- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02001688
Phase II, Safety and Efficacy Study of Kamada-alpha-1-antitrypsin (AAT) for Inhalation"
December 31, 2019 updated by: Kamada, Ltd.
Phase II, Double-Blind, Placebo-Controlled Study to Explore the ELF and Plasma Concentration as Well as Safety of Inhaled Alpha-1 Antitrypsin in Alpha-1 Antitrypsin Deficiency Subjects
To evaluate different doses of "Kamada-AAT for Inhalation" on the levels of alpha 1-proteinase inhibitor and other analytes in epithelial lining fluid (ELF) and serum and to assess the safety of the treatment in subjects with AAT Deficiency.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
36
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Florida
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Gainesville, Florida, United States, 32610
- University of Florida, Pulmonary, Critical Care & Sleep Medicine
-
-
Texas
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Tyler, Texas, United States, 75708
- The University of Texas Health Science Center at Tyler Center for Clinical Research
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Male or female patients between 18 and 65 years of age (inclusive).
- Able and willing to sign informed consent.
- Males, and non-pregnant, non-lactating females whose screening pregnancy test is negative and who are using contraceptive methods deemed reliable by the investigator or who are post-menopausal or surgically sterilized.
- Diagnosis of alpha1-antitrypsin deficiency [only individuals with a ZZ or Z null classification].
- Forced expiratory volume in one second (FEV1) ≥ 50% of predicted post bronchodilator
- No respiratory exacerbations within 6 weeks of baseline. Subjects can be re-screened if exacerbations exist at the time of enrollment.
- No signs of chronic and/or acute Hepatitis A, Hepatitis B, Hepatitis C, HIV infection and Parvovirus B19, by NAT (for Parvovirus B19, nucleic acid testing (NAT) result must be < 10^4 IU/mL).
- No significant abnormalities in serum hematology, serum chemistry, serum inflammatory / immunogenic markers and urinalysis.
- No significant abnormalities in ECG.
- Not on intravenous augmentation therapy for at least 8 weeks prior to initial dosing with study drug/placebo and willing to forego intravenous augmentation therapy for the duration of the study.
Exclusion Criteria:
- Clinically significant intercurrent illnesses (except for respiratory or liver disease secondary to AAT deficiency), including: cardiac, hepatic, renal, endocrine, neurological, hematological, neoplastic, immunological, skeletal or other) that in the opinion of the investigator, could interfere with the safety, compliance or other aspects of this study. Patients with well-controlled, chronic diseases could possibly be included after consultation with the treating physician and the sponsor.
- History of life threatening allergy, anaphylactic reaction, or systemic response to human plasma derived products.
- History of life threatening transfusion reactions.
- History of lung transplant.
- Current or previous (up to 8 weeks from baseline) use of AAT augmentation therapy or by any other route
- Current use of oral or parenteral glucocorticoids in doses exceeding 10mg of prednisone daily or equivalent generics (substance and dose).
- Any lung surgery within the past two years.
- On any thoracic surgery waiting list.
- Active smoking during the last 12 months from screening date.
- Pregnancy or lactation.
- Woman of child-bearing potential not taking adequate contraception deemed reliable by the investigator.
- Presence of psychiatric/ mental disorder or any other medical disorder which might impair the patient's ability to give informed consent or to comply with the requirements of the study protocol.
- Evidence of alcohol abuse or history of alcohol abuse or illegal and/or legally prescribed drugs.
- Immunoglobulin A (IgA) Deficiency.
- Inability to undergo bronchoscopy.
- Allergy to lidocaine or any other medicines used in the bronchoscopy process
- Exacerbation of chronic obstructive pulmonary disease (COPD) in the previous 6 weeks.
- Participation in another clinical trial involving investigational medication or interventional treatment within 30 days prior to baseline visit.
- Participation in observational clinical trial which involves any invasive procedure scheduled to occur during the AAT inhaled study period. If participating in an observational clinical trial that already completed all diagnostic procedures (e.g. liver biopsy), any adverse events (AEs) experienced must have returned to baseline within 30 days prior to baseline visit.
- Inability to attend scheduled clinic visits and/or comply with the study protocol.
- Any other factor that, in the opinion of the investigator, would prevent the patient form complying with the requirements of the protocol.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Kamada-AAT for Inhalation, 80mg
Daily inhalation of Kamada-AAT for Inhalation, 80mg
|
|
Placebo Comparator: Placebo
Placebo administered by inhalation daily
|
|
Experimental: Kamada-AAT for Inhalation, 160mg
Daily inhalation of Kamada-AAT for Inhalation, 160mg
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in the Concentration of Antigenic Alpha-1 Antitrypsin (AAT) in the Lung Epithelial Lining Fluid (ELF)
Time Frame: 12 weeks from initiation of study drug
|
Patients underwent bronchoalveolar lavage (BAL) prior to initiation of drug and then again after 3 months.
Concentration of AAT in the BAL was measured by an enzyme linked immunosorbent assay (ELISA) specific for the normal form of AAT (piM).
Urea was also measured in order to determine the dilution factor of the BAL fluid and calculate the concentration of AAT in the ELF.
|
12 weeks from initiation of study drug
|
Change From Baseline to 12 Weeks in the Concentration of Functional AAT (Alpha-1 Antitrypsin) in ELF
Time Frame: 12 weeks from initiation of study drug
|
ITT population with baseline and 12 week values.
Patients underwent bronchoalveolar lavage (BAL) prior to initiation of drug and then again after 3 months.
Concentration of AAT in the BAL was measured by an antineutrophil elastase capacity (ANEC) assay.
Urea was also measured in order to determine the dilution factor of the BAL fluid and calculate the concentration of AAT in the ELF.
|
12 weeks from initiation of study drug
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Levels of M Specific AAT in Plasma (PiM)
Time Frame: 12 weeks from initiation of study drug
|
Intention to treat (ITT) population with baseline and 12 week values.The median change from baseline to Week 12 in the levels of M-specific AAT (piM) in plasma was measured using a specific ELISA assay for M-specific AAT (piM)
|
12 weeks from initiation of study drug
|
Change From Baseline in AAT-neutrophil Elastase (NE) Complexes in ELF
Time Frame: 12 weeks from initiation of study drug
|
Patients underwent a BAL procedure at baseline and 12 weeks and the fluid was analyzed to calculate the change from baseline in the concentration of complexes between AAT and neutrophil elastase in the ELF
|
12 weeks from initiation of study drug
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
April 1, 2014
Primary Completion (Actual)
February 1, 2016
Study Completion (Actual)
May 1, 2016
Study Registration Dates
First Submitted
November 24, 2013
First Submitted That Met QC Criteria
November 28, 2013
First Posted (Estimate)
December 5, 2013
Study Record Updates
Last Update Posted (Actual)
January 18, 2020
Last Update Submitted That Met QC Criteria
December 31, 2019
Last Verified
December 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- Kamada-AAT (inhaled)-006
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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