Deposition of Inhaled Prolastin in Cystic Fibrosis Patients - Full Text View

Sponsor:	Talecris Biotherapeutics
Information provided by:	Talecris Biotherapeutics
ClinicalTrials.gov Identifier:	NCT00486837

Purpose

The objective of this trial is to determine the optimal region of the lung for depositing Prolastin (alpha-1 antitrypsin; AAT) by inhalation in order to treat cystic fibrosis (CF). The AKITA® nebulizer has settings which can be varied to target the inhaled drug to either the deep lung or to the upper airways in a one to one randomization. The study will measure how much of the activity of the enzyme elastase is inhibited by AAT.

Condition	Intervention	Phase
Cystic Fibrosis	Drug: Alpha1-Proteinase Inhibitor (Human)	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Dose Comparison, Parallel Assignment, Efficacy Study
Official Title:	Multicenter, Randomized, Parallel Group Study to Investigate the Optimal Deposition Site for Inhaled Prolastin® in Patients With Cystic Fibrosis (CF)

Resource links provided by NLM:

Genetics Home Reference related topics: cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis

U.S. FDA Resources

Further study details as provided by Talecris Biotherapeutics:

Primary Outcome Measures:

change in free elastase in induced sputum [ Time Frame: baseline vs week 4 ]

Secondary Outcome Measures:

Standard lung function parameters (FEV1, FVC, FEV1/FVC, MEF) [ Time Frame: baseline vs week 4 ]
AAT activity in induced sputum [ Time Frame: baseline vs week 4 ]
total IgG fragments in induced sputum [ Time Frame: baseline vs week 4 ]
total bacterial load in induced sputum [ Time Frame: baseline vs week 4 ]
Pseudomonas load in induced sputum [ Time Frame: baseline vs week 4 ]
Neutrophil number in induced sputum [ Time Frame: baseline vs week 4 ]

Enrollment:	72
Study Start Date:	December 2003
Study Completion Date:	June 2004

Arms	Assigned Interventions
Group 1: Experimental Bronchial Deposition	Drug: Alpha1-Proteinase Inhibitor (Human)
Group 2: Experimental Peripheral Deposition	Drug: Alpha1-Proteinase Inhibitor (Human)

Detailed Description:

The optimum deposition site (bronchial or peripheral) in CF patients for AAT will be investigated by measuring several parameters in induced sputum. The study will start with a 2 week run-in period in which the planned 60 patients inhale isotonic saline once daily. This period is followed by a 4 week treatment period where 30 patients inhale AAT for peripheral deposition and 30 patients inhale AAT for bronchial deposition. Six patients in each group will be asked to collect spontaneous sputum at home.

Twenty-five milligrams of AAT will be deposited at one of the two target sites using the AKITA® device. The inhalation should take place in the evening between 18.00 and 23.00 h.

Patients will inhale saline once daily for 2 weeks (run-in period) followed by 4 weeks of once daily inhalation of AAT. Induced sputum will be collected at visits to the clinic at the start of the run-in, at the start of AAT treatment, and at 2 and 4 weeks after the start of AAT treatment.

Eligibility

Ages Eligible for Study:	8 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patient with diagnosis of CF
Age >= 8 years
FEV1 > 25 % of predicted value
Free elastase activity checked at visit 1 must be positive (free elastolytic activity in the sample, 2 standard deviations above of the negative blank samples in the assay.) .
Patient must be positive at least 3 times for pseudomonas in the last 2 years
Patient must be positive for pseudomonas at Visit 1
Patient must be able to perform reliable spirometry
Patient must be on stable concomitant therapy at least 2 weeks prior to visit 1 and during the study
Written informed consent of the patient or legal representative(s)

Exclusion Criteria:

FEV1 < 25% of predicted value post-bronchodilator
History of lung transplant
Any lung surgery within the past 2 years
On any thoracic surgery waiting list
Severe concomitant disease (serious malignant disease, congestive heart failure NYHA III/IV, cor pulmonale with the need of oxygen therapy)
Severe liver cirrhosis with ascites, hypersplenism or grade III/IV esophageal varices.
Known selective IgA deficiency with known antibody against IgA (anti-IgA antibody)
Active pulmonary exacerbation within the 4 weeks prior to screening
Current Smoking
Pregnancy or lactation
Women of child-bearing age without adequate contraception
Any medical condition which the investigator feels will prohibit the patient from completing the trial
Participation in another clinical trial within 30 days prior to inclusion at visit 1

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00486837

Sponsors and Collaborators

Talecris Biotherapeutics

Investigators

Principal Investigator:

Matthias Griese, MD

Kinderklinik und Kinderpoliklinik im Haunerschen Kinderspital

More Information

Additional Information:

FDA Approved Product Labeling Information This link exits the ClinicalTrials.gov site

FDA Enforcement Report Index (Class I, Class II Recall, Market Alerts and Medical Product Safety Alerts) This link exits the ClinicalTrials.gov site

CF2 Synopsis of Study Results This link exits the ClinicalTrials.gov site

Publications:

Griese M, Latzin P, Kappler M, Weckerle K, Heinzlmaier T, Bernhardt T, Hartl D. alpha1-Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients. Eur Respir J. 2007 Feb;29(2):240-50. Epub 2006 Oct 18.

Study ID Numbers:	100452
Study First Received:	June 13, 2007
Last Updated:	May 7, 2008
ClinicalTrials.gov Identifier:	NCT00486837 History of Changes
Health Authority:	Germany: Ethics Commission

Additional relevant MeSH terms:

Serine Proteinase Inhibitors
Molecular Mechanisms of Pharmacological Action
Fibrosis
Enzyme Inhibitors
Pharmacologic Actions
Protease Inhibitors
Alpha 1-Antitrypsin
Digestive System Diseases

Pathologic Processes
Cystic Fibrosis
Respiratory Tract Diseases
Genetic Diseases, Inborn
Lung Diseases
Trypsin Inhibitors
Pancreatic Diseases
Infant, Newborn, Diseases

ClinicalTrials.gov processed this record on November 09, 2009