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

• ClinicalTrials.gov Identifier: NCT00755781
• Recruitment Status: Completed
• First Posted: September 19, 2008
• Last Update Posted: September 17, 2012
• Sponsor: APT Pharmaceuticals, Inc.
• Information provided by (Responsible Party): APT Pharmaceuticals, Inc.

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Lung Transplant	Drug: Cyclosporine Inhalation Solution (CIS)	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 284 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Study Start Date: September 2008
• Actual Primary Completion Date: September 2011
• Actual Study Completion Date: November 2011

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. 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 ]

Secondary Outcome Measures :

1. Pulmonary function as measured by mean FEV1 percent predicted at 2 years after randomization [ Time Frame: From study initiation through 2+ years after randomization ]
2. All cause mortality [ Time Frame: From study initiation through 2+ years after randomization ]
3. 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 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Corcoran TE, Niven R, Verret W, Dilly S, Johnson BA. Lung deposition and pharmacokinetics of nebulized cyclosporine in lung transplant patients. J Aerosol Med Pulm Drug Deliv. 2014 Jun;27(3):178-84. doi: 10.1089/jamp.2013.1042. Epub 2013 May 13.

• Responsible Party: APT Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT00755781
• Other Study ID Numbers: CIS001
• First Posted: September 19, 2008
• Last Update Posted: September 17, 2012
• Last Verified: September 2012

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:

Lung Diseases, Obstructive; Lung Diseases; Cyclosporine; Cyclosporins; Bronchiolitis; Bronchiolitis Obliterans; Respiratory Tract Diseases; Bronchitis; Respiratory Tract Infections; Infections; Bronchial Diseases; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antifungal Agents; Anti-Infective Agents; Dermatologic Agents; Antirheumatic Agents; Calcineurin Inhibitors