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

Lung Transplant Clinical Trial

— CIS001  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00755781
• Other study ID #: CIS001
• Status: Completed
• Phase: Phase 3
• First received: September 17, 2008
• Last updated: September 13, 2012
• Start date: September 2008
• Est. completion date: November 2011

Study information

• Verified date: September 2012
• Source: APT Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 284
• Est. completion date: November 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Bronchiolitis
• Bronchiolitis Obliterans
• Lung Transplant

Intervention

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)

Locations

Country	Name	City	State
Canada	University of Toronto	Toronto	Ontario
United States	University of Maryland	Baltimore	Maryland
United States	University of Chicago Hospitals	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	University of Colorado Health Sciences Center	Denver	Colorado
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	University of Florida Health Sciences Center	Gainesville	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana Methodist Research Institute	Indianapolis	Indiana
United States	Mayo Clinic	Jacksonville	Florida
United States	UCLA School of Medicine	Los Angeles	California
United States	Loyola University Hospital	Maywood	Illinois
United States	University of Minnesota	Minneapolis	Minnesota
United States	New York Presbyterian Hospital, Columbia University Med. Ctr.	New York	New York
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	University of California, San Francisco	San Francisco	California
United States	Stanford University Medical Center	Stanford	California
United States	Tampa General Hospital	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
APT Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (7)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		Assessed when symptoms of syndrome present	No
Secondary	Pulmonary function as measured by mean FEV1 percent predicted at 2 years after randomization		From study initiation through 2+ years after randomization	No
Secondary	All cause mortality		From study initiation through 2+ years after randomization	No
Secondary	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)		From study initiation through 2+ year after randomzation	No