Alpha 1-Antitrypsin DeficiencyPhase 1NCT00242385
Pharmacokinetic Study of ARALAST (Human Alpha1- PI)
A Phase 1 study testing Dose of 60 mg/kg Fraction IV-1 Alpha1-Proteinase Inhibitor and Dose of 60 mg/kg alpha1-proteinase inhibitor in people with Alpha 1-Antitrypsin Deficiency, run by Baxalta now part of Shire at 7 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Alpha 1-Antitrypsin Deficiency
- What is being tested?
- Dose of 60 mg/kg Fraction IV-1 Alpha1-Proteinase Inhibitor and Dose of 60 mg/kg alpha1-proteinase inhibitor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 20 Dec 2005to 5 Jun 2006
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 15Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
Australia4 sites
Study site
Adelaide, South Australia
Study site
Fitzroy, Victoria
Study site
Nedlands, Western Australia
Study site
Woodville, South Australia
New Zealand3 sites
Study site
Christchurch
Study site
Hamilton
Study site
Otahuhu, Auckland
About this study
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
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
- Being tested
- Dose of 60 mg/kg Fraction IV-1 Alpha1-Proteinase Inhibitor, Dose of 60 mg/kg alpha1-proteinase inhibitor
- Keywords
- Severe congenital Alpha1-Proteinase Inhibitor (Alpha1-PI) deficiency
- Medical subject headings
- alpha 1-Antitrypsin Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dose of 60 mg/kg Fraction IV-1 Alpha1-Proteinase InhibitorBiological
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.
Dose of 60 mg/kg alpha1-proteinase inhibitorBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| ARALAST Fr. IV-1 | Experimental | 60 mg/kg Receives: Biological: Dose of 60 mg/kg Fraction IV-1 Alpha1-Proteinase Inhibitor |
| ARALAST | Active comparator | 60mg/kg Receives: Biological: Dose of 60 mg/kg alpha1-proteinase inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Curve/Dose
Area under the plasma alpha1-proteinase inhibitor (α1-PI) concentration versus time curve (AUC) calculated by linear trapezoidal method per dose.
Measured: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Secondary outcomes (9)
Total Area Under the Curve Per Dose
Total area under the α1-PI concentration vs. time curve from pharmacokinetic day 0 to time infinity (AUC 0-infinity) per dose
Measured: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Systemic Clearance (CL)
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)
Measured: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Mean Residence Time (MRT)
Computed as total area under the moment curve (AUMC) divided by total AUC
Measured: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Apparent Volume of Distribution at Steady State
Computed as weight-adjusted CL * MRT
Measured: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Terminal Half-life
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.
Measured: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Maximum Plasma Concentration (Cmax)
Maximum α1-PI concentration following infusion
Measured: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Time to Maximum α1-PI Concentration Post-infusion (Tmax)
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.
Measured: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Incremental Recovery
Computed from Cmax (mg/ml) divided by dose per kg body weight (mg/kg).
Measured: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Adverse Events (AEs)
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
Measured: Throughout study period (7 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2005 (estimated)
- Study start20 Dec 2005
- Primary completion5 Jun 2006
- Study completion5 Jun 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alpha 1-Antitrypsin DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baxalta now part of Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Baxter Healthcare, Ltd. (New Zealand), Baxter Healthcare Pty. Ltd. (Australia)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00242385
- Sponsor's protocol ID
- 460501
- Status last verified
- Apr 2021
- First submitted
- 19 Oct 2005
- Last updated
- 13 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 36001294
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00242385
- Acronym / sponsor ID
- 460501
- Conditions
- Alpha 1-Antitrypsin Deficiency
- Keywords
- Severe congenital Alpha1-Proteinase Inhibitor (Alpha1-PI) deficiency
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Baxalta now part of ShireIndustry (pharma, biotech, devices)
- Collaborators
- Baxter Healthcare, Ltd. (New Zealand), Baxter Healthcare Pty. Ltd. (Australia)
- Study start
- 20 Dec 2005 (actual)
- Primary completion
- 5 Jun 2006 (actual)
- Study completion
- 5 Jun 2006 (actual)
- First posted
- 20 Oct 2005 (estimated)
- Results
- Posted 20 Jul 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ARALAST Fr. IV-1 | Experimental | Biological: Dose of 60 mg/kg Fraction IV-1 Alpha1-Proteinase Inhibitor60 mg/kg |
| ARALAST | Active comparator | Biological: Dose of 60 mg/kg alpha1-proteinase inhibitor60mg/kg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dose of 60 mg/kg Fraction IV-1 Alpha1-Proteinase InhibitorSubjects 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. | Biological | ARALAST Fr. IV-1 |
| Dose of 60 mg/kg alpha1-proteinase inhibitorSubjects 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. | Biological | ARALAST |
Primary outcome
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.
9 secondary outcomes
Total Area Under the Curve Per Dose
Time frame: 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
Mean Residence Time (MRT)
Time frame: 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
Terminal Half-life
Time frame: 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
Time to Maximum α1-PI Concentration Post-infusion (Tmax)
Time frame: 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
Adverse Events (AEs)
Time frame: Throughout study period (7 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36001294Li 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dose of 60 mg/kg Fraction IV-1 Alpha1-Proteinase Inhibitor and Dose of 60 mg/kg alpha1-proteinase inhibitor in people with Alpha 1-Antitrypsin Deficiency, run by Baxalta now part of Shire at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Australia, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jul 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Curve/Dose (time frame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00242385, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2021.