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The purpose of this study is to evaluate the safety and tolerability of 72 milligrams per kilogram (mg/kg) and 180 mg/kg Alpha-1 15%, administered as a single-dose subcutaneous (SC) infusion and subsequently as weekly SC infusions over 8 weeks in participants with Alpha1-Antitrypsin Deficiency (AATD).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: Treatment Period 1 (Alpha-1 15%, 72 mg/kg) | Experimental | Participants will receive Alpha-1 15% 72 mg/kg, single weekly subcutaneous (SC) infusion in treatment-period 1 (Single-Dose) at Week 1. |
|
| Cohort 1: Single-Dose Data Evaluation Period (Liquid Alpha 1-Proteinase Inhibitor 60 mg/kg) | Experimental | Following treatment period 1, participants in Cohort 1 will enter 21 days of washout/serial pharmacokinetic (PK) phase and then the single-dose data evaluation period. During the single-dose data evaluation phase, Liquid Alpha1- Proteinase Inhibitor (PI) 60 mg/kg, weekly intravenous (IV) Infusions will be administered from intravenous-dose Week 1 (single-dose Week 5) for up to Week 78, with the last IV dose given 1 week prior to the first repeat Alpha-1 15% SC dose. |
|
| Cohort 1: Treatment Period 2 (Alpha-1 15%, 72 mg/kg) | Experimental | Following treatment period 1 and single-dose data evaluation period, participants in Cohort 1 will enter treatment period 2 (Repeat-Dose) and will receive Alpha-1 15% 72 mg/kg, for 8 weekly SC infusions. |
|
| Cohort 2: Treatment Period 1 (Alpha-1 15%, 180 mg/kg) | Experimental | Participants will receive Alpha-1 15% 180 mg/kg, single weekly SC infusion in treatment-period 1 (Single-Dose) at Week 1. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alpha-1 15% | Biological | Alpha1-Proteinase Inhibitor (Human), 15%, Subcutaneous infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | Up to 668 days | |
| Number of Participants With Suspected Adverse Drug Reactions (ADRs) | Up to 668 days | |
| Number of Participants With Infusion Site Reactions | Up to 668 days | |
| Number of Participants With Serious Adverse Events (SAEs) | Up to 668 days | |
| Number of Participants With AEs and SAEs Leading to Discontinuation | Up to 668 days | |
| Number of Participants With Chronic Obstructive Pulmonary Disease (COPD) Exacerbations | Up to 668 days | |
| Number of Participants With Clinically Significant Abnormalities in Vital Signs (Heart Rate, Blood Pressure, Respiratory Rate, and Temperature) | Up to 668 days | |
| Change from Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Up to 668 days | |
| Change from Baseline in Forced Vital Capacity (FVC) | Up to 668 days | |
| Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters (Chemistry, Hematology, Urinalysis) | Up to 668 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCLA Medical Center | Los Angeles | California | 90025 | United States | ||
| University of Florida |
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| Cohort 2: Single-Dose Data Evaluation Period (Liquid Alpha1-Proteinase Inhibitor 120 mg/kg) | Experimental | Following treatment period 1, participants in Cohort 2 will enter 21 days of washout/serial pharmacokinetic (PK) phase and then the single-dose data evaluation phase. During the single-dose data evaluation phase, Liquid Alpha1-PI 120 mg/kg, weekly IV Infusions will be administered from intravenous-dose Week 1 (single-dose Week 5) for up to Week 78, with the last IV dose given 1 week prior to the first repeat Alpha-1 15% SC dose. |
|
| Cohort 2: Treatment Period 2 (Alpha-1 15%, 180 mg/kg) | Experimental | Following treatment period 1 and single-dose data evaluation phase, participants in Cohort 2 will enter treatment period 2 (Repeat-Dose) and will receive Alpha-1 15% 180 mg/kg, for 8 weekly SC infusions. |
|
| Liquid Alpha1-Proteinase Inhibitor (Human) | Biological | Intravenous infusion |
|
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| Immunogenicity: Number of Participants With Alpha1-PI Antibodies | Treatment Period 1- Single-Dose Week 1; Treatment Period 2- Repeat-Dose Weeks 1 and 9 |
| Gainesville |
| Florida |
| 32610 |
| United States |
| University of Miami | Miami | Florida | 33136 | United States |
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
| Medical University of South Carolina - Children's Hospital | Charleston | South Carolina | 29425 | United States |
| ID | Term |
|---|---|
| D019896 | alpha 1-Antitrypsin Deficiency |
| D011656 | Pulmonary Emphysema |
| D004646 | Emphysema |
| D010335 | Pathologic Processes |
| D029424 | Pulmonary Disease, Chronic Obstructive |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D030342 | Genetic Diseases, Inborn |
| D013352 | Subcutaneous Emphysema |
| ID | Term |
|---|---|
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
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| ID | Term |
|---|---|
| C088172 | 15-keto-17-phenyl-18,19,20-trinorprostaglandin F2 alpha-1-isopropyl ester |
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