Oral Cyclosporine in Chronic Obstructive Pulmonary Disease

NCT00974142 | Completed Phase 1 Results DMC

• 1 other identifier: PRO09050330
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blinded, placebo-controlled trial of oral Cyclosporine A (CsA) in patients with advanced stage chronic obstructive pulmonary disease. The purpose of the study is to evaluate the safety and effectiveness of CsA as a therapy for the adaptive immune response in advanced stage Chronic Obstructive Pulmonary Disease (COPD). Subjects between 45 and 80 years of age with a confirmed diagnosis of advanced stage COPD, not responsive to conventional inhaler therapy, who meet all the study requirements, will be enrolled in this study. A total of 30 subjects of either sex will be enrolled in this study.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD; Chronic Obstructive Pulmonary Disease; Cyclosporine; Oral Immunotherapy; Advanced stage

Outcome Measures

Primary Outcomes (3)

• Safety Profile of Oral Cyclosporin A Immunotherapy in Advanced Stage Chronic Obstructive Pulmonary Disease Patients- Nephrotoxicity - Measured by Serum Creatinine

  Measurement of nephrotoxicity by monitoring serum creatinine over 16 week treatment interval. Mean serum creatinine values were assessed at Week 2, 4, 6, 8, 10, 12 and 16. The mean values of all measurements for each participant were calculated and then the mean across participants was calculated. Values expressed as mean ± SD.

  16 weeks

• Safety Profile of Oral Cyclosporin A Immunotherapy in Advanced Stage Chronic Obstructive Pulmonary Disease Patients - Number of Patients That Developed Renal Insufficiency

  Development of renal insufficiency defined as \> 30% elevation in serum creatinine above baseline which required dose modification of the cyclosporine over 16 week treatment interval at Week 2, 4, 6, 8, 10, 12 and 16. Outcome measured the number of subjects who developed renal insufficiency during the study treatment interval.

  16 weeks

• Safety Profile of Oral Cyclosporin A Immunotherapy in Advanced Stage Chronic Obstructive Pulmonary Disease Patients - Number of Patients That Developed Infection Requiring Systemic Antibiotic Therapy

  Clinical diagnosis of infection which requires systemic antibiotic therapy during the 16 week study interval at Week 2, 4, 6, 8, 10, 12 and 16. Outcome measured the number of subjects who developed an infection requiring systemic antibiotic therapy during the study treatment interval.

  16 weeks

Secondary Outcomes (11)

• Pharmacokinetic - Pharmacodynamic Relationship of Oral Cyclosporine and Biomarkers of an Adaptive Immune Response - Cyclosporine Blood Levels

  16 weeks

• Peripheral Blood T Cell Biomarkers Over 16 Week Treatment Interval - Change in the Percentage of Cluster of Differentiation 4 (CD4)

  at Week 8 and Week 16

• Peripheral Blood T Cell Biomarkers Over 16 Week Treatment Interval - Change in the Percentage of Cluster of Differentiation 8 and Cluster of Differentiation 28

  at Week 8 and Week 16

• Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 8 and Major Histocompatibility Complex II

  at Week 8 and Week 16

• Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 8+ Interferon Gamma

  at Week 8 and Week 16

Study Arms (2)

Cyclosporine

EXPERIMENTAL

Drug: Cyclosporine

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Cyclosporine DRUG

Fifteen patients will receive cyclosporine at an initial dosing of 3.0 mg/kg/day.

Also known as: Neoral

Cyclosporine

Placebo DRUG

Fifteen patients will receive will receive placebo.

Placebo

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 45 and 80 years
• A confirmed diagnosis of advanced stage COPD, using current accepted diagnostic criteria, including clinical/laboratory findings, pulmonary function tests, and appropriate history to exclude other disorders that could explain their lung disease. The accepted range of forced expiratory volume at one second will include 25% ≤ forced expiratory volume at one second ≤ 60%
• Subjects agree to maintain a stable medication regimen in the absence of a disease flare
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• carbon dioxide partial pressure \< 45 mm Hg, room air oxyhemoglobin saturation \> 85%
• A willingness to participate in all portions of the protocol, including serial bronchoscopy, requisite surveillances, and ancillary immunologic studies in follow-up visits at this institution
• For woman of childbearing age, a negative pregnancy test, and a willingness to use two methods of contraception, or abstinence
• An ability and willingness to provide written informed consent

You may not qualify if:

• Three, or more exacerbations of lower respiratory disease in the past year requiring systemic corticosteroids, or one exacerbation requiring hospitalization in the past 6 months
• Intubation for COPD, or other cause of respiratory failure in the past year
• Use of immunosuppressive therapy including oral prednisone \> 10mg per day other than aerosolized corticosteroids, anytime within three months prior to participation
• Evidence for an opportunistic infection/colonization of the airways, i.e., non-bacterial
• Evidence for systemic illness including hematologic disorders (defined by an absolute neutrophil count (ANC) \< 4000 /mL and platelets \< 120,000/mL), cirrhosis, or hepatic insufficiency (total bilirubin, or alkaline phosphatase \> 1.5 x normal, serum glutamate oxaloacetate transaminase, or serum glutamate pyruvate transaminase \> 1.2 x normal values), or a coagulopathy (INR \> 1.4), seizure disorder
• Evidence for renal insufficiency with a calculated creatinine clearance using the Cockcroft and Gault's method of \< 80 ml/min for males and \< 70 ml/min for females, or serum creatinine \> 1.4 mg/dL.
• Evidence of coronary artery disease by history, e.g., angina or history of myocardial infarction within the past 12 months, unless corrected by coronary artery bypass graft within \< 5 years, and asymptomatic since
• Evidence for systemic abnormal renal function manifested by uncontrolled hypertension (systolic blood pressure \> 160 mmHg or diastolic blood pressure \>90 mmHg), hyperkalemia (serum potassium \> 5.0 meq/dl, and/or elevated serum potassium above the normal range for the subject's age)
• Pregnancy or lactation, or inability to take contraception during and for 6 months following treatment
• Positive HIV, or hepatitis B or C serology, or another active infection
• Current or past history of cancer excluding basal or squamous cell skin cancer
• Undiagnosed pulmonary nodule requiring diagnostic evaluation
• Weight loss \> 10% usual body weight over the past 6 months or a BMI \< 18
• Known hypersensitivity or allergy to cyclosporine
• Concurrent participation in other clinical trials within the prior month

Sponsors & Collaborators

• Michael Donahoe: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Cyclosporine

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Michael Donahoe MD
• Organization: University of Pittsburgh Medical Center

donahoem@upmc.edu

412-648-9636

Study Officials

• Michael Donahoe, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 9, 2009
• First Posted: September 10, 2009
• Study Start: September 1, 2009
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: June 25, 2025
• Results First Posted: May 9, 2018

Record last verified: 2018-04

Locations

US (1)