IRB Study Number 21-1159
Status Recruiting
Phase Phase 2
Location Cleveland Clinic Main Campus
Institute Respiratory Institute
Description
The purpose of this study is to evaluate the safety and tolerability of 72 milligrams per kilogram (mg/kg) and 144 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).
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).
· Currently receiving Alpha1-PI augmentation therapy or has 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 at 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. Note: Subjects must not be naïve to Alpha1-PI augmentation therapy for study participation.
· 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.
