The purpose of the study is 2-fold: (1) to evaluate the safety and potential immunogenicity of GLASSIA following intravenous (IV) administration via in-line filtration; and (2) to assess the effects of GLASSIA augmentation therapy on the levels of A1PI and various biomarkers in the epithelial lining fluid (ELF) following intravenous (IV) administration at a dosage of 60 milligrams per kilogram (mg/kg) Body weight (BW)/week active alpha1-proteinase inhibitor (A1PI) protein for 25 weeks in participants with emphysema due to congenital A1PI deficiency.

Inclusion Criteria:

1. Male or female participants meeting the following age criteria:

   1. For participants who will undergo bronchoscopy/ bronchoalveolar lavage (BAL) procedures: 18 to 75 years of age at the time of screening.
   2. For participants who will be waived from undergoing bronchoscopy/BAL procedures: 18 years of age or older at the time of screening.

2. Documented Alpha1-Proteinase Inhibitor (A1PI) genotype of Pi*Z/Z, Pi*Z/Null, Pi*Malton/Z, Pi*Null/Null, or other "at-risk" allelic combinations such as SZ (excluding MS and MZ without the presence of another allowable at-risk genotype) and an endogenous A1PI plasma levels of less than or equal to (< or =)11 micrometer (μM) (< or = 0.572 milligrams per milliliter [mg/mL]).

3. Screening levels of endogenous plasma (antigenic) A1PI of < or =11 μM may be collected at any time during the screening period for treatment-naive participants, or following a 4 week minimum wash-out from previous augmentation therapy in treatment-experienced participants.

4. Participants must have at least one of the following: clinical diagnosis of emphysema, evidence of emphysema on computerized tomography (CT) scan of the chest, and/or evidence of airway obstruction which is not completely reversed with bronchodilator treatment at the time of screening.

5. If the participant is being treated with any respiratory medications including inhaled bronchodilators, inhaled anticholinergics, inhaled corticosteroids, or low-dose systemic corticosteroids (prednisone < or =10 milligram per day (mg/day) or its equivalent), the doses of the participant's medications have remained unchanged for at least 14 days prior to screening.

6. The participant is a nonsmoker or has ceased smoking for a minimum of 13 weeks prior to screening (serum cotinine level at screening within normal range of a nonsmoker) and agrees to refrain from smoking throughout the course of the study. Participants with a positive cotinine test due to nicotine replacement therapy (example [eg], patches, chewing gum), vapor cigarettes, or snuff are eligible.

7. If female of childbearing potential, the participant presents with a negative pregnancy test at screening and agrees to employ adequate birth control measures for the duration of the study.

8. The participant is willing and able to comply with the requirements of the protocol.

9. The participant must have pulmonary function at the time of screening meeting both of the following:

   1. Post-bronchodilator forced expiratory volume in 1 second (FEV1) greater than or equal to (> or =) 50 percentage (%) of predicted.
   2. If FEV1 is >80% predicted, then FEV1/forced vital capacity (FVC) must be <0.7. *Note: Inclusion criterion #1a, #9a and #9b are not applicable to participants who are not required to undergo the bronchoscopy/BAL procedures.

Exclusion Criteria:

1. The participant is experiencing or has a history of clinically significant pulmonary disease (other than chronic obstructive pulmonary disease (COPD), emphysema, chronic bronchitis, mild bronchiectasis, and stable asthma).

2. The participant is experiencing or has a history of chronic severe cor pulmonale (resting mean pulmonary artery pressure > or =40 millimeters) of mercury [mm Hg]).

3. The participant routinely produces more than 1 tablespoon of sputum per day.

4. The participant has a history of frequent pulmonary exacerbations (greater than 2 moderate or severe exacerbations within 52 weeks prior to screening.

5. The participant is experiencing a pulmonary exacerbation at the time of screening (participant may be rescreened 4 weeks after the clinical resolution of an exacerbation).

6. The participant has clinically significant abnormalities (other than emphysema, chronic bronchitis, or mild bronchiectasis) detected on chest X-ray or CT scan at the time of screening (past records obtained within 52 weeks prior to screening may be used, if available).

7. The participant has clinically significant abnormalities detected on a 12-lead electrocardiogram (ECG) performed at the time of screening (past records obtained within 26 weeks prior to screening may be used, if available).

8. The participant has clinically significant congestive heart failure with New York Heart Association (NYHA) Class III/IV symptoms.

9. The participant is experiencing an active malignancy or has a history of malignancy within 5 years prior to screening, with the exception of the following: adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or stable prostate cancer not requiring treatment.

10. The participant has a history of lung or other organ transplant, is currently on a transplant list, or has undergone major lung surgery.

11. The participant is receiving long-term around-the-clock oxygen (O2) supplementation. (The following are allowed: short-term use of oxygen supplementation [eg, for the management of acute COPD exacerbation], O2 supplementation required during night time only, and supplemental O2 with continuous positive airway pressure [CPAP] or bi-level positive airway pressure [BiPAP]).

12. Known history of hypersensitivity following infusions of human blood or blood components.

13. Immunoglobulin A (IgA) deficiency (<8 milligram per deciliter (mg/dL) at screening).

14. Abnormal clinical laboratory results obtained at the time of screening meeting any of the following criteria:

    1. Serum alanine aminotransferase (ALT) >3.0 times upper limit of normal (ULN)
    2. Serum total bilirubin >2.0 times ULN
    3. >2+proteinuria on urine dipstick analysis
    4. Serum creatinine >2.0 times ULN
    5. Absolute neutrophil count (ANC) <1500 cells per cubic millimeter (cells/mm^3)
    6. Hemoglobin (Hgb) <9.0 gram per deciliter (g/dL)
    7. Platelet count <100,000/cubic millimeter (mm^3)

15. Ongoing active infection with hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) Type 1 or 2 infection at the time of screening.

16. The participant has any clinically significant medical, psychiatric, or cognitive illness, or any other uncontrolled medical condition (eg, unstable angina, transient ischemic attack) that, in the opinion of the investigator, would impede the participant's ability to comply with the study procedures, pose increased risk to the participant's safety, or confound the interpretation of study results.

17. The participant has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or device during the course of this study.

18. The participant is a family member or employee of the investigator.

19. If female, the participant is nursing at the time of screening.

    Note: Exclusion criteria #20, #21, #22, #23, and #24 are not applicable to participants who are not required to undergo the bronchoscopy/BAL procedures.

20. The participant has contraindication(s) to bronchoscopy such as recent myocardial infarction, unstable angina, other cardiopulmonary instability, tracheal obstruction or stenosis, moderate to severe hypoxemia or any degree of hypercapnia, unstable asthma, Stage 4 or 5 chronic kidney disease, pulmonary hypertension, severe hemorrhagic diathesis, and cervical C1/C2 arthritis.

21. The participant has had lung surgery which may interfere with bronchoscopy.

22. Known history of allergic/hypersensitivity reactions to medications used during and for perioperative care associated with the bronchoscopy/BAL procedures, such as local anesthetics, sedatives, pain control medications.

23. The participant is receiving or requires long-term (>4 weeks) immunosuppressive therapy, such as systemic corticosteroids at doses greater than 10 mg/day of prednisone (or its equivalent), mycophenolate mofetil, azathioprine, cyclophosphamide, and rituximab.

24. If a participant is receiving anticoagulant or anti-platelet therapy (such as warfarin and clopidogrel), the participant is unwilling to or unable to safely discontinue anticoagulant or anti-platelet therapy within 7 days prior to until at least 24 hours after the BAL procedures. An exception is low-dose aspirin alone which is allowed.

Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.