Study of Cyclosporine Inhalation Solution (CIS) in Improving Bronchiolitis Obliterans Syndrome-Free Survival Following Lung Transplantation - Full Text View

Purpose

A Phase III, multi-center, randomized, controlled study designed to demonstrate the efficacy and safety of Cyclosporine Inhalation Solution (CIS)in improving survival and preventing bronchiolitis obliterans syndrome (BOS) when given prophylactically to lung transplant recipients in addition to their standard immunosuppressive regimen.

Condition	Intervention	Phase
Lung Transplant	Drug: Cyclosporine Inhalation Solution (CIS)	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	A Multi-Center, Randomized, Controlled Study to Demonstrate the Efficacy and Safety of Cyclosporine Inhalation Solution (CIS) in Improving Bronchiolitis Obliterans Syndrome-Free Survival Following Lung Transplantation

Resource links provided by NLM:

MedlinePlus related topics: Lung Transplantation

Drug Information available for: Cyclosporine

U.S. FDA Resources

Further study details as provided by APT Pharmaceuticals, Inc.:

Primary Outcome Measures:

Duration of BOS-free survival. Other causes for the decline should be excluded by bronchoscopy and other diagnostic testing performed at the discretion of the investigator. The diagnosis of BOS will be determined by the Outcomes Committee [ Time Frame: Assessed when symptoms of syndrome present ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pulmonary function as measured by mean FEV1 percent predicted at 2 years after randomization [ Time Frame: From study initiation through 2+ years after randomization ] [ Designated as safety issue: No ]
All cause mortality [ Time Frame: From study initiation through 2+ years after randomization ] [ Designated as safety issue: No ]
Duration of event-free survival, corresponding to the length of time between date of randomization and either death or the occurrence of serious bacterial and viral infections that start in the lungs (defined by reporting of a SAE) [ Time Frame: From study initiation through 2+ year after randomzation ] [ Designated as safety issue: No ]

Enrollment:	284
Study Start Date:	September 2008
Study Completion Date:	November 2011
Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: CIS CIS in addition to standard immunosuppressive regimen.	Drug: Cyclosporine Inhalation Solution (CIS) Cyclosporine (USP) Inhalation Solution; 300mg/4.8 mL in propylene glycol (USP) at a concentration of 62.5 mg/mL; 3 times a week for study duration (up to 3 years) Other Name: Cyclosporine
No Intervention: SOC Standard of care (SOC) therapy for lung transplant recipients

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

A recipient of a single or double lung transplant (including heart-lung transplant)
Age 18 years or older
Able to produce a forced expiratory volume in one second (FEV1) of greater than one liter at randomization
Eligible subjects must be enrolled within 70 days after receiving a lung transplant
Clinical status sufficiently stable to enable routine post-transplant bronchoscopy with bronchoalveolar lavage (BAL) and chest X-ray (or equivalent i.e., chest computerized tomogram (CT)) prior to screening

Exclusion Criteria:

Lung re-transplantation
Documented allergy to propylene glycol and/or cyclosporine
Documented respiratory or anastomotic infections unless on appropriate antimicrobial therapy with evidence of clinical response
Women who are pregnant, wishing to become pregnant, or unwilling to use appropriate birth control to avoid becoming pregnant
Women who are breastfeeding
Clinically significant bronchial stenosis unresponsive to dilation and/or stenting
Malignancies diagnosed within one year prior to screening (with the exception of non-melanomatous skin cancers)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00755781

Locations

United States, California
UCLA School of Medicine
Los Angeles, California, United States, 90095
University of California, San Francisco
San Francisco, California, United States, 94143
Stanford University Medical Center
Stanford, California, United States, 94305
United States, Colorado
University of Colorado Health Sciences Center
Denver, Colorado, United States, 80262
United States, Florida
University of Florida Health Sciences Center
Gainesville, Florida, United States, 32610
Mayo Clinic
Jacksonville, Florida, United States, 32224
Tampa General Hospital
Tampa, Florida, United States, 33601
United States, Illinois
University of Chicago Hospitals
Chicago, Illinois, United States, 60637
Loyola University Hospital
Maywood, Illinois, United States, 60153
United States, Indiana
Indiana Methodist Research Institute
Indianapolis, Indiana, United States, 46202
United States, Maryland
University of Maryland
Baltimore, Maryland, United States, 21201
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
New York Presbyterian Hospital, Columbia University Med. Ctr.
New York, New York, United States, 10032
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Virginia
Inova Fairfax Hospital
Falls Church, Virginia, United States, 22402
Canada, Ontario
University of Toronto
Toronto, Ontario, Canada, M5G 2N2

Sponsors and Collaborators

APT Pharmaceuticals, Inc.

Investigators

Study Director:

Stephen Dilly, MD PhD

APT Pharmaceuticals, Inc.

More Information

Publications:

Burkart GJ, Smaldone GC, Eldon MA, Venkataramanan R, Dauber J, Zeevi A, McCurry K, McKaveney TP, Corcoran TE, Griffith BP, Iacono AT. Lung deposition and pharmacokinetics of cyclosporine after aerosolization in lung transplant patients. Pharm Res. 2003 Feb;20(2):252-6.

Iacono AT, Smaldone GC, Keenan RJ, Diot P, Dauber JH, Zeevi A, Burckart GJ, Griffith BP. Dose-related reversal of acute lung rejection by aerosolized cyclosporine. Am J Respir Crit Care Med. 1997 May;155(5):1690-8.

Keenan RJ, Iacono A, Dauber JH, Zeevi A, Yousem SA, Ohori NP, Burckart GJ, Kawai A, Smaldone GC, Griffith BP. Treatment of refractory acute allograft rejection with aerosolized cyclosporine in lung transplant recipients. J Thorac Cardiovasc Surg. 1997 Feb;113(2):335-40; discussion 340-1.

Iacono A, Dauber J, Keenan R, Spichty K, Cai J, Grgurich W, Burckart G, Smaldone G, Pham S, Ohori NP, Yousem S, Williams P, Griffith B, Zeevi A. Interleukin 6 and interferon-gamma gene expression in lung transplant recipients with refractory acute cellular rejection: implications for monitoring and inhibition by treatment with aerosolized cyclosporine. Transplantation. 1997 Jul 27;64(2):263-9.

Iacono AT, Johnson BA, Grgurich WF, Youssef JG, Corcoran TE, Seiler DA, Dauber JH, Smaldone GC, Zeevi A, Yousem SA, Fung JJ, Burckart GJ, McCurry KR, Griffith BP. A randomized trial of inhaled cyclosporine in lung-transplant recipients. N Engl J Med. 2006 Jan 12;354(2):141-50.

Iacono AT, Corcoran TE, Griffith BP, Grgurich WF, Smith DA, Zeevi A, Smaldone GC, McCurry KR, Johnson BA, Dauber JH. Aerosol cyclosporin therapy in lung transplant recipients with bronchiolitis obliterans. Eur Respir J. 2004 Mar;23(3):384-90.

Iacono AT, Keenan RJ, Duncan SR, Smaldone GC, Dauber JH, Paradis IL, Ohori NP, Grgurich WF, Burckart GJ, Zeevi A, Delgado E, O'Riordan TG, Zendarsky MM, Yousem SA, Griffith BP. Aerosolized cyclosporine in lung recipients with refractory chronic rejection. Am J Respir Crit Care Med. 1996 Apr;153(4 Pt 1):1451-5.

Responsible Party:	APT Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00755781 History of Changes
Other Study ID Numbers:	CIS001
Study First Received:	September 17, 2008
Last Updated:	September 13, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by APT Pharmaceuticals, Inc.:

lung transplant
lung transplant recipient
bronchiolitis obliterans syndrome
bronchiolitis obliterans

single lung transplant
double lung transplant
heart-lung transplant
Aerosol

Additional relevant MeSH terms:

Bronchiolitis
Bronchiolitis Obliterans
Bronchitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Infections
Cyclosporins
Cyclosporine
Enzyme Inhibitors

Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on June 18, 2013

Study of Cyclosporine Inhalation Solution (CIS) in Improving Bronchiolitis Obliterans Syndrome-Free Survival Following Lung Transplantation (CIS001)