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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT02722304
Registration number
NCT02722304
Ethics application status
Date submitted
23/03/2016
Date registered
30/03/2016
Titles & IDs
Public title
Stage 1 Study of ARALAST NP and GLASSIA in A1PI Deficiency
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Scientific title
A Stage 1, Prospective, Randomized, Placebo-Controlled, Double- Blind Study to Evaluate the Safety and Efficacy of Alpha1-Proteinase Inhibitor (A1PI) Augmentation Therapy in Subjects With A1PI Deficiency and Chronic Obstructive Pulmonary Disease (COPD)
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Secondary ID [1]
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460503
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease
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Alpha1-antitrypsin Deficiency
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Condition category
Condition code
Human Genetics and Inherited Disorders
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Other human genetics and inherited disorders
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Respiratory
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Other respiratory disorders / diseases
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Respiratory
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Chronic obstructive pulmonary disease
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Other - ARALAST NP 60 mg/kg
Treatment: Other - ARALAST NP 120 mg/kg
Treatment: Other - GLASSIA 60 mg/kg
Treatment: Other - GLASSIA 120 mg/kg
Treatment: Other - Human Albumin 2%
Experimental: ARALAST NP 60 mg/kg - 60 mg/kg body weight/week
Experimental: ARALAST NP 120 mg/kg - 120 mg/kg body weight/week
Experimental: GLASSIA 60 mg/kg - 60 mg/kg body weight/week
Experimental: GLASSIA 120 mg/kg - 120 mg/kg body weight/week
Placebo comparator: Placebo - Human Albumin 2%
Treatment: Other: ARALAST NP 60 mg/kg
ARALAST NP is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy
Treatment: Other: ARALAST NP 120 mg/kg
ARALAST NP is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy
Treatment: Other: GLASSIA 60 mg/kg
GLASSIA is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy
Treatment: Other: GLASSIA 120 mg/kg
GLASSIA is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy
Treatment: Other: Human Albumin 2%
Human albumin 2% (by appropriate dilution with normal saline solution)
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Intervention code [1]
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Treatment: Other
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Rate of Change in Lung Density Based on Group 1 (ARALAST NP) Versus Placebo, Group 3 and Group 4 (GLASSIA) Versus Placebo
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Assessment method [1]
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Rate of change in lung density was assessed by computed tomography (CT) densitometry. Computed Tomography (CT) scans was used to measure lung density as a quantitative assessment of emphysema progression and treatment efficacy at each of the study visits. CT lung density at the 15th percentile (PD15) is the threshold below which 15% of the voxels have lower densities, and was used as the parameter for estimating the rate of lung density decline. Rate of change in lung density based on Group 1 (ARALAST NP) versus Placebo, Group 3 and Group 4 (GLASSIA) versus Placebo were reported. The safety analysis set used for all the efficacy parameter assessment.
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Timepoint [1]
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Baseline, Early termination of the study (approximately 22 months)
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Secondary outcome [1]
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Rate of Change in Lung Density for Each Treatment Group
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Assessment method [1]
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Rate of change in lung density was assessed by computed tomography (CT) densitometry for each treatment group. Computed Tomography (CT) scans was used to measure lung density as a quantitative assessment of emphysema progression and treatment efficacy at each of the study visits. The safety analysis set used for all the efficacy parameter assessment.
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Timepoint [1]
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Baseline, Early termination of the study (approximately 22 months)
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Secondary outcome [2]
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Mean Steady State Trough Concentration of Antigenic and Functional Alpha1-Proteinase Inhibitor (A1PI) for ARALAST NP and GLASSIA at Each Dose Level
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Assessment method [2]
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Mean steady state trough concentration of antigenic and functional alpha1-proteinase inhibitor (a1pi) for ARALAST NP and GLASSIA at each dose level was reported.
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Timepoint [2]
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Baseline, Early termination of the study (approximately 22 months)
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Secondary outcome [3]
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Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE)
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Assessment method [3]
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An Adverse event (AE) was defined as any untoward medical occurrence in a participant administered an IP that does not necessarily have a causal relationship with the treatment. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as AEs with a start date on or after the first dose of double-blind investigational product or a start date before the date of the first dose of double-blind investigational product that increased in severity or after the date of the first dose. TEAE related to Investigational Product (IP) and Study Procedures (SP) were considered. A non-serious AE is an AE that does not meet the criteria of an SAE. Number of events with related and unrelated serious and non-serious TEAE were reported.
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Timepoint [3]
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From start of study treatment up to early termination of the study (approximately 22 months)
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Secondary outcome [4]
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Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's)
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Assessment method [4]
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An Adverse event (AE) was defined as any untoward medical occurrence in a participant administered an IP that does not necessarily have a causal relationship with the treatment. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as AEs with a start date on or after the first dose of double-blind investigational product or a start date before the date of the first dose of double-blind investigational product that increased in severity or after the date of the first dose. A non-serious AE is an AE that does not meet the criteria of an SAE. TEAE related to IP and Study Procedures were considered. Percentage of participants with related and unrelated serious and non-serious TEAE were reported.
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Timepoint [4]
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From start of study treatment up to early termination of the study (approximately 22 months)
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Secondary outcome [5]
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Number of Events With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs)
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Assessment method [5]
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An Adverse event (AE) was defined as any untoward medical occurrence in a participant administered an IP that does not necessarily have a causal relationship with the treatment. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as AEs with a start date on or after the first dose of double-blind investigational product or a start date before the date of the first dose of double-blind investigational product that increased in severity or after the date of the first dose. A non-serious AE is an AE that does not meet the criteria of an SAE. TEAEs were temporally related to treatment administration (ie, occurred within 72 hours following the end of the infusion). TEAE Related to IP were considered.
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Timepoint [5]
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From start of study treatment up to early termination of the study (approximately 22 months)
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Secondary outcome [6]
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Percentage of Participants With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs)
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Assessment method [6]
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An Adverse event (AE) was defined as any untoward medical occurrence in a participant administered an IP that does not necessarily have a causal relationship with the treatment. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as AEs with a start date on or after the first dose of double-blind investigational product or a start date before the date of the first dose of double-blind investigational product that increased in severity or after the date of the first dose. A non-serious AE is an AE that does not meet the criteria of an SAE. TEAEs were temporally related to treatment administration (ie, occurred within 72 hours following the end of the infusion). TEAE Related to IP were considered.
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Timepoint [6]
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From start of study treatment up to early termination of the study (approximately 22 months)
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Secondary outcome [7]
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Number of Events With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs)
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Assessment method [7]
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An Adverse Reactions (ARs) plus suspected adverse reaction is any adverse event which met any of the following criteria: an adverse event that began during infusion or within 72 hours following the end of IP infusion; an adverse event considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration; an adverse event for which causality assessment was missing or indeterminate. Adverse reaction included both serious and non-serious ARs.
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Timepoint [7]
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From start of study treatment up to early termination of the study (approximately 22 months)
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Secondary outcome [8]
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Percentage of Participants With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs)
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Assessment method [8]
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An Adverse Reactions (AR) plus suspected adverse reaction is any adverse event which met any of the following criteria: an adverse event that began during infusion or within 72 hours following the end of IP infusion; an adverse event considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration; an adverse event for which causality assessment was missing or indeterminate. Adverse reaction included both serious and non-serious ARs.
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Timepoint [8]
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From start of study treatment up to early termination of the study (approximately 22 months)
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Secondary outcome [9]
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Percentage of Participants With at Least One Infusion Rate Change or Infusion Interruption or Stopped Due to AEs
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Assessment method [9]
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An Adverse event (AE) was defined as any untoward medical occurrence in a participant administered an IP that does not necessarily have a causal relationship with the treatment. Number of infusions for which the infusion rate was reduced and/or the infusion interrupted or stopped due to adverse events (AEs) were reported.
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Timepoint [9]
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From start of study treatment up to early termination of the study (approximately 22 months)
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Secondary outcome [10]
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Number of Participants Who Developed Anti-A1PI Antibodies Following Treatment With ARALAST NP or GLASSIA
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Assessment method [10]
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Number of participants who developed anti- A1PI antibodies following treatment with ARALAST NP or GLASSIA were reported. Anti-A1PI binding antibody were determined for the samples that tested positive or negative at each assessment time point.
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Timepoint [10]
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Baseline, Early termination of the study (approximately 22 months)
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Eligibility
Key inclusion criteria
1. =18 years of age at the time of screening
2. Endogenous plasma Alpha1-Proteinase Inhibitor (A1PI) level <8 µM at any time during the Screening period for treatment-naïve participants, or following 4-weeks minimum wash-out from previous augmentation therapy in treatment-experienced participants. The screening plasma A1PI level may be repeated if a participant obtains an exclusionary value that is suspected to be due to inadequate washout of A1PI).
3. Participant has documented A1PI genotype of Pi*Z/Z, Pi*Z/Null, Pi*Malton/Z, Pi*Null/Null, or other rare genotypes (except PI*MS, PI*MZ, or PI*SZ).
4. Clinically evident mild-moderate chronic obstructive pulmonary disease (COPD) (according to GOLD criteria for diagnosis) at the time of screening.
5. If the participant is treated with any respiratory medications including inhaled bronchodilators, inhaled corticosteroids, or systemic corticosteroids (e.g. prednisone = 10 mg/day or its equivalent), the doses of the participant's medications have remained stable for at least 28 days prior to screening.
6. No clinically significant abnormalities (other than emphysema, bronchitis or bronchiectasis) detected via a chest computed tomography (CT) or chest X-ray at the time of screening.
7. If female of childbearing potential, participant must have a negative pregnancy test at screening and agree to employ adequate birth control measures for the duration of the study.
8. Participant is willing and able to comply with the requirements of the protocol.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
1. Known ongoing or history of clinically significant pulmonary impairment other than emphysema/ COPD.
2. The participant is experiencing lower respiratory infection (LRTI)/acute pulmonary exacerbation (APE) at the time of enrollment (signing Informed consent form (ICF)). Participant may be rescreened after both clinical resolution of LRTI/APE and having also remained stable for at least 4 weeks after the end of LRTI/APE).
3. Known ongoing or history of cor pulmonale.
4. Known resting partial pressure of carbon dioxide (PaCO2) levels of > 45 mmHg.
5. Clinically significant congestive heart failure with New York Heart Association (NYHA) Class III/IV symptoms.
6. The participant has received an organ transplant, has undergone major lung surgery, or is currently on a transplant list.
7. Known history of ongoing malignancy (other than adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix).
8. Smoker or participant that has ceased smoking for less than one year prior to screening whose levels of cotinine are outside of the normal range of a nonsmoker.
All participants must agree to refrain from smoking throughout the course of the study.
9. The participant is receiving long-term therapy (> 28 days) of parenteral corticosteroids or oral corticosteroids at doses greater than 10 mg/day of prednisone or its equivalent).
10. The participant is receiving long-term round-the-clock oxygen supplementation (other than temporary for acute COPD exacerbation, or supplemental oxygen (O2) with continuous positive airway pressure [CPAP], or bi-level positive airway pressure [BiPAP] during the day).
11. Participant has contraindications for CT (e.g. body weight and/or body size exceeding the weight and gantry size limits specified by the manufacturer of the CT scanner, inability to lie flat in the CT scanner, claustrophobia, metal prosthesis or pacemaker in the chest wall or upper extremity that would impact lung density assessment).
12. Participant is unwilling or unable to modify bronchodilator medications for 6 hours for short acting ß2 agonists, 24 hours for long-acting ß2 agonists, and 48 hours for long acting anticholinergics prior to the scheduled quantitative CT scan.
13. Known severe immunoglobulin A (IgA) deficiency (ie, IgA level < 8 mg/dL at screening).
14. Known history of hypersensitivity following infusions of human blood or blood components (eg, human immunoglobulins or human albumin).
15. Presence of clinically significant laboratory abnormalities at the screening
16. The participant has a clinically significant medical, psychiatric, or cognitive illness, is a recreational drug/alcohol user, or has any other uncontrolled medical condition (eg, unstable angina, transient ischemic attack, uncontrolled hypertension) that, in the opinion of the investigator, would affect participant's safety or compliance or confound the results of the study.
17. Participant has been exposed to another IP within 28 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.
18. Participant is a family member or employee of the investigator.
19. If female, participant is pregnant or nursing at the time of enrollment.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Stopped early
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
2/11/2016
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
14/09/2018
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Sample size
Target
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Accrual to date
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Final
7
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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St Vincent's Hospital Melbourne - Fitzroy
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Recruitment postcode(s) [1]
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34741 - Fitzroy
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Arizona
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Country [2]
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United States of America
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State/province [2]
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California
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Country [3]
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United States of America
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State/province [3]
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Florida
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Country [4]
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United States of America
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State/province [4]
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Illinois
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Country [5]
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United States of America
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State/province [5]
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Indiana
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Country [6]
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United States of America
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State/province [6]
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New York
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Country [7]
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United States of America
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State/province [7]
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North Carolina
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Country [8]
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United States of America
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State/province [8]
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Texas
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Country [9]
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Canada
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State/province [9]
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Ontario
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Baxalta now part of Shire
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Address
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Country
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Other collaborator category [1]
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Commercial sector/industry
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Name [1]
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Baxalta Innovations GmbH, now part of Shire
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Address [1]
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Country [1]
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Ethics approval
Ethics application status
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Summary
Brief summary
The purpose of this study is to conduct a pilot study to evaluate the safety and efficacy of weekly administration of Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy in subjects with A1PI deficiency and emphysema/ chronic obstructive pulmonary disease (COPD).
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Trial website
https://clinicaltrials.gov/study/NCT02722304
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Study Director
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Address
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Takeda
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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No/undecided IPD sharing reason/comment
De-identified individual participant data from this particular study will not be shared as there is a reasonable likelihood that individual patients could be re-identified (due to the limited number of study participants).
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What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/04/NCT02722304/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/04/NCT02722304/SAP_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT02722304