Safety and Pharmacokinetics of Alpha-1 Proteinase Inhibitor in Subjects With Alpha1-Antitrypsin Deficiency
A Randomized Double-blind Crossover Study to Assess the Safety and Pharmacokinetics of Two Different Doses of Weekly Intravenous Administration of Alpha1-Proteinase Inhibitor (Human) Prolastin®-C in Subjects With Alpha1-Antitrypsin Deficiency
This is a study to assess the safety and pharmacokinetics of weekly infusions of 120 mg/kg of Prolastin-C (alpha1-proteinase inhibitor [alpha1-PI] [Human]), compared to weekly infusions of 60 mg/kg of Prolastin-C in patients with alpha 1-antitrypsin deficiency (AATD).
The question of whether higher doses of alpha1-PI (>60 mg/kg) are able to provide better protection to patients with alpha 1-antitrypsin deficiency is currently unknown. As a first step to address this question, the present study has been undertaken. This is a multi-center, randomized, double-blind, crossover study to assess the safety and pharmacokinetics of weekly infusions of 120 mg/kg of Prolastin-C, compared to weekly infusions of 60 mg/kg of Prolastin-C in patients with alpha 1-antitrypsin deficiency. This study is a crossover design with 2 treatment sequences: Treatment Sequence 1: 60 mg/kg weekly infusion of Prolastin-C for 8 weeks followed by 120 mg/kg weekly infusion of Prolastin-C for 8 weeks (starting at Week 1) (total of 16 treatment weeks) Treatment Sequence 2: 120 mg/kg weekly infusion of Prolastin-C for 8 weeks followed by 60 mg/kg weekly infusion of Prolastin-C for 8 weeks (starting at Week 11) (total of 16 treatment weeks) Approximately 15 subjects are planned to be entered into each treatment sequence. At Weeks 8 to 11 and Weeks 18 to 21, a total of 15 serial blood samples for each subject will be drawn for pharmacokinetic analysis. The expected duration of the study subject's participation will be approximately 25 weeks (which includes a 3-Week Screening Phase, 2-Week Washout Period [between different alpha-1 PI treatment doses], and a 4-Week Follow-up Period). The following safety parameters will be assessed: adverse events, pulmonary exacerbations, vital signs, pulmonary function tests, and clinical laboratory tests.
Subjects With Treatment-Emergent Adverse Events (TEAEs)
Prolastin-C, 60 mg/kg
Study Arms / Comparison Groups
Prolastin-C, 60 mg/kg
Description: 60 mg/kg weekly infusion of Prolastin-C for 8 weeks. Subjects were infused with 60 mg/kg Prolastin-C by means of one of two possible treatment sequences: 1) 60 mg/kg weekly infusion of Prolastin-C for 8 weeks followed by 120 mg/kg Prolastin-C for 8 weeks, or 2) 120 mg/kg Prolastin-C for 8 weeks followed by 60 mg/kg weekly infusion of Prolastin-C for 8 weeks (total of 16 weeks).
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Primary Completion Date
Inclusion Criteria: - Be between 18 and 70 years of age - Have a documented diagnosis of congenital AATD - Have a post-bronchodilator Forced Expired Volume in 1 second (FEV1) of ≥30% and <80% and FEV1/forced vital capacity (FVC) <70% - If receiving alpha-1 PI augmentation therapy, be willing to discontinue the treatment for the duration of the study Exclusion Criteria: - Had a moderate or severe pulmonary exacerbation during the 4 weeks before the study - History of lung or liver transplant - Any lung surgery during the past 2 years - Confirmed liver cirrhosis - Elevated liver enzymes - Severe concurrent disease - Females who are pregnant or breast-feeding or unwilling to practice effective contraception during the study - Infection with hepatitis A, B, or C, human immunodeficiency or parvovirus B19 - Smoking during the past 6 months - Use of systemic steroids within 4 weeks of the study - Use of antibiotics for an exacerbation within 4 weeks of the study
18 Years - 70 Years
Accepts Healthy Volunteers
Mark Brantly, MD, ,
Grifols Therapeutics LLC
Mark Brantly, MD, Principal Investigator, University of Florida