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	0.00% 0/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Gastrointestinal disorders Diarrhea	9.1% 1/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	0.00% 0/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Gastrointestinal disorders Gastroenteritis	9.1% 1/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	0.00% 0/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Gastrointestinal disorders Melena	0.00% 0/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	20.0% 2/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
General disorders Weakness	0.00% 0/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	10.0% 1/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Immune system disorders Acute graft rejection	27.3% 3/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	10.0% 1/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Infections and infestations Bacteremia	9.1% 1/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	0.00% 0/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Infections and infestations Bronchitis	9.1% 1/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	0.00% 0/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Infections and infestations Herpes zoster exacerbation	9.1% 1/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	0.00% 0/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Infections and infestations Influenza	18.2% 2/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	0.00% 0/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Infections and infestations Pneumonia	9.1% 1/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	40.0% 4/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Infections and infestations Pyrexia	0.00% 0/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	10.0% 1/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Infections and infestations Respiratory syncytial virus	0.00% 0/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	30.0% 3/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Infections and infestations Rhinovirus	0.00% 0/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	10.0% 1/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Infections and infestations Urinary tract infection	9.1% 1/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	0.00% 0/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Metabolism and nutrition disorders Hypoglycemia	9.1% 1/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	0.00% 0/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Respiratory, thoracic and mediastinal disorders Aspiration	9.1% 1/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	0.00% 0/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Respiratory, thoracic and mediastinal disorders Dyspnea	36.4% 4/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	40.0% 4/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Respiratory, thoracic and mediastinal disorders Hypoxic respiratory failure	9.1% 1/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	20.0% 2/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Respiratory, thoracic and mediastinal disorders Pneumomediastinum	0.00% 0/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	10.0% 1/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	9.1% 1/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	10.0% 1/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Skin and subcutaneous tissue disorders Squamous cell carcinoma (scalp/left cheek)	9.1% 1/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	0.00% 0/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.
Vascular disorders Deep vein thrombosis	9.1% 1/11 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.	0.00% 0/10 • Serious and non-serious adverse events monitored for one year as described in the IND. All cause mortality monitored out to 5 years.