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

Primary Purpose

Lung Transplant

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Cyclosporine Inhalation Solution (CIS)
Sponsored by
APT Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Lung Transplant focused on measuring lung transplant, lung transplant recipient, bronchiolitis obliterans syndrome, bronchiolitis obliterans, single lung transplant, double lung transplant, heart-lung transplant, Aerosol

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • UCLA School of Medicine
  • University of California, San Francisco
  • Stanford University Medical Center
  • University of Colorado Health Sciences Center
  • University of Florida Health Sciences Center
  • Mayo Clinic
  • Tampa General Hospital
  • University of Chicago Hospitals
  • Loyola University Hospital
  • Indiana Methodist Research Institute
  • University of Maryland
  • University of Minnesota
  • New York Presbyterian Hospital, Columbia University Med. Ctr.
  • Cleveland Clinic
  • Hospital of the University of Pennsylvania
  • University of Pittsburgh Medical Center
  • Baylor College of Medicine
  • Inova Fairfax Hospital
  • University of Toronto

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

CIS

SOC

Arm Description

CIS in addition to standard immunosuppressive regimen.

Standard of care (SOC) therapy for lung transplant recipients

Outcomes

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

Secondary Outcome Measures

Pulmonary function as measured by mean FEV1 percent predicted at 2 years after randomization
All cause mortality
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)

Full Information

First Posted
September 17, 2008
Last Updated
September 13, 2012
Sponsor
APT Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00755781
Brief Title
Study of Cyclosporine Inhalation Solution (CIS) in Improving Bronchiolitis Obliterans Syndrome-Free Survival Following Lung Transplantation
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2012
Overall Recruitment Status
Completed
Study Start Date
September 2008 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
November 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
APT Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Transplant
Keywords
lung transplant, lung transplant recipient, bronchiolitis obliterans syndrome, bronchiolitis obliterans, single lung transplant, double lung transplant, heart-lung transplant, Aerosol

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
284 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CIS
Arm Type
Active Comparator
Arm Description
CIS in addition to standard immunosuppressive regimen.
Arm Title
SOC
Arm Type
No Intervention
Arm Description
Standard of care (SOC) therapy for lung transplant recipients
Intervention Type
Drug
Intervention Name(s)
Cyclosporine Inhalation Solution (CIS)
Other Intervention Name(s)
Cyclosporine
Intervention Description
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)
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
Pulmonary function as measured by mean FEV1 percent predicted at 2 years after randomization
Time Frame
From study initiation through 2+ years after randomization
Title
All cause mortality
Time Frame
From study initiation through 2+ years after randomization
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen Dilly, MD PhD
Organizational Affiliation
APT Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
UCLA School of Medicine
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Stanford University Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University of Colorado Health Sciences Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80262
Country
United States
Facility Name
University of Florida Health Sciences Center
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Mayo Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Tampa General Hospital
City
Tampa
State/Province
Florida
ZIP/Postal Code
33601
Country
United States
Facility Name
University of Chicago Hospitals
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Loyola University Hospital
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Indiana Methodist Research Institute
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
New York Presbyterian Hospital, Columbia University Med. Ctr.
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Inova Fairfax Hospital
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22402
Country
United States
Facility Name
University of Toronto
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2N2
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
12636164
Citation
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.
Results Reference
background
PubMed Identifier
9154878
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. doi: 10.1164/ajrccm.155.5.9154878.
Results Reference
background
PubMed Identifier
9040628
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. doi: 10.1016/S0022-5223(97)70331-3.
Results Reference
background
PubMed Identifier
9256185
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. doi: 10.1097/00007890-199707270-00015.
Results Reference
background
PubMed Identifier
16407509
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. doi: 10.1056/NEJMoa043204.
Results Reference
background
PubMed Identifier
15065826
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. doi: 10.1183/09031936.04.00058504.
Results Reference
background
PubMed Identifier
8616581
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. doi: 10.1164/ajrccm.153.4.8616581.
Results Reference
background
PubMed Identifier
23668548
Citation
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.
Results Reference
derived

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

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