Aerosol Cyclosporine in Chronic Obstructive Pulmonary Disease (COPD)

NCT00783107 | Completed Phase 1 DMC

• 1 other identifier: 0611109
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blinded, Phase I dose escalation-deescalation protocol (DEP) of cyclosporine inhalation solution in patients with Gold Stage III chronic obstructive pulmonary disease. The purpose of the study is to evaluate the safety and effectiveness of aerosolized Cyclosporine in treating COPD. The specific aims of the study are:

1. 1.To identify the short term (28 day) safety profile of CyIS immunotherapy in severe COPD (GOLD III) patients with particular attention to airway reactivity and infection risk.
2. 2.To identify the pharmacokinetic-pharmacodynamic relationship of CyIS using peripheral blood markers of an adaptive immune response as endpoints in subjects with severe COPD (GOLD III) treated short-term.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Gold Stage III COPD

Outcome Measures

Primary Outcomes (1)

• To evaluate the safety and effectiveness of aerosol cyclosporine (CyIS) an immunomodulating therapeutic in treating COPD

  Short term (28 day) safety profile

Study Arms (2)

Cyclosporine

EXPERIMENTAL

Drug: Cyclosporine

Placebo

PLACEBO COMPARATOR

Subjects will be randomly assigned to Cyclosporine or placebo, in a ratio of 2:1.

Drug: Placebo

Interventions

Cyclosporine DRUG

Cyclosporine Inhalation Solution, Once Daily

Cyclosporine

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 45 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 45 and 70 years.
• A confirmed diagnosis of COPD, Gold Stage III, 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.
• Subjects agree to maintain a stable medication regimen in the absence of a disease flare
• ECOG performance status of 0, 1, or 2.
• pCO2 \< 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, and undergo monthly pregnancy testing.
• Elevated T-cell cytokine gene expression, defined as baseline values \> the mean of the pilot Gold 0-1 study population for one variable (CD4+IL-2 \>23%, CD8+IFN-g \>17%, CD8+MHC \> 6%, or CD8 TGF-b).
• 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), other than aerosolized corticosteroids, anytime within three months prior to participation
• Evidence for an opportunistic infection/colonization of the airways, i.e., non-bacterial
• Use of aerosolized corticosteroids with an inability to maintain inhaled corticosteroid therapy dosing without change during the study interval
• Evidence for systemic illness including hematologic disorders (defined by an absolute neutrophil count (ANC) \< 4000 /mL and platelets \< 120,000/mL), renal insufficiency (serum creatinine \> 2.0 mg/dL), cirrhosis, or hepatic insufficiency (total bilirubin, or alkaline phosphatase \> 1.5 x normal, SGOT, or SGPT \> 1.2 x normal values), or a coagulopathy (INR \> 1.4), seizure disorder.
• Evidence for systemic abnormal renal function manifested by uncontrolled hypertension (systolic blood pressure \> 160mmHg or diastolic blood pressure \>90mmHg), hyperkalemia (serum creatinine \> 5.0 meq/dl, and/or elevated serum creatinine above the normal range for the subject's age.
• Evidence of coronary artery disease by history, e.g., angina or history of myocardial infarction within the past 12 months, unless corrected by CABG within \< 5 years, and asymptomatic since
• Pregnant or breast feeding females or women of childbearing potential not practicing birth control during and for 6 months following treatment, or fertile and sexually active males unwilling to use contraceptive techniques 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 propylene glycol, CsA, or lidocaine
• Concurrent enrollment or participation within the prior month in other clinical trials

Sponsors & Collaborators

• University of Pittsburgh: lead

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

Study Officials

• Michael Donahoe, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

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

Study Record Dates

• First Submitted: October 30, 2008
• First Posted: October 31, 2008
• Study Start: October 1, 2007
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: December 11, 2012

Record last verified: 2012-12

Locations

US (1)