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

NCT00755781 | Completed Phase 3 DMC

• 1 other identifier: CIS001
• Study Type: interventional
• Target: 284
• Locations: 2 countries
• Sites: 19

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.

Conditions

Lung Transplant

Keywords

lung transplant; lung transplant recipient; bronchiolitis obliterans syndrome; bronchiolitis obliterans; single lung transplant; double lung transplant; heart-lung transplant; Aerosol

Outcome Measures

Primary Outcomes (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

  Assessed when symptoms of syndrome present

Secondary Outcomes (3)

• Pulmonary function as measured by mean FEV1 percent predicted at 2 years after randomization

  From study initiation through 2+ years after randomization

• All cause mortality

  From study initiation through 2+ years after randomization

• 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

Study Arms (2)

CIS

ACTIVE COMPARATOR

CIS in addition to standard immunosuppressive regimen.

Drug: Cyclosporine Inhalation Solution (CIS)

SOC

NO INTERVENTION

Standard of care (SOC) therapy for lung transplant recipients

Interventions

Cyclosporine Inhalation Solution (CIS) DRUG

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)

Also known as: Cyclosporine

CIS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• APT Pharmaceuticals, Inc.: lead

Study Sites (19)

UCLA School of Medicine

Los Angeles, California, 90095, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

University of Colorado Health Sciences Center

Denver, Colorado, 80262, United States

Location

University of Florida Health Sciences Center

Gainesville, Florida, 32610, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Tampa General Hospital

Tampa, Florida, 33601, United States

Location

University of Chicago Hospitals

Chicago, Illinois, 60637, United States

Location

Loyola University Hospital

Maywood, Illinois, 60153, United States

Location

Indiana Methodist Research Institute

Indianapolis, Indiana, 46202, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

New York Presbyterian Hospital, Columbia University Med. Ctr.

New York, New York, 10032, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22402, United States

Location

University of Toronto

Toronto, Ontario, M5G 2N2, Canada

Location

Related Publications (8)

• 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. doi: 10.1023/a:1022275222207.

  PMID: 12636164 BACKGROUND

• 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. doi: 10.1164/ajrccm.155.5.9154878.

  PMID: 9154878 BACKGROUND

• 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. doi: 10.1016/S0022-5223(97)70331-3.

  PMID: 9040628 BACKGROUND

• 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. doi: 10.1097/00007890-199707270-00015.

  PMID: 9256185 BACKGROUND

• 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. doi: 10.1056/NEJMoa043204.

  PMID: 16407509 BACKGROUND

• 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. doi: 10.1183/09031936.04.00058504.

  PMID: 15065826 BACKGROUND

• 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. doi: 10.1164/ajrccm.153.4.8616581.

  PMID: 8616581 BACKGROUND

• 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.

  PMID: 23668548 DERIVED

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome; Bronchiolitis Obliterans

Interventions

Cyclosporine

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Stephen Dilly, MD PhD

  APT Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2008
• First Posted: September 19, 2008
• Study Start: September 1, 2008
• Primary Completion: September 1, 2011
• Study Completion: November 1, 2011
• Last Updated: September 17, 2012

Record last verified: 2012-09

Locations

CA (1); US (18)