Clinical trial NCT02282527: A Study to Assess Safety and PK of Liquid Alpha₁-Proteinase Inhibitor (Human) in Treating Alpha₁-Antitrypsin Deficiency
Official title: A Multi-center, Randomized, Double-blind, Crossover Study to Assess the Safety and Pharmacokinetics of Liquid Alpha₁-Proteinase Inhibitor (Human) Compared to Prolastin®-C in Subjects With Alpha₁-Antitrypsin Deficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Alpha₁-Antitrypsin Deficiency
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2014-11-04
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Grifols Therapeutics Inc. conducted a multi-center, randomized, double-blind, crossover study to evaluate the safety, immunogenicity, and pharmacokinetics (PK) of Liquid Alpha₁-PI compared to the currently licensed product, Prolastin-C, in subjects with Alpha₁-Antitrypsin Deficiency (AATD).


Eligibility criteria: Inclusion Criteria:

* Be between 18 and 70 years of age, inclusive
* Had a diagnosis of congenital AATD
* Had a documented total alpha₁-PI level \< 11 µM. If the total alpha₁-PI level had yet to be documented, a blood draw for total alpha₁-PI level was obtained at the Screening Visit
* Had a post-bronchodilator Forced expiratory volume in 1 second (FEV1) ≥ 30% and \< 80% of predicted and FEV1/forced vital capacity (FVC) \< 70%
* If the subject had received alpha₁-PI augmentation therapy of any kind, he/she must have been be willing to discontinue that treatment at the Week 1 (Baseline) Visit and remain off any kind of alpha₁-PI treatment, other than the investigational products for this study, while participating in the study

Exclusion Criteria:

* Subject had a moderate or severe pulmonary exacerbation during the 4 weeks before the Week 1 (Baseline) Visit
* History of lung or liver transplant
* Any lung surgery during the past 2 years (excluding lung biopsy)
* Liver cirrhosis confirmed by biopsy
* Elevated liver enzymes (aspartate transaminase \[AST\], alanine aminotransferase \[ALT\], and alkaline phosphatase \[ALP\]) equal to or greater than 2.5 times the upper limit of normal
* Severe concomitant disease (e.g., congestive heart failure, clinically significant pulmonary fibrosis, malignant disease \[with the exception of skin cancers other than melanoma\], history of acute hypersensitivity pneumonitis reaction, or current chronic hypersensitivity pneumonitis)
* Females who were 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 abstinence) throughout the study
* Known previous infection with or clinical signs and symptoms consistent with current hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection
* Smoking during the past 6 months or a positive urine cotinine test at the Screening Visit that is due to smoking
* Participation in another investigational drug study within one month prior to the Week 1 (Baseline) Visit
* History of anaphylaxis or severe systemic response to any plasma-derived alpha1-PI preparation or other blood product(s)
* Use of 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 inhaled steroids are not considered systemic steroids)
* Use of systemic or aerosolized antibiotics for an exacerbation within the 4 weeks prior to the Week 1 (Baseline) Visit
* Known selective or severe Immunoglobulin A (IgA) deficiency

Primary outcomes:
measure: AUC(0-7 Days) Based on Antigenic Content
timeFrame: pre-dose, 0, 15 min, 30 min, 1 hour, 2 hours, 4 hours, 8 hours, 1 day, 2 days, 5 days, 7 days post dose
Secondary outcomes:
measure: AUC(0-7 Days) Based on Functional Activity
timeFrame: pre-dose, 0, 15 min, 30 min, 1 hour, 2 hours, 4 hours, 8 hours, 1 day, 2 days, 5 days, 7 days post dose
measure: Number of Subjects With Immunogenicity Response
timeFrame: Weeks 1, 9, 17, and 20
Other outcomes:
Locations:
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Gainesville
country: United States
facility: University of Florida Gainesville
state: Florida
city: Miami
country: United States
facility: University of Miami - Miller School of Medicine
state: Florida
city: Wilmington
country: United States
facility: PMG Research of Wilmington
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Tyler
country: United States
facility: University of Texas Health Science Center
state: Texas
Study officials:
References: