A Study of RYMPHYSIA for Alpha1-Proteinase Inhibitor (A1PI) Therapy in Adults With A1PI Deficiency and Chronic Obstructive Pulmonary Disease (COPD)-Emphysema

Phase 4

Withdrawn

• Conditions: Alpha1-Antitrypsin Deficiency; Chronic Obstructive Pulmonary Disease (COPD)
• Interventions: Biological: RYMPHYSIA; Biological: Another Available A1PI

• Registration Number: NCT05466747
• Lead Sponsor: Takeda

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-06-17
• Study First Submitted QC: 2022-07-18
• Study First Posted: 2022-07-20
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-02
• Last Update Posted: 2023-05-06
• Study Start: 2024-01-01
• Primary Completion: 2027-04-26
• Study Completion: 2029-05-07

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part A: RYMPHYSIA 60 mg/kg	RYMPHYSIA	Participants will receive 60 mg/kg RYMPHYSIA, intravenous (IV) infusion, once every week for up to 104 weeks.
Part A: Another Available A1PI 60 mg/kg	Another Available A1PI	Participants will receive 60 mg/kg of another available A1PI, IV infusion, once every week for up to 104 weeks.
Part B: RYMPHYSIA 60 mg/kg	RYMPHYSIA	Participants will receive 60 mg/kg RYMPHYSIA, IV infusion, once every week for up to 104 weeks.
Part B: RYMPHYSIA 120 mg/kg	RYMPHYSIA	Participants will receive 120 mg/kg RYMPHYSIA, IV infusion, once every week for up to 104 weeks.

Primary Outcome Measures

Name	Time	Method
Part A: Annual Rate of Change in the Physiologically Adjusted Lung Density	Up to Week 104	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.

Secondary Outcome Measures

Name	Time	Method
Part A: Annual Rate of Change in the Plasma Level of Elastin Degradation Products	Up to Week 104	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.
Part A: Annual Rate of Change in the Plasma Level of Fibrinogen Degradation Products	Up to Week 104	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.
Part A and Part B: Number of Moderate or Severe Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)	Part A, Part B: Up to Week 104	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.
Part A and Part B: Annual Rate of Change in the Post-bronchodilator Forced Expiratory Volume in One Second (FEV1)	Part A, Part B: Up to Week 104	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.
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	Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)	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.
Part A and Part B: Changes in Laboratory Assessments	Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)	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.
Part A and Part B: Changes in Vital Signs Measurement: Body Temperature	Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)	Percent change from Baseline to post Baseline will be assessed for body temperature.
Part A and Part B: Changes in Vital Signs Measurement: Respiratory Rate	Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)	Percent change from Baseline to post Baseline will be assessed for respiratory rate.
Part A and Part B: Changes in Vital Signs Measurement: Pulse Rate	Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)	Percent change from Baseline to post Baseline will be assessed for pulse rate.
Part A and Part B: Changes in Vital Signs Measurement: Systolic and Diastolic Blood Pressure	Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)	Percent change from Baseline to post Baseline will be assessed for systolic and diastolic blood pressure.
Part A and Part B: Number of Participants with Changes in Electrocardiogram (ECG) Measurements	Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)
Part A and Part B: Plasma Trough Level of Antigenic and Functional A1PI for RYMPHYSIA	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	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)	Part A, Part B: Up to 2 weeks after the last dose (Up to Week 106)	The number of participants with TEAEs including drug-related AEs, serious AEs (SAEs), and temporally associated AEs will be assessed.
Part B: Annual Rate of Change in the Physiologically Adjusted Lung Density	Part B: Up to week 104	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.