Deposition of Inhaled Prolastin in Cystic Fibrosis Patients

NCT00486837 | Completed Phase 2 Results

• 1 other identifier: 100452
• Study Type: interventional
• Target: 72
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• Change in Free Elastase in Induced Sputum From Baseline to Week 4

  Baseline vs Week 4

Secondary Outcomes (5)

• Change in Alpha-1-anti-trypsin (A1AT) Activity in Induced Sputum From Baseline at Week 4

  Baseline vs Week 4

• Change in Total Immunoglobulin G (IgG) Fragments in Induced Sputum From Baseline at Week 4

  Baseline vs Week 4

• Change in Total Bacterial Load in Induced Sputum From Baseline to Week 4

  Week 4

• Change in Pseudomonas Load in Induced Sputum From Baseline at Week 4

  Baseline vs Week 4

• Change in Neutrophil Number in Induced Sputum From Baseline at Week 4

  Baseline vs Week 4

Study Arms (2)

Group 1

EXPERIMENTAL

Bronchial Deposition Intervention: Alpha1-Proteinase Inhibitor (Human) Dosage: 25 mg in lungs, one inhalation per day over 4 weeks

Drug: Alpha1-Proteinase Inhibitor (Human)

Group 2

EXPERIMENTAL

Peripheral Deposition Intervention: Alpha1-Proteinase Inhibitor (Human) Dosage: 25 mg in lungs, one inhalation per day over 4 weeks

Drug: Alpha1-Proteinase Inhibitor (Human)

Interventions

Alpha1-Proteinase Inhibitor (Human) DRUG

25 mg of Alpha1-Proteinase Inhibitor (Human) in the lungs, one inhalation per day over 4 weeks.

Also known as: Prolastin®, Alpha-1 antitrypsin (AAT), BAY x 5747, BAY 10-5233, TAL-05-00007, A1AT, NDC 13533-601-30, NDC 13533-601-35

Group 1; Group 2

Eligibility Criteria

• Age: 8 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Grifols Therapeutics LLC: lead

Related Publications (1)

• 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. doi: 10.1183/09031936.00047306. Epub 2006 Oct 18.

  PMID: 17050563 RESULT

Related Links

• FDA Approved Product Labeling Information

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

alpha 1-Antitrypsin

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Acute-Phase Proteins; Blood Proteins; Proteins; Alpha-Globulins; Serum Globulins; Globulins

Results Point of Contact

• Title: Henry Li
• Organization: Grifols Therapeutics

henry.li@grifols.com

1-800-520-2807

Study Officials

• Matthias Griese, MD

  Kinderklinik und Kinderpoliklinik im Haunerschen Kinderspital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2007
• First Posted: June 15, 2007
• Study Start: December 1, 2003
• Primary Completion: June 1, 2004
• Study Completion: June 1, 2004
• Last Updated: August 21, 2014
• Results First Posted: August 21, 2014

Record last verified: 2014-08