A Study to Evaluate Safety, Tolerability and Pharmacokinetics of Two Different Doses of Alpha1-Proteinase Inhibitor Subcutaneous (Human) 15% in Participants with Alpha1-Antitrypsin Deficiency
Phase 1
Active, not recruiting
- Conditions
- Alpha1-Antitrypsin Deficiency
- Interventions
- Biological: Liquid Alpha1-Proteinase Inhibitor (Human)
- Registration Number
- NCT04722887
- Lead Sponsor
- Grifols Therapeutics LLC
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 16
Inclusion Criteria
- Have a diagnosis of congenital Alpha1-antitrypsin deficiency (AATD) with an allelic combination of ZZ, SZ, Z(null), (null)(null), S(null), or "at-risk" alleles (subjects with "at-risk" alleles must be individually evaluated for eligibility by the Medical Monitor).
- Have a documented pre-Alpha1-Proteinase Inhibitor (PI) augmentation therapy serum alpha-1 antitrypsin (AAT) level <11 micrometer (μM) (80 milligrams per decilitre (mg/dL) if measured by radial immunodiffusion or 50 mg/dL if measured by nephelometry).
- Subjects may be naïve to Alpha1-PI augmentation therapy or may be currently receiving Alpha1-PI augmentation therapy or received Alpha1-PI augmentation therapy within the past. If the subject is currently receiving Alpha1-PI augmentation therapy of any kind, he/she must be willing to discontinue that treatment for at least 25 days prior to the Week 1 (Baseline) Visit and remain off any kind of Alpha1-PI treatment, other than the IPs for this study, while participating in the study.
- At the Screening Visit, have a post-bronchodilator forced expiratory volume (FEV1) ≥30% and <80% of predicted and FEV1/forced vital capacity (FVC) <70% (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II or III).
Exclusion Criteria
- Have had a moderate or severe Chronic obstructive pulmonary disease (COPD) exacerbation during the 4 weeks before the Week 1 (Baseline) Visit.
- Have history of lung or liver transplant.
- Have any lung surgery during the past 2 years (excluding lung biopsy).
- Have severe concomitant disease (example, congestive heart failure, clinically significant pulmonary fibrosis, malignant disease [except for skin cancers other than melanoma], history of acute hypersensitivity pneumonitis reaction, or current chronic hypersensitivity pneumonitis).
- Females who are pregnant, breastfeeding or, if of child-bearing potential, unwilling to practice a highly effective method of contraception (oral, injectable, or implanted hormonal methods of contraception, placement of an intrauterine device (IUD) or intrauterine system (IUS), condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or true abstinence) throughout the study.
- Have smoked during the past 6 months or a positive urine cotinine test at the Screening Visit that is due to smoking.
- Participate in another Investigational product (IP) study within one month prior to the Week 1 (Baseline) Visit.
- Have history of anaphylaxis or severe systemic response to any plasma-derived Alpha1-PI preparation or other blood product(s).
- Use systemic steroids above a stable dose equivalent to 5 mg/day prednisone (i.e., 10 mg every 2 days) within the 4 weeks prior to the Week 1 (Baseline) Visit. It is recommended to maintain the same dose throughout the study.
- Use systemic or aerosolized antibiotics for a chronic COPD exacerbation within the 4 weeks prior to the Week 1 (Baseline) Visit.
- Have known selective or severe Immunoglobulin A (IgA) deficiency.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 2: Single-Dose Data Evaluation Period (Liquid Alpha1-Proteinase Inhibitor 120 mg/kg) Liquid Alpha1-Proteinase Inhibitor (Human) 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 1: Treatment Period 2 (Alpha-1 15%, 72 mg/kg) Alpha-1 15% 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 1: Single-Dose Data Evaluation Period (Liquid Alpha 1-Proteinase Inhibitor 60 mg/kg) Liquid Alpha1-Proteinase Inhibitor (Human) 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 2: Treatment Period 1 (Alpha-1 15%, 180 mg/kg) Alpha-1 15% Participants will receive Alpha-1 15% 180 mg/kg, single weekly SC infusion in treatment-period 1 (Single-Dose) at Week 1. Cohort 1: Treatment Period 1 (Alpha-1 15%, 72 mg/kg) Alpha-1 15% Participants will receive Alpha-1 15% 72 mg/kg, single weekly subcutaneous (SC) infusion in treatment-period 1 (Single-Dose) at Week 1. Cohort 2: Treatment Period 2 (Alpha-1 15%, 180 mg/kg) Alpha-1 15% 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.
- Primary Outcome Measures
Name Time Method 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 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 AEs and SAEs Leading to Discontinuation 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 Immunogenicity: Number of Participants With Alpha1-PI Antibodies Treatment Period 1- Single-Dose Week 1; Treatment Period 2- Repeat-Dose Weeks 1 and 9 Number of Participants With Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Up to 668 days Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters (Chemistry, Hematology, Urinalysis) Up to 668 days
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (6)
Dignity Health-St. Joseph's Hospital & Medical Center
🇺🇸Phoenix, Arizona, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
University of Florida
🇺🇸Gainesville, Florida, United States
University of Miami
🇺🇸Miami, Florida, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Medical University of South Carolina - Children's Hospital
🇺🇸Charleston, South Carolina, United States