Pharmacokinetic Study of ARALAST (Human Alpha1- PI)

NCT ID: NCT00242385

Last Updated: 2021-05-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-20
• Study Completion Date: 2006-06-05

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.

Conditions

Alpha 1-Antitrypsin Deficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

ARALAST Fr. IV-1

60 mg/kg

Group Type: EXPERIMENTAL

Dose of 60 mg/kg Fraction IV-1 Alpha1-Proteinase Inhibitor

Intervention Type: BIOLOGICAL

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.

ARALAST

60mg/kg

Group Type: ACTIVE_COMPARATOR

Dose of 60 mg/kg alpha1-proteinase inhibitor

Intervention Type: BIOLOGICAL

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.

Interventions

Dose of 60 mg/kg Fraction IV-1 Alpha1-Proteinase Inhibitor

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.

Intervention Type: BIOLOGICAL

Dose of 60 mg/kg alpha1-proteinase inhibitor

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.

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baxter Healthcare, Ltd. (New Zealand), Baxter Healthcare Pty. Ltd. (Australia)

INDUSTRY

Sponsor Role: collaborator

Baxalta now part of Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Adelaide, South Australia, Australia

Woodville, South Australia, Australia

Fitzroy, Victoria, Australia

Nedlands, Western Australia, Australia

Otahuhu, Auckland, New Zealand

Christchurch, , New Zealand

Hamilton, , New Zealand

Countries

Australia; New Zealand

References

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.

Reference Type: DERIVED

PMID: 36001294 (View on PubMed)

Other Identifiers

460501

Identifier Type: -

Identifier Source: org_study_id