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.

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.

The data from the study shall be published (if applicable) by the sponsor. The investigators and the steering committee may be involved if agreed to by the sponsor. Neither the investigator nor any other person within his/her institution has the right to publish separately or individually without permission by the sponsor.