Brief Title
Efficacy and Safety Study of Augmentation Therapy With ARALAST Fraction IV-1 (Human Alpha 1 - Proteinase Inhibitor)
Official Title
The Effect of Augmentation Therapy With ARALAST Fraction IV-1 (ARALAST) Alpha1-Proteinase Inhibitor (α1-PI) on the Level of α1-PI and Other Analytes in the Bronchoalveolar (BAL) Epithelial Lining Fluid (ELF)
Brief Summary
The purpose of this study is to evaluate the effects of weekly augmentation therapy with
ARALAST Fraction IV-1 (Fr IV-1) on epithelial lining fluid (ELF) alpha 1-proteinase inhibitor
levels and other ELF analytes and to assess the safety of the treatment. Eligible subjects
with a diagnosis of severe congenital alpha 1-antitrypsin deficiency will receive 8
consecutive weekly treatments with 60 mg/kg/week of functional ARALAST Fr IV-1 administered
intravenously. The efficacy and safety assessments will include two bronchoscopies with
bronchoalveolar lavage on study initiation and on study termination and multiple imaging and
laboratory safety assessments. Each subject will participate for a minimum of 12 weeks.
Study Phase
Phase 4
Study Type
Interventional
Primary Outcome
Change in Bronchoalveolar Lavage (BAL) Epithelial Lining Fluid (ELF) Alpha1-Proteinase Inhibitor (α1-PI) Level
Secondary Outcome
Ratio of Post- to Pre-treatment BAL ELF Antineutrophil Elastase Capacity (ANEC) Levels
Condition
Alpha 1-Antitrypsin Deficiency
Intervention
Alpha1-Proteinase Inhibitor
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
21
Start Date
October 27, 2006
Completion Date
December 14, 2007
Primary Completion Date
December 14, 2007
Eligibility Criteria
Inclusion Criteria:
- Signed and dated informed consent.
- Male or female 18 years of age or older.
- Documented, endogenous serum α1-PI level < 40 mg/dL measured at screening (unless
otherwise approved by the Sponsor) after a minimum of 28-day washout of any prior
replacement therapy (if applicable).
- Phenotype Pi Z (which includes Pi*Z/Z, Pi*Z/Null, or Pi*Malton/Z), or Pi*Null/Null.
- Pulmonary functions at screening meeting the following criteria:
1. Forced expiratory volume at 1 second (FEV1) >= 50% of predicted value; or
2. FEV1 > 35% of predicted value and diffusing capacity for carbon monoxide > 45% of
predicated value, with no supplemental oxygen therapy and < 3 pulmonary
exacerbations or bronchitis requiring antibiotics/corticosteroids within the past
12 months).
- For any female of childbearing potential, a negative urine test for pregnancy within 7
days prior to the first bronchoalveolar lavage (BAL) visit and agreement to employ
adequate birth control measures for the duration of the study.
- No clinically significant abnormalities detected on a 12-lead electrocardiogram (ECG)
performed at the screening visit (ECG previously obtained within the past 12 months
may be used, if available).
- Laboratory results obtained at the screening visit, meeting the following criteria:
1. Serum alanine aminotransferase (ALT) <= 2 times upper limit of normal (ULN)
2. Serum aspartate aminotransferase (AST) <= 2 times ULN
3. Serum total bilirubin <= 2 times ULN
4. Proteinuria < +2 on dipstick analysis
5. Serum creatinine <= 1.5 times ULN
6. Absolute neutrophil count (ANC) >= 1500 cells/mm3
7. Hemoglobin (Hgb) >= 10.0 g/dL
8. Platelet count >= 105/mm3
- If the subject is treated with respiratory medications, such as inhaled
bronchodilators or inhaled corticosteroids, or other chronic medications for the
treatment of the subjects´s other medical condition(s), the subject's medication doses
were unchanged for at least 14 days prior to the baseline BAL visit.
Exclusion Criteria:
- Clinically significant pulmonary impairment, other than chronic pulmonary disease
(COPD).
- The subject has received any alpha 1 proteinase inhibitor (α1-PI) augmentation therapy
(e.g., Prolastin, Zemaira, Aralast, or an investigational α1-PI, by any route
including intravenous and inhaled) within 28 days prior to screening.
- The subject has received an investigational drug or device within 1 month prior to
screening, or the subject is currently receiving an investigational drug or device. If
the subject receives another investigational drug or device after enrollment, the
subjects is to be withdrawn from the trial.
- Presence of clinical symptoms of any lower respiratory tract infection or acute
pulmonary exacerbation within 14 days prior to screening.
- The subject has a known selective Immunoglobulin A (IgA) deficiency (IgA level less
than 15 mg/dL) and/or antibody against IgA.
- The subject is pregnant or lactating, or intends to become pregnant during the course
of the study.
- The subject is not a suitable candidate for a BAL procedure.
- Moderate or severe bronchiectasis (total daily sputum production > 10 mL).
- Clinically significant medical, psychiatric, or cognitive illness, or recreational
drug/alcohol use that, in the opinion of the investigator, would affect subject safety
or compliance.
- Prior history of adverse reaction to local anaesthetics, sedatives, pain control
drugs, and other medication employed at the study center for perioperative care
associated with the BAL procedure.
- Long-term use of oral or parenteral glucocorticosteroid within 28 days prior to
screening.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Study Director, ,
Location Countries
Australia
Location Countries
Australia
Administrative Informations
NCT ID
NCT00396006
Organization ID
460502
Responsible Party
Sponsor
Study Sponsor
Baxalta now part of Shire
Study Sponsor
Study Director, Study Director, Takeda
Verification Date
April 2021