Clinical trial NCT00242385: Pharmacokinetic Study of ARALAST (Human Alpha1- PI)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alpha 1-Antitrypsin Deficiency
Keywords: Severe congenital Alpha1-Proteinase Inhibitor (Alpha1-PI) deficiency
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Baxter Healthcare, Ltd. (New Zealand), Baxter Healthcare Pty. Ltd. (Australia)
First posted: 2005-10-20
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Curve/Dose
timeFrame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Secondary outcomes:
measure: Total Area Under the Curve Per Dose
timeFrame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
measure: Systemic Clearance (CL)
timeFrame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
measure: Mean Residence Time (MRT)
timeFrame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
measure: Apparent Volume of Distribution at Steady State
timeFrame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
measure: Terminal Half-life
timeFrame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
measure: Maximum Plasma Concentration (Cmax)
timeFrame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
measure: Time to Maximum α1-PI Concentration Post-infusion (Tmax)
timeFrame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
measure: Incremental Recovery
timeFrame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
measure: Adverse Events (AEs)
timeFrame: Throughout study period (7 months)
Other outcomes:
Locations:
city: Adelaide
country: Australia
state: South Australia
city: Woodville
country: Australia
state: South Australia
city: Fitzroy
country: Australia
state: Victoria
city: Nedlands
country: Australia
state: Western Australia
city: Otahuhu
country: New Zealand
state: Auckland
city: Christchurch
country: New Zealand
city: Hamilton
country: New Zealand
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Li Z, Franke RM, Morris DN, Yel L. Pharmacokinetics and Biochemical Efficacy of an alpha1-Proteinase Inhibitor (Aralast NP) in alpha1-Antitrypsin Deficiency: a Cross-Product Retrospective Comparability Analysis. Pulm Ther. 2022 Sep;8(3):311-326. doi: 10.1007/s41030-022-00199-4. Epub 2022 Aug 24.