Pharmacokinetic Study of ARALAST (Human Alpha1- PI)

April 17, 2021 updated by: Baxalta now part of Shire

Single-Dose, Double-Blind, Crossover Study to Evaluate the Pharmacokinetic Comparability of ARALAST Fraction IV-1 Alpha1-Proteinase Inhibitor (ARALAST Fr. IV-1) and ARALAST

The primary purpose of this study is to characterize the pharmacokinetic profile of intravenous Aralast Fraction (Fr.) IV-1, a sterile, stable, lyophilized preparation of functionally intact human Alpha1- Proteinase Inhibitor (α1-PI). This pharmacokinetic study will be a randomized controlled clinical trial with a cross-over design. Twenty-four subjects will be enrolled into the study. Overall study duration will be approximately 6-8 months.

Study Overview

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • South Australia
      • Adelaide, South Australia, Australia
      • Woodville, South Australia, Australia
    • Victoria
      • Fitzroy, Victoria, Australia
    • Western Australia
      • Nedlands, Western Australia, Australia
      • Christchurch, New Zealand
      • Hamilton, New Zealand
    • Auckland
      • Otahuhu, Auckland, New Zealand

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • The subject or subject´s legally authorized representative has provided written informed consent
  • Subject is 18 years of age or older
  • Subject has a documented, endogenous plasma Alpha1-PI level < 8 Micromolar
  • Subject is of the genotype Pi*Z/Z, Pi*Z/Null, Pi*Null/Null, Pi*Malton/Z, or others, dependent on the approval by the Sponsor
  • If the subject is female or of childbearing potential, the subject has a negative urine test for pregnancy within 7 days prior to first study product administration and agrees to employ adequate birth control measures for the duration of the study
  • Laboratory results obtained at the screening visit, meeting the following criteria:

    • Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) <= 2 times the upper limit of normal (ULN)
    • Serum total bilirubin <= 2 times ULN
    • Proteinuria < +2 on dipstick analysis
    • Serum creatinine <= 1.5 times ULN
    • Absolute neutrophil count (ANC) >= 1500 cells/mm3
    • Hemoglobin >= 10.0 g/dL
    • Platelet count >= 10^5/mm3
  • If the subject is treated with any respiratory medications, including inhaled bronchodilators and inhaled or oral corticosteroids, the subjects´ medication doses were unchanged for at least 14 days prior to first study product administration
  • Nonsmoker for a minimum of 3 months prior to first study product administration

Exclusion Criteria:

  • The subject has received any Alpha1-PI augmentation therapy (including Aralast and investigational Alpha1-PIs, by any route including intravenous and inhaled) within 42 days prior to first study product administration
  • The subject has received an investigational drug or device within 1 month prior to first study product administration, or the subject is currently receiving an investigational drug
  • The subject has a known selective immunoglobulin A (IgA) deficiency (IgA level < 15 mg/dL) and/or antibody to IgA
  • The subject has a pulmonary exacerbation or had a pulmonary exacerbation in the past 14 days prior to first study product administration
  • The subject is pregnant or lactating, or intends to become pregnant during the course of the study
  • The subject has a clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect subject safety or compliance

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ARALAST Fr. IV-1
60 mg/kg
Subjects meeting the eligibility criteria were randomized to receive either single dose ARALAST alpha1-proteinase inhibitor 60 mg/kg or single-dose ARALAST alpha1-proteinase inhibitor Fr. IV-1 60 mg/kg at 0.2 mL/kg/min during the first treatment period with crossover to the alternate study product during the second treatment period, with a minimum of 7 days between the two treatment periods.
Active Comparator: ARALAST
60mg/kg
Subjects meeting the eligibility criteria were randomized to receive either single dose ARALAST alpha1-proteinase inhibitor 60 mg/kg or single-dose ARALAST alpha1-proteinase inhibitor Fr. IV-1 60 mg/kg at 0.2 mL/kg/min during the first treatment period with crossover to the alternate study product during the second treatment period, with a minimum of 7 days between the two treatment periods.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area Under the Curve/Dose
Time Frame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Area under the plasma alpha1-proteinase inhibitor (α1-PI) concentration versus time curve (AUC) calculated by linear trapezoidal method per dose.
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Area Under the Curve Per Dose
Time Frame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Total area under the α1-PI concentration vs. time curve from pharmacokinetic day 0 to time infinity (AUC 0-infinity) per dose
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Systemic Clearance (CL)
Time Frame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Computed as dose divided by AUC 0-infinity (AUC 0-infinity was calculated as the sum of AUC from time 0 to the time of last quantifiable concentration plus a tail area correction)
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Mean Residence Time (MRT)
Time Frame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Computed as total area under the moment curve (AUMC) divided by total AUC
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Apparent Volume of Distribution at Steady State
Time Frame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Computed as weight-adjusted CL * MRT
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Terminal Half-life
Time Frame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Computed from the terminal or disposition rate constant obtained from log_e -linear fitting using the least squares deviation to the last five quantifiable concentrations above pre-infusion level.
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Maximum Plasma Concentration (Cmax)
Time Frame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Maximum α1-PI concentration following infusion
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Time to Maximum α1-PI Concentration Post-infusion (Tmax)
Time Frame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Time to reach C-max. Tmax is the number of days from infusion to maximum concentration. Samples drawn at the end of infusion are considered to be time zero.
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Incremental Recovery
Time Frame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Computed from Cmax (mg/ml) divided by dose per kg body weight (mg/kg).
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Adverse Events (AEs)
Time Frame: Throughout study period (7 months)
Investigators assessed severity of AEs (occurring during or after infusions) based on: MILD: Transient discomfort, does not interfere in a significant manner with participant's normal functioning level; Resolves spontaneously or may require minimal therapeutic intervention MODERATE: AE produces limited impairment of function, can require therapeutic intervention; AE produces no sequelae; SEVERE: AE results in marked impairment of function, can lead to temporary inability to resume usual life pattern; AE produces sequelae, which require prolonged therapeutic intervention
Throughout study period (7 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 20, 2005

Primary Completion (Actual)

June 5, 2006

Study Completion (Actual)

June 5, 2006

Study Registration Dates

First Submitted

October 19, 2005

First Submitted That Met QC Criteria

October 19, 2005

First Posted (Estimate)

October 20, 2005

Study Record Updates

Last Update Posted (Actual)

May 13, 2021

Last Update Submitted That Met QC Criteria

April 17, 2021

Last Verified

April 1, 2021

More Information

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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