- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01213043
Safety and Pharmacokinetics of Alpha-1 Proteinase Inhibitor in Subjects With Alpha1-Antitrypsin Deficiency (SPARK)
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 Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Florida
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Gainesville, Florida, United States, 32610-0225
- University of Florida College of Medicine
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Miami, Florida, United States, 33136
- University of Miami
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19140
- Temple University Hosptial/Temple Lung Center
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South Carolina
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Charleston, South Carolina, United States, 29425-6300
- Medical University of South Carolina, Division of Pulmonary and Critical Care Medicine
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Texas
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Tyler, Texas, United States, 75708
- The University of Texas Health Science Center at Tyler
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Prolastin-C, 60 mg/kg
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).
|
60 mg/kg weekly infusion of Prolastin-C for 8 weeks
Other Names:
|
Experimental: Prolastin-C, 120 mg/kg
120 mg/kg weekly infusion of Prolastin-C for 8 weeks.
Subjects were infused with 120 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).
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120 mg/kg weekly infusion of Prolastin-C for 8 weeks
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Subjects With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: 22 weeks
|
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).
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22 weeks
|
Subjects With Drug-Related TEAE(s)
Time Frame: 22 weeks
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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).
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22 weeks
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Subjects With Treatment-Emergent Serious Adverse Events (SAEs)
Time Frame: 22 weeks
|
Number of subjects who experienced at least one treatment-emergent SAE.
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22 weeks
|
Subjects Withdrawn Due to an AE(s)
Time Frame: 22 weeks
|
Number of subjects who were withdrawn from the study due to at least one AE.
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22 weeks
|
Subjects With Treatment-Emergent Pulmonary Exacerbation(s)
Time Frame: 22 weeks
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Number of subjects with at least one treatment-emergent pulmonary exacerbation
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22 weeks
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Subjects With Severe TEAE(s) or Pulmonary Exacerbation(s)
Time Frame: 22 weeks
|
Number of subjects who experienced at least one severe TEAE or pulmonary exacerbation.
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22 weeks
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Number of TEAEs
Time Frame: 22 Weeks
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Total number of TEAEs reported.
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22 Weeks
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Number of Drug-related TEAEs
Time Frame: 22 Weeks
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Total number of drug-related TEAEs reported
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22 Weeks
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Number of Treatment-Emergent Pulmonary Exacerbations
Time Frame: 22 Weeks
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Total number of treatment-emergent pulmonary exacerbations.
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22 Weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
AUC0-7days
Time Frame: 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
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Area Under the Alpha-1 PI Concentration-Time Curve from Day 0 to Day 7
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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
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Mean Trough
Time Frame: Single measurment immediately prior to infusion at Weeks 6, 7, 8, 9 and Weeks 16, 17, 18, 19
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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.
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Single measurment immediately prior to infusion at Weeks 6, 7, 8, 9 and Weeks 16, 17, 18, 19
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Michael Campos, MD, University of Miami
- Principal Investigator: Friedrich Kueppers, MD, Temple University Hospital/Temple Lung Center
- Principal Investigator: James Stocks, MD, The University of Texas Health Science Center at Tyler
- Principal Investigator: Charlie Strange, MD, Medical University of South Carolina, Division of Pulmonary and Critical Care Medicine
Publications and helpful links
General Publications
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Respiratory Tract Diseases
- Lung Diseases
- Liver Diseases
- Genetic Diseases, Inborn
- Lung Diseases, Obstructive
- Pulmonary Disease, Chronic Obstructive
- Subcutaneous Emphysema
- Pulmonary Emphysema
- Emphysema
- Alpha 1-Antitrypsin Deficiency
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Serine Proteinase Inhibitors
- Trypsin Inhibitors
- Protease Inhibitors
- Alpha 1-Antitrypsin
Other Study ID Numbers
- T6004-201/Version 2
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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