Brief Title
Safety and Pharmacokinetics of Alpha-1 Proteinase Inhibitor in Subjects With Alpha1-Antitrypsin Deficiency
Official Title
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
Brief Summary
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).
Detailed Description
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Subjects With Treatment-Emergent Adverse Events (TEAEs)
Secondary Outcome
AUC0-7days
Condition
Emphysema
Intervention
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).
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
30
Start Date
November 2010
Completion Date
January 2012
Primary Completion Date
January 2012
Eligibility Criteria
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
Gender
All
Ages
18 Years - 70 Years
Accepts Healthy Volunteers
No
Contacts
Mark Brantly, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01213043
Organization ID
T6004-201/Version 2
Responsible Party
Sponsor
Study Sponsor
Grifols Therapeutics LLC
Study Sponsor
Mark Brantly, MD, Principal Investigator, University of Florida
Verification Date
April 2013