Clinical trial NCT01213043: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Emphysema
Alpha 1-antitrypsin Deficiency (AATD)
Keywords: emphysema
alpha 1-antitrypsin
alpha 1-antitrypsin deficiency (AATD)
alpha 1-proteinase inhibitor (Alpha-1 PI)
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2010-10-01
Enrollment: 30
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: 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.

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

Primary outcomes:
measure: Subjects With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: 22 weeks
measure: Subjects With Drug-Related TEAE(s)
timeFrame: 22 weeks
measure: Subjects With Treatment-Emergent Serious Adverse Events (SAEs)
timeFrame: 22 weeks
measure: Subjects Withdrawn Due to an AE(s)
timeFrame: 22 weeks
measure: Subjects With Treatment-Emergent Pulmonary Exacerbation(s)
timeFrame: 22 weeks
measure: Subjects With Severe TEAE(s) or Pulmonary Exacerbation(s)
timeFrame: 22 weeks
measure: Number of TEAEs
timeFrame: 22 Weeks
measure: Number of Drug-related TEAEs
timeFrame: 22 Weeks
measure: Number of Treatment-Emergent Pulmonary Exacerbations
timeFrame: 22 Weeks
Secondary outcomes:
measure: AUC0-7days
timeFrame: Week 8 and Week 18 at the following timepoints: 0 (pre-infusion), completion of first infusion bag, completion of 2nd infusion bag, and 15 min, 30 min, and 1, 2, 4, 8, 24, 48, 120, and 168 hours post-dose
measure: Mean Trough
timeFrame: Single measurment immediately prior to infusion at Weeks 6, 7, 8, 9 and Weeks 16, 17, 18, 19
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Philadelphia
country: United States
facility: Temple University Hosptial/Temple Lung Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina, Division of Pulmonary and Critical Care Medicine
state: South Carolina
city: Tyler
country: United States
facility: The University of Texas Health Science Center at Tyler
state: Texas
Study officials:
affiliation: University of Florida
name: Mark Brantly, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Miami
name: Michael Campos, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Temple University Hospital/Temple Lung Center
name: Friedrich Kueppers, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of Texas Health Science Center at Tyler
name: James Stocks, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of South Carolina, Division of Pulmonary and Critical Care Medicine
name: Charlie Strange, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Willis T, Wee K, Mohn G. A high-purity Alpha-1 proteinase inhibitor from human plasma, TAL6004. Proceeding of the 19th European Respiratory Society Annual Congress; 2009 Sep 12-16; Vienna, Austria. Abstracts;34:S53.