Deposition of Inhaled Prolastin in Cystic Fibrosis Patients (CF2)

Grifols

Status and phase

Completed

Phase 2

Conditions

Cystic Fibrosis

Treatments

Drug: Alpha1-Proteinase Inhibitor (Human)

Study type

Interventional

Funder types

Industry

Identifiers

NCT00486837

100452

Details and patient eligibility

About

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.

Full 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.

Enrollment

72 patients

Sex

All

Ages

8+ years old

Volunteers

No Healthy Volunteers

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