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Deposition of Inhaled Prolastin in Cystic Fibrosis Patients (CF2)

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ClinicalTrials.gov Identifier: NCT00486837
Recruitment Status : Completed
First Posted : June 15, 2007
Results First Posted : August 21, 2014
Last Update Posted : August 21, 2014
Sponsor:
Information provided by (Responsible Party):
Grifols Therapeutics LLC

Brief Summary:
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 or disease Intervention/treatment Phase
Cystic Fibrosis Drug: Alpha1-Proteinase Inhibitor (Human) Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter, Randomized, Parallel Group Study to Investigate the Optimal Deposition Site for Inhaled Prolastin® in Patients With Cystic Fibrosis (CF)
Study Start Date : December 2003
Actual Primary Completion Date : June 2004
Actual Study Completion Date : June 2004


Arm Intervention/treatment
Experimental: Group 1
Bronchial Deposition Intervention: Alpha1-Proteinase Inhibitor (Human) Dosage: 25 mg in lungs, one inhalation per day over 4 weeks
Drug: Alpha1-Proteinase Inhibitor (Human)
25 mg of Alpha1-Proteinase Inhibitor (Human) in the lungs, one inhalation per day over 4 weeks.
Other Names:
  • Prolastin®
  • Alpha-1 antitrypsin (AAT)
  • BAY x 5747
  • BAY 10-5233
  • TAL-05-00007
  • A1AT
  • NDC 13533-601-30
  • NDC 13533-601-35
Experimental: Group 2
Peripheral Deposition Intervention: Alpha1-Proteinase Inhibitor (Human) Dosage: 25 mg in lungs, one inhalation per day over 4 weeks
Drug: Alpha1-Proteinase Inhibitor (Human)
25 mg of Alpha1-Proteinase Inhibitor (Human) in the lungs, one inhalation per day over 4 weeks.
Other Names:
  • Prolastin®
  • Alpha-1 antitrypsin (AAT)
  • BAY x 5747
  • BAY 10-5233
  • TAL-05-00007
  • A1AT
  • NDC 13533-601-30
  • NDC 13533-601-35



Primary Outcome Measures :
  1. Change in Free Elastase in Induced Sputum From Baseline to Week 4 [ Time Frame: Baseline vs Week 4 ]

Secondary Outcome Measures :
  1. Change in Alpha-1-anti-trypsin (A1AT) Activity in Induced Sputum From Baseline at Week 4 [ Time Frame: Baseline vs Week 4 ]
  2. Change in Total Immunoglobulin G (IgG) Fragments in Induced Sputum From Baseline at Week 4 [ Time Frame: Baseline vs Week 4 ]
  3. Change in Total Bacterial Load in Induced Sputum From Baseline to Week 4 [ Time Frame: Week 4 ]
  4. Change in Pseudomonas Load in Induced Sputum From Baseline at Week 4 [ Time Frame: Baseline vs Week 4 ]
  5. Change in Neutrophil Number in Induced Sputum From Baseline at Week 4 [ Time Frame: Baseline vs Week 4 ]


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Ages Eligible for Study:   8 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient with diagnosis of CF
  • Age >= 8 years
  • Forced expiratory volume at one second (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 New York Heart Association (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 immunoglobulin A (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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00486837


Sponsors and Collaborators
Grifols Therapeutics LLC
Investigators
Principal Investigator: Matthias Griese, MD Kinderklinik und Kinderpoliklinik im Haunerschen Kinderspital

Additional Information:
Publications of Results:
Responsible Party: Grifols Therapeutics LLC
ClinicalTrials.gov Identifier: NCT00486837     History of Changes
Other Study ID Numbers: 100452
First Posted: June 15, 2007    Key Record Dates
Results First Posted: August 21, 2014
Last Update Posted: August 21, 2014
Last Verified: August 2014

Additional relevant MeSH terms:
Fibrosis
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Alpha 1-Antitrypsin
Protease Inhibitors
Trypsin Inhibitors
Serine Proteinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action