CIS001 Extension Study of Cyclosporine Inhalation Solution (CIS002)

CIS002: An Open-Label, Multi-Center, Extension Study of Cyclosporine Inhalation Solution in Subjects Previously Enrolled in the APT Study CIS001

This trial is a longterm follow up of a phase III study of inhaled cyclosporine for the prevention of chronic rejection in lung transplant recipients.

Study Overview

• Status: Terminated
• Conditions: Lung Transplant
• Intervention / Treatment: Drug: Cyclosporine Inhalation Solution (CIS)

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Enrollment in study CIS001
2. Written informed consent for CIS002
3. Use of an effective means of contraception by women of childbearing potential

Exclusion Criteria:

1. Any unresolved or irreversible CIS-related ongoing serious adverse event
2. Subjects who have developed newly emergent conditions, injuries, diagnoses, physical examination findings, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk of treatment complications
3. Subjects with suspected or documented allergy to propylene glycol and/or cyclosporine
4. Women who are pregnant, wishing to become pregnant, or unwilling to use appropriate birth control to avoid becoming pregnant
5. Women who are breastfeeding
6. Subjects unable to comply with all protocol requirements and follow-up procedures
7. Subjects who discontinued from CIS002 to participate in another clinical trial and have received any investigational treatment (other than CIS) within 14 days of titration visit 1/baseline.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Inhaled cyclosporine; Extended access to inhaled cyclosporine for patients from treatment and control arms of Phase 3 study CIS001	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To assess the long-term safety of CIS administration	5 years

Collaborators and Investigators

• Sponsor: APT Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Bruce A Johnson, MD, University of Pittsburgh; Principal Investigator: Jeffrey Golden, MD, University of California, San Francisco

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: July 9, 2009
• First Submitted That Met QC Criteria: July 10, 2009
• First Posted (Estimate): July 13, 2009

Study Record Updates

• Last Update Posted (Estimate): September 17, 2012
• Last Update Submitted That Met QC Criteria: September 13, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: bronchiolitis obliterans; Aerosol; lung transplant; bronchiolitis obliterans syndrome; lung transplant recipient; single lung transplant; double lung transplant; heart-lung transplant
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Respiratory Aspiration; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: CIS002