Deposition of Inhaled Prolastin in Cystic Fibrosis Patients (CF2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Grifols Therapeutics Inc.
ClinicalTrials.gov Identifier:
NCT00486837
First received: June 13, 2007
Last updated: August 5, 2014
Last verified: August 2014
  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 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Grifols Therapeutics Inc.:

Primary Outcome Measures:
  • Change in Free Elastase in Induced Sputum From Baseline to Week 4 [ Time Frame: Baseline vs Week 4 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in Alpha-1-anti-trypsin (A1AT) Activity in Induced Sputum From Baseline at Week 4 [ Time Frame: Baseline vs Week 4 ] [ Designated as safety issue: No ]
  • Change in Total Immunoglobulin G (IgG) Fragments in Induced Sputum From Baseline at Week 4 [ Time Frame: Baseline vs Week 4 ] [ Designated as safety issue: No ]
  • Change in Total Bacterial Load in Induced Sputum From Baseline to Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
  • Change in Pseudomonas Load in Induced Sputum From Baseline at Week 4 [ Time Frame: Baseline vs Week 4 ] [ Designated as safety issue: No ]
  • Change in Neutrophil Number in Induced Sputum From Baseline at Week 4 [ Time Frame: Baseline vs Week 4 ] [ Designated as safety issue: No ]

Enrollment: 72
Study Start Date: December 2003
Study Completion Date: June 2004
Primary Completion Date: June 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Sponsors and Collaborators
Grifols Therapeutics Inc.
Investigators
Principal Investigator: Matthias Griese, MD Kinderklinik und Kinderpoliklinik im Haunerschen Kinderspital
  More Information

Additional Information:
Publications:
Responsible Party: Grifols Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT00486837     History of Changes
Other Study ID Numbers: 100452
Study First Received: June 13, 2007
Results First Received: September 24, 2009
Last Updated: August 5, 2014
Health Authority: Germany: Ethics Commission

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
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014