The main purpose of this study is to evaluate the efficacy of RYMPHYSIA \[Alpha1-Proteinase Inhibitor (Human)\] compared to another available alpha-1 proteinase Inhibitor (A1PI) in adults with A1PI deficiency and COPD-emphysema. In Part A of the study, participants will be randomly assigned to receive either RYMPHYSIA or another available A1PI for 104 weeks. Participants who were randomized to another available A1PI will enter a 2-week follow-up period after the treatment phase is completed; participants who were randomized to RYMPHYSIA will enter Part B. In Part B, participants will be randomly assigned to one of two groups and will receive either the same dose of RYMPHYSIA as in Part A or a different dose for an additional 104 weeks, followed by a 2-week follow-up period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
RYMPHYSIA administered through an IV injection.
Another available A1PI administered through an IV injection.
Part A: Annual Rate of Change in the Physiologically Adjusted Lung Density
Annual rate of the physiologically adjusted lung density change will be measured as the 15th percentile (PD15) of the lung density measurements as assessed by computed tomography (CT) densitometry at total lung capacity (TLC). CT lung density at the 15th percentile (PD15) is the threshold below which 15 percent (%) of the voxels have lower densities and is used as the parameter for estimating the rate of lung density decline.
Time frame: Up to Week 104
Part A: Annual Rate of Change in the Plasma Level of Elastin Degradation Products
The annual rate of change in the plasma levels of elastin degradation products (desmosine and isodesmosine) will be assessed to document the pharmacodynamic (PD) effect of RYMPHYSIA on the activity of neutrophil elastase using high-performance liquid chromatography-mass spectrometry (LC-MS). The assessment of elastin degradation products will be performed for participants in the RYMPHYSIA treatment arm only.
Time frame: Up to Week 104
Part A: Annual Rate of Change in the Plasma Level of Fibrinogen Degradation Products
The annual rate of change in the plasma levels of fibrinogen degradation products (Aα-Val360 fragments) will be assessed to document the PD effect of RYMPHYSIA on the activity of neutrophil elastase using high-performance LC-MS. The assessment of fibrinogen degradation products will be performed for participants in the RYMPHYSIA treatment arm only.
Time frame: Up to Week 104
Part A and Part B: Number of Moderate or Severe Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)
COPD exacerbations are defined as an acute worsening of respiratory symptoms that results in additional therapy and will be assessed based on the classification in GOLD criteria (2021). The assessment of COPD exacerbations will be performed for participants in the RYMPHYSIA treatment arm only.
Time frame: Part A, Part B: Up to Week 104
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Part A and Part B: Annual Rate of Change in the Post-bronchodilator Forced Expiratory Volume in One Second (FEV1)
FEV1 is the volume of air that can be forcefully exhaled in the first second after a full inspiration obtained by spirometry. Annual rate of change in the FEV1 will be assessed using spirometry. Spirometric measurements are to be performed in triplicate, and the highest value at each time point is to be used for analyses.
Time frame: Part A, Part B: Up to Week 104
Part A and Part B: Plasma Trough Level of Antigenic and Functional A1PI for RYMPHYSIA
Time frame: Part A, Part B: Pre- and post-dose at multiple timepoints (up to 144 hours) up to Week 104
Part A and Part B: Plasma Concentration of Antigenic and Functional A1PI for RYMPHYSIA
Time frame: Part A, Part B: Pre- and post-dose at multiple timepoints (up to 144 hours) up to Week 104
Part A and Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
The number of participants with TEAEs including drug-related AEs, serious AEs (SAEs), and temporally associated AEs will be assessed.
Time frame: Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)
Part A and Part B: Number of Participants Receiving RYMPHYSIA with Development of Post-treatment Immunogenicity as Measured by Anti-A1PI Binding and Neutralizing Antibodies
Serum samples will be analyzed for the presence of antibodies against A1PI using a validated anti-A1PI antibody detection (screening and confirmatory) assay at a qualified specialty laboratory. Samples with confirmed positive titers will be further analyzed for the presence of neutralizing antibodies using a validated neutralizing antibody assay at a qualified specialty laboratory.
Time frame: Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)
Part A and Part B: Changes in Laboratory Assessments
The number of participants who have normal/abnormal values at Baseline compared to normal/abnormal values post-Baseline will be assessed for hematology, clinical chemistry, and urinalysis.
Time frame: Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)
Part A and Part B: Changes in Vital Signs Measurement: Body Temperature
Percent change from Baseline to post Baseline will be assessed for body temperature.
Time frame: Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)
Part A and Part B: Changes in Vital Signs Measurement: Respiratory Rate
Percent change from Baseline to post Baseline will be assessed for respiratory rate.
Time frame: Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)
Part A and Part B: Changes in Vital Signs Measurement: Pulse Rate
Percent change from Baseline to post Baseline will be assessed for pulse rate.
Time frame: Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)
Part A and Part B: Changes in Vital Signs Measurement: Systolic and Diastolic Blood Pressure
Percent change from Baseline to post Baseline will be assessed for systolic and diastolic blood pressure.
Time frame: Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)
Part A and Part B: Number of Participants with Changes in Electrocardiogram (ECG) Measurements
Time frame: Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)
Part B: Annual Rate of Change in the Physiologically Adjusted Lung Density
The annual rate of the physiologically adjusted lung density change will be measured as the PD15 of the lung density measurements as assessed by CT densitometry at TLC. CT lung density at the PD15 is the threshold below which 15% of the voxels have lower densities and is used as the parameter for estimating the rate of lung density decline.
Time frame: Part B: Up to week 104