Alpha 1-Antitrypsin DeficiencyPhase 4NCT00396006
Efficacy and Safety Study of Augmentation Therapy With ARALAST Fraction IV-1 (Human Alpha 1 - Proteinase Inhibitor)
A Phase 4 study testing Alpha1-Proteinase Inhibitor in people with Alpha 1-Antitrypsin Deficiency, run by Baxalta now part of Shire at 5 sites in 2 countries.
Trial summary
The purpose of this study is to evaluate the effects of weekly augmentation therapy with ARALAST Fraction IV-1 (Fr IV-1) on epithelial lining fluid (ELF) alpha 1-proteinase inhibitor levels and other ELF analytes and to assess the safety of the treatment. 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?
- Alpha1-Proteinase Inhibitor
- Type of treatment
- Injection or infusion
- How many people
- 21 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 27 Oct 2006to 14 Dec 2007
- Phase
- Phase 4
- 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
- Signed and dated informed consent.
- Male or female 18 years of age or older.
- Documented, endogenous serum α1-PI level < 40 mg/dL measured at screening (unless otherwise approved by the Sponsor) after a minimum of 28-day washout of any prior replacement therapy (if applicable).
- Phenotype Pi Z (which includes Pi*Z/Z, Pi*Z/Null, or Pi*Malton/Z), or Pi*Null/Null.
- Pulmonary functions at screening meeting the following criteria:
- Forced expiratory volume at 1 second (FEV1) >= 50% of predicted value; or
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- FEV1 > 35% of predicted value and diffusing capacity for carbon monoxide > 45% of predicated value, with no supplemental oxygen therapy and < 3 pulmonary exacerbations or bronchitis requiring antibiotics/corticosteroids within the past 12 months).
- For any female of childbearing potential, a negative urine test for pregnancy within 7 days prior to the first bronchoalveolar lavage (BAL) visit and agreement to employ adequate birth control measures for the duration of the study.
- No clinically significant abnormalities detected on a 12-lead electrocardiogram (ECG) performed at the screening visit (ECG previously obtained within the past 12 months may be used, if available).
- Laboratory results obtained at the screening visit, meeting the following criteria:
- Serum alanine aminotransferase (ALT) <= 2 times upper limit of normal (ULN)
- Serum aspartate aminotransferase (AST) <= 2 times 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 (Hgb) >= 10.0 g/dL
- Platelet count >= 105/mm3
- If the subject is treated with respiratory medications, such as inhaled bronchodilators or inhaled corticosteroids, or other chronic medications for the treatment of the subjects´s other medical condition(s), the subject's medication doses were unchanged for at least 14 days prior to the baseline BAL visit.
Who cannot join
- Clinically significant pulmonary impairment, other than chronic pulmonary disease (COPD).
- The subject has received any alpha 1 proteinase inhibitor (α1-PI) augmentation therapy (e.g., Prolastin, Zemaira, Aralast, or an investigational α1-PI, by any route including intravenous and inhaled) within 28 days prior to screening.
- The subject has received an investigational drug or device within 1 month prior to screening, or the subject is currently receiving an investigational drug or device. If the subject receives another investigational drug or device after enrollment, the subjects is to be withdrawn from the trial.
- Presence of clinical symptoms of any lower respiratory tract infection or acute pulmonary exacerbation within 14 days prior to screening.
- The subject has a known selective Immunoglobulin A (IgA) deficiency (IgA level less than 15 mg/dL) and/or antibody against IgA.
- The subject is pregnant or lactating, or intends to become pregnant during the course of the study.
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- The subject is not a suitable candidate for a BAL procedure.
- Moderate or severe bronchiectasis (total daily sputum production > 10 mL).
- 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.
- Prior history of adverse reaction to local anaesthetics, sedatives, pain control drugs, and other medication employed at the study center for perioperative care associated with the BAL procedure.
- Long-term use of oral or parenteral glucocorticosteroid within 28 days prior to screening.
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
Australia3 sites
Study site
Adelaide, South Australia
Study site
Melbourne, Victoria
Study site
Nedlands, Western Australia
About this study
Official title: The Effect of Augmentation Therapy With ARALAST Fraction IV-1 (ARALAST) Alpha1-Proteinase Inhibitor (α1-PI) on the Level of α1-PI and Other Analytes in the Bronchoalveolar (BAL) Epithelial Lining Fluid (ELF)
The purpose of this study is to evaluate the effects of weekly augmentation therapy with ARALAST Fraction IV-1 (Fr IV-1) on epithelial lining fluid (ELF) alpha 1-proteinase inhibitor levels and other ELF analytes and to assess the safety of the treatment. Eligible subjects with a diagnosis of severe congenital alpha 1-antitrypsin deficiency will receive 8 consecutive weekly treatments with 60 mg/kg/week of functional ARALAST Fr IV-1 administered intravenously. The efficacy and safety assessments will include two bronchoscopies with bronchoalveolar lavage on study initiation and on study termination and multiple imaging and laboratory safety assessments. Each subject will participate for a minimum of 12 weeks.
- Conditions
- Alpha 1-Antitrypsin Deficiency
- Being tested
- Alpha1-Proteinase Inhibitor
- 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.
Alpha1-Proteinase InhibitorBiological
Also called ARALAST Fr.IV-1, ARALAST NP
60 mg/kg, weekly, intravenous infusion
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Bronchoalveolar Lavage (BAL) Epithelial Lining Fluid (ELF) Alpha1-Proteinase Inhibitor (α1-PI) Level
Median change BAL ELF antigenic α1-PI level the from baseline to post-treatment
Measured: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks)
The Number of Adverse Events (AEs) Related to the Infusion of ARALAST Fr. IV 1 Administered at a Rate of 0.2 mL/kg/Min
Measured: During 8 consecutive weeks of treatment
Number of Changes in the Rate of Infusion
Number of decreases in the rate or discontinuations of infusion at 0.2 mL/kg/min
Measured: During 8 consecutive weeks of treatment
Secondary outcomes (5)
Ratio of Post- to Pre-treatment BAL ELF Antineutrophil Elastase Capacity (ANEC) Levels
Median ratio of post- to pre-treatment BAL ELF ANEC levels
Measured: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks)
Change in in the Ratio of BAL ELF α1-PI to Human Neutrophil Elastase (HNE) Complex Concentration
Median change in the ratio of BAL ELF α1-PI to HNE complex concentration from baseline to post-treatment
Measured: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks)
Change in the α1-PI Plasma Level
Mean change in the plasma level of α1-PI from baseline to post-treatment
Measured: Blood samples were collected at baseline and after 8 consecutive weeks of treatment
Change in the Plasma Antineutrophil Elastase Capacity (ANEC) Level
Mean change in the plasma ANEC level from baseline to post-treatment
Measured: Blood samples were collected at baseline and after 8 consecutive weeks of treatment
Clinically Significant Changes in Vital Signs From Pre- to Post-Infusion
Clinically significant changes in vital signs from pre- to post-infusion are: • Heart rate: 25% increase above pre-infusion value • Blood pressure: ≥ 30 mm Hg change from pre-infusion blood pressure (systolic or diastolic) • Temperature: an increase in body temperature to >38°C (>100.4°F). If the pre-infusion body temperature was already >38°C (>100.4°F), then any further increase in body temperature by 1.1°C (1.98°F) or more was considered clinically significant. • Respiratory rate: 25% increase above pre-infusion value
Measured: During 8 consecutive weeks of infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2006 (estimated)
- Study start27 Oct 2006
- Primary completion14 Dec 2007
- Study completion14 Dec 2007
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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baxalta now part of Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00396006
- Sponsor's protocol ID
- 460502
- Status last verified
- Apr 2021
- First submitted
- 3 Nov 2006
- 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
- The Effect of Augmentation Therapy With ARALAST Fraction IV-1 (ARALAST) Alpha1-Proteinase Inhibitor (α1-PI) on the Level of α1-PI and Other Analytes in the Bronchoalveolar (BAL) Epithelial Lining Fluid (ELF)
- ClinicalTrials.gov ID
- NCT00396006
- Acronym / sponsor ID
- 460502
- Conditions
- Alpha 1-Antitrypsin Deficiency
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Baxalta now part of ShireIndustry (pharma, biotech, devices)
- Study start
- 27 Oct 2006 (actual)
- Primary completion
- 14 Dec 2007 (actual)
- Study completion
- 14 Dec 2007 (actual)
- First posted
- 6 Nov 2006 (estimated)
- Results
- Posted 4 Jan 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the effects of weekly augmentation therapy with ARALAST Fraction IV-1 (Fr IV-1) on epithelial lining fluid (ELF) alpha 1-proteinase inhibitor levels and other ELF analytes and to assess the safety of the treatment. Eligible subjects with a diagnosis of severe congenital alpha 1-antitrypsin deficiency will receive 8 consecutive weekly treatments with 60 mg/kg/week of functional ARALAST Fr IV-1 administered intravenously. The efficacy and safety assessments will include two bronchoscopies with bronchoalveolar lavage on study initiation and on study termination and multiple imaging and laboratory safety assessments. Each subject will participate for a minimum of 12 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Signed and dated informed consent.
- Male or female 18 years of age or older.
- Documented, endogenous serum α1-PI level < 40 mg/dL measured at screening (unless otherwise approved by the Sponsor) after a minimum of 28-day washout of any prior replacement therapy (if applicable).
- Phenotype Pi Z (which includes Pi*Z/Z, Pi*Z/Null, or Pi*Malton/Z), or Pi*Null/Null.
- Pulmonary functions at screening meeting the following criteria:
Key exclusion criteria (11 listed)
- Clinically significant pulmonary impairment, other than chronic pulmonary disease (COPD).
- The subject has received any alpha 1 proteinase inhibitor (α1-PI) augmentation therapy (e.g., Prolastin, Zemaira, Aralast, or an investigational α1-PI, by any route including intravenous and inhaled) within 28 days prior to screening.
- The subject has received an investigational drug or device within 1 month prior to screening, or the subject is currently receiving an investigational drug or device. If the subject receives another investigational drug or device after enrollment, the subjects is to be withdrawn from the trial.
- Presence of clinical symptoms of any lower respiratory tract infection or acute pulmonary exacerbation within 14 days prior to screening.
- The subject has a known selective Immunoglobulin A (IgA) deficiency (IgA level less than 15 mg/dL) and/or antibody against IgA.
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 |
|---|---|---|
| Alpha1-Proteinase InhibitorAlso: ARALAST Fr.IV-1, ARALAST NP60 mg/kg, weekly, intravenous infusion | Biological | – |
Primary outcome
Change in Bronchoalveolar Lavage (BAL) Epithelial Lining Fluid (ELF) Alpha1-Proteinase Inhibitor (α1-PI) Level
Time frame: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks)
Median change BAL ELF antigenic α1-PI level the from baseline to post-treatment
The Number of Adverse Events (AEs) Related to the Infusion of ARALAST Fr. IV 1 Administered at a Rate of 0.2 mL/kg/Min
Time frame: During 8 consecutive weeks of treatment
Number of Changes in the Rate of Infusion
Time frame: During 8 consecutive weeks of treatment
Number of decreases in the rate or discontinuations of infusion at 0.2 mL/kg/min
5 secondary outcomes
Ratio of Post- to Pre-treatment BAL ELF Antineutrophil Elastase Capacity (ANEC) Levels
Time frame: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks)
Change in in the Ratio of BAL ELF α1-PI to Human Neutrophil Elastase (HNE) Complex Concentration
Time frame: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks)
Change in the α1-PI Plasma Level
Time frame: Blood samples were collected at baseline and after 8 consecutive weeks of treatment
Change in the Plasma Antineutrophil Elastase Capacity (ANEC) Level
Time frame: Blood samples were collected at baseline and after 8 consecutive weeks of treatment
Clinically Significant Changes in Vital Signs From Pre- to Post-Infusion
Time frame: During 8 consecutive weeks of infusion
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
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Alpha1-Proteinase Inhibitor in people with Alpha 1-Antitrypsin Deficiency, run by Baxalta now part of Shire at 5 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 19 inclusion and 11 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 5 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 4 Jan 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?
Change in Bronchoalveolar Lavage (BAL) Epithelial Lining Fluid (ELF) Alpha1-Proteinase Inhibitor (α1-PI) Level (time frame: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks)). The study lists 3 primary outcomes in all. 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 NCT00396006, 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.