Alpha1-Antitrypsin Deficiency
Conditions
Keywords
Pulmonary Emphysema, Alpha-1 Antitrypsin Deficiency, AATD, Alpha-1 PI Deficiency, Alpha-1 Proteinase Inhibitor, Emphysema, Pathologic Processes, Pulmonary Disease, Chronic Obstructive, Lung Diseases, Obstructive, Lung Diseases, Respiratory Tract Diseases, Liver Diseases, Digestive System Diseases, Genetic Diseases, Inborn, Subcutaneous Emphysema, Alpha1-Antitrypsin, Trypsin Inhibitors, Serine Proteinase Inhibitors, Protease Inhibitors, Enzyme Inhibition, Molecular Mechanisms of Pharmacological Action
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).
Interventions
BIOLOGICALAlpha-1 15%
Alpha1-Proteinase Inhibitor (Human), 15%, Subcutaneous infusion
Intravenous infusion
Sponsors
Grifols Therapeutics LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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 |
| Immunogenicity: Number of Participants With Alpha1-PI Antibodies | Treatment Period 1- Single-Dose Week 1; Treatment Period 2- Repeat-Dose Weeks 1 and 9 |
Countries
United States
Outcome results
None listed