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

Conditions: Alpha1-Antitrypsin Deficiency

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).


Eligibility criteria:
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.

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