Safety and Pharmacokinetics of Alpha-1 Proteinase Inhibitor in Subjects With Alpha1-Antitrypsin Deficiency

Emphysema Clinical Trial

— SPARK  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01213043
• Other study ID #: T6004-201/Version 2
• Status: Completed
• Phase: Phase 2
• First received: September 29, 2010
• Last updated: April 8, 2013
• Start date: November 2010
• Est. completion date: January 2012

Study information

• Verified date: April 2013
• Source: Grifols Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alpha 1-Antitrypsin Deficiency
• Alpha 1-antitrypsin Deficiency (AATD)
• Emphysema

Intervention

Biological:
• Prolastin-C, 60 mg/kg
60 mg/kg weekly infusion of Prolastin-C for 8 weeks
• Prolastin-C, 120 mg/kg
120 mg/kg weekly infusion of Prolastin-C for 8 weeks

Locations

Country	Name	City	State
United States	Medical University of South Carolina, Division of Pulmonary and Critical Care Medicine	Charleston	South Carolina
United States	University of Florida College of Medicine	Gainesville	Florida
United States	University of Miami	Miami	Florida
United States	Temple University Hosptial/Temple Lung Center	Philadelphia	Pennsylvania
United States	The University of Texas Health Science Center at Tyler	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Grifols Therapeutics Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Subjects With Treatment-Emergent Adverse Events (TEAEs)	Number of subjects experiencing at least one TEAE. TEAEs were defined as any adverse event (AE) during the study that began on or after the date of first dose of investigational product (i.e., Prolastin-C).	22 weeks	Yes
Primary	Subjects With Drug-Related TEAE(s)	Number of subjects with at least one TEAE that was determined by the Investigator to be either "possibly related" or "related" to the investigational product (i.e., Prolastin-C).	22 weeks	Yes
Primary	Subjects With Treatment-Emergent Serious Adverse Events (SAEs)	Number of subjects who experienced at least one treatment-emergent SAE.	22 weeks	Yes
Primary	Subjects Withdrawn Due to an AE(s)	Number of subjects who were withdrawn from the study due to at least one AE.	22 weeks	Yes
Primary	Subjects With Treatment-Emergent Pulmonary Exacerbation(s)	Number of subjects with at least one treatment-emergent pulmonary exacerbation	22 weeks	Yes
Primary	Subjects With Severe TEAE(s) or Pulmonary Exacerbation(s)	Number of subjects who experienced at least one severe TEAE or pulmonary exacerbation.	22 weeks	Yes
Primary	Number of TEAEs	Total number of TEAEs reported.	22 Weeks	Yes
Primary	Number of Drug-related TEAEs	Total number of drug-related TEAEs reported	22 Weeks	Yes
Primary	Number of Treatment-Emergent Pulmonary Exacerbations	Total number of treatment-emergent pulmonary exacerbations.	22 Weeks	Yes
Secondary	AUC0-7days	Area Under the Alpha-1 PI Concentration-Time Curve from Day 0 to Day 7	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	No
Secondary	Mean Trough	The average trough concentration at steady-state, calculated as the mean value using the four Trough measurements obtained at Weeks 6, 7, 8 and at 7 days (168 hours) post infusion at Week 8 for the first treatment period or prior to the start of the infusions at Weeks 16, 17, 18, and at 7 days (168 hours) post infusion at Week 18 for the second treatment period.	Single measurment immediately prior to infusion at Weeks 6, 7, 8, 9 and Weeks 16, 17, 18, 19	No