Double-Blind, Randomized, Placebo-Controlled, Phase II Study of the Safety and Efficacy of Inhaled Alpha-1 Antitrypsin (AAT ) in Cystic Fibrosis Patients
Overview
- Phase
- Phase 2
- Intervention
- Aerosolized, human, plasma-derived Alpha-1 Antitrypsin
- Conditions
- Cystic Fibrosis
- Sponsor
- Kamada, Ltd.
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- Safety and airway inflammation
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
Cystic Fibrosis (CF) is an inherited disorder in which mucus-secreting glands in the lungs produce considerable quantity of thick, sticky secretions that clog the airways, promote bacterial growth and lead to chronic obstruction, inflammation and destruction of the airways.
The purpose of this study is to collect data about the resolution of the chronic inflammatory state in addition to assure the safety of the therapy in CF patients.
Detailed Description
In CF patients the unregulated inflammatory response overwhelms the normal protease (elastase)/antiprotease (AAT) balance, leading to the accumulation of elastase in the lung, destruction of the lung architecture, severe pulmonary dysfunction, and ultimately death. Administration of AAT is to address the elastase/antiprotease imbalance in order to prevent destruction of the lung tissue and reduce the inflammatory dysregulation that causes pulmonary dysfunction.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of CF by clinical symptoms and positive sweat test or disease inducing mutation.
- •Age \>5 yrs
- •Proven ability to perform reproducible PFTs
- •FEV1 \>25% predicted
- •Steady disease state for 3 months and no decrease in lung function exceeding 10% during that period
- •Colonization
- •Stable concomitant therapy \>2 weeks prior to visit 1 and during the study
- •Non-tobacco user of any kind
- •Ability for sputum induction
- •Written informed consent
Exclusion Criteria
- •Severe CF with an FEV1 of \<25% predicted
- •History of lung transplant
- •Active allergic bronchopulmonary aspergillosis (ABPA)
- •Treatment with additional antibiotics (beyond standard CF treatment) for a period of 14 days before study entry (routine antibiotics permitted)
- •Treatment with additional oral and/or IV steroids (beyond standard CF treatment) for a period of 14 days before study entry (screening day)
- •Known hypersensitivity to plasma products
- •IgA deficiency
- •Uncontrolled hypertension
- •Lung surgery in the previous two years
- •Being on any thoracic surgery waiting list
Arms & Interventions
80 mg/kg AAT inhaled
80 mg/kg AAT inhaled
Intervention: Aerosolized, human, plasma-derived Alpha-1 Antitrypsin
Placebo inhaled
Placebo inhaled
Intervention: Aerosolized, human, plasma-derived Alpha-1 Antitrypsin
Outcomes
Primary Outcomes
Safety and airway inflammation
Time Frame: days 1,7,14,21,28,35,42,49,56,63
Secondary Outcomes
- Sputum microbiology, pulmonary function and serum CRP(days 1,7,14,21,28,35,42,49,56,63)