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| Name | Class |
|---|---|
| Baxalta Innovations GmbH, now part of Shire | INDUSTRY |
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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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ARALAST NP 60 mg/kg | Experimental | 60 mg/kg body weight/week |
|
| ARALAST NP 120 mg/kg | Experimental | 120 mg/kg body weight/week |
|
| GLASSIA 60 mg/kg | Experimental | 60 mg/kg body weight/week |
|
| GLASSIA 120 mg/kg | Experimental | 120 mg/kg body weight/week |
|
| Placebo | Placebo Comparator | Human Albumin 2% |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ARALAST NP 60 mg/kg | Biological | ARALAST NP is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy |
|
| Measure | Description | Time Frame |
|---|---|---|
| Rate of Change in Lung Density Based on Group 1 (ARALAST NP) Versus Placebo, Group 3 and Group 4 (GLASSIA) Versus Placebo | 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. | Baseline, Early termination of the study (approximately 22 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of Change in Lung Density for Each Treatment Group | 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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Inclusion Criteria:
Exclusion Criteria:
Known ongoing or history of clinically significant pulmonary impairment other than emphysema/ COPD.
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).
Known ongoing or history of cor pulmonale.
Known resting partial pressure of carbon dioxide (PaCO2) levels of > 45 mmHg.
Clinically significant congestive heart failure with New York Heart Association (NYHA) Class III/IV symptoms.
The participant has received an organ transplant, has undergone major lung surgery, or is currently on a transplant list.
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).
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.
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).
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).
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).
Participant is unwilling or unable to modify bronchodilator medications for 6 hours for short acting β2 agonists, 24 hours for long-acting β2 agonists, and 48 hours for long acting anticholinergics prior to the scheduled quantitative CT scan.
Known severe immunoglobulin A (IgA) deficiency (ie, IgA level < 8 mg/dL at screening).
Known history of hypersensitivity following infusions of human blood or blood components (eg, human immunoglobulins or human albumin).
Presence of clinically significant laboratory abnormalities at the screening
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.
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.
Participant is a family member or employee of the investigator.
If female, participant is pregnant or nursing at the time of enrollment.
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Phoenix Medical Research Institute, LLC | Peoria | Arizona | 85381 | United States | ||
| Newport Native MD, Inc |
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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A total of 22 participants were screened for entry of study, of these, 15 participants were considered screen failures. Remaining 7 participants were enrolled and randomized in the study.
The study was conducted at 4 study centers in the United States (3) and Australia (1) between 02 November 2016 (first participant first visit) and 14 September 2018 (last participant last visit).
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| ID | Title | Description |
|---|---|---|
| FG000 | ARALAST NP 60 mg/kg (Group 1) | Participants received 60 milligram per kilogram body weight per week (mg/kg BW/week) of ARALAST NP intravenous (IV) infusion for a total of 96 weeks. |
| FG001 | ARALAST NP 120 mg/kg (Group 2) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 21, 2016 | Sep 18, 2019 |
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| ARALAST NP 120 mg/kg | Biological | ARALAST NP is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy |
|
|
| GLASSIA 60 mg/kg | Biological | GLASSIA is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy |
|
|
| GLASSIA 120 mg/kg | Biological | GLASSIA is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy |
|
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| Human Albumin 2% | Biological | Human albumin 2% (by appropriate dilution with normal saline solution) |
|
| Baseline, Early termination of the study (approximately 22 months) |
| Mean Steady State Trough Concentration of Antigenic and Functional Alpha1-Proteinase Inhibitor (A1PI) for ARALAST NP and GLASSIA at Each Dose Level | Mean steady state trough concentration of antigenic and functional alpha1-proteinase inhibitor (a1pi) for ARALAST NP and GLASSIA at each dose level was reported. | Baseline, Early termination of the study (approximately 22 months) |
| Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | 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. | From start of study treatment up to early termination of the study (approximately 22 months) |
| Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | 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. | From start of study treatment up to early termination of the study (approximately 22 months) |
| Number of Events With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs) | 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. | From start of study treatment up to early termination of the study (approximately 22 months) |
| Percentage of Participants With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs) | 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. | From start of study treatment up to early termination of the study (approximately 22 months) |
| Number of Events With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs) | 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. | From start of study treatment up to early termination of the study (approximately 22 months) |
| Percentage of Participants With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs) | 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. | From start of study treatment up to early termination of the study (approximately 22 months) |
| Percentage of Participants With at Least One Infusion Rate Change or Infusion Interruption or Stopped Due to AEs | 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. | From start of study treatment up to early termination of the study (approximately 22 months) |
| Number of Participants Who Developed Anti-A1PI Antibodies Following Treatment With ARALAST NP or GLASSIA | 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. | Baseline, Early termination of the study (approximately 22 months) |
| Newport Beach |
| California |
| 92663 |
| United States |
| Pulmonary Disease Specialists, P.A., / PDS Research | Kissimmee | Florida | 34741 | United States |
| L&C Professional Medical Research Institute | Miami | Florida | 33144 | United States |
| Loyola University Health System | Maywood | Illinois | 60153 | United States |
| Indiana University Health | Indianapolis | Indiana | 46202 | United States |
| La Porte County Institute for Clinical Research, Inc. | Michigan City | Indiana | 46360 | United States |
| Pulmonary Health Physicians | Fayetteville | New York | 13066 | United States |
| Clinical Research of Gastonia | Gastonia | North Carolina | 28054 | United States |
| Southeastern Research Center LLC | Winston-Salem | North Carolina | 27103 | United States |
| Metroplex Pulmonary and Sleep Center | Allen | Texas | 75013 | United States |
| Houston Pulmonary and Sleep Associates | Houston | Texas | 77065 | United States |
| Element Research Group | San Antonio | Texas | 78258 | United States |
| Renovatio Clinical-Respiratory & Sleep Disorders Specialists | The Woodlands | Texas | 77005 | United States |
| St Vincent's Hospital Melbourne | Fitzroy | Victoria | 34741 | Australia |
| LHSC - Victoria Hospital | London | Ontario | N6A 5W9 | Canada |
| Inspiration Research Limited | Toronto | Ontario | M5T 3A9 | Canada |
Participants received 120 mg/kg BW/week of ARALAST NP IV infusion for a total of 96 weeks.
| FG002 | GLASSIA 60 mg/kg (Group 3) | Participants received 60 mg/kg BW/week of GLASSIA IV infusion for a total of 96 weeks. |
| FG003 | GLASSIA 120 mg/kg (Group 4) | Participants received 120 mg/kg BW/week of GLASSIA IV infusion for a total of 96 weeks. |
| FG004 | Placebo (Group 5) | Participants received 6 milliliter per kilogram body weight per week (ml/kg BW/week) of placebo (human albumin two percent [%]) in normal saline for a total of 96 weeks. |
| Treated |
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| COMPLETED |
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| NOT COMPLETED |
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|
Safety Analysis Set (SAS) included all participants who had received any amount of investigational product (IP) or placebo, regardless of protocol deviations or non-adherence to the study procedures. Analysis was performed according to the treatment regimen received regardless of the randomized treatment regimen.
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| ID | Title | Description |
|---|---|---|
| BG000 | ARALAST NP 60 mg/kg (Group 1) | Participants received 60 milligram per kilogram body weight per week (mg/kg BW/week) of ARALAST NP intravenous (IV) infusion for a total of 96 weeks. |
| BG001 | ARALAST NP 120 mg/kg (Group 2) | Participants received 120 mg/kg BW/week of ARALAST NP IV infusion for a total of 96 weeks. |
| BG002 | GLASSIA 60 mg/kg (Group 3) | Participants received 60 mg/kg BW/week of GLASSIA IV infusion for a total of 96 weeks. |
| BG003 | GLASSIA 120 mg/kg (Group 4) | Participants received 120 mg/kg BW/week of GLASSIA IV infusion for a total of 96 weeks. |
| BG004 | Placebo (Group 5) | Participants received 6 milliliter per kilogram body weight per week (ml/kg BW/week) of placebo (human albumin two percent [%]) in normal saline for a total of 96 weeks. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Rate of Change in Lung Density Based on Group 1 (ARALAST NP) Versus Placebo, Group 3 and Group 4 (GLASSIA) Versus Placebo | 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. | Study was early terminated due to low and slow rate of enrollment, hence, data was not collected for this efficacy endpoint. | Posted | Baseline, Early termination of the study (approximately 22 months) |
|
| |||||||||||||||||||||||||
| Secondary | Rate of Change in Lung Density for Each Treatment Group | 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. | Study was early terminated due to low and slow rate of enrollment, hence, data was not collected for this efficacy endpoint. | Posted | Baseline, Early termination of the study (approximately 22 months) |
| ||||||||||||||||||||||||||
| Secondary | Mean Steady State Trough Concentration of Antigenic and Functional Alpha1-Proteinase Inhibitor (A1PI) for ARALAST NP and GLASSIA at Each Dose Level | Mean steady state trough concentration of antigenic and functional alpha1-proteinase inhibitor (a1pi) for ARALAST NP and GLASSIA at each dose level was reported. | Study was early terminated due to low and slow rate of enrollment, hence, data was not collected for this efficacy endpoint. | Posted | Baseline, Early termination of the study (approximately 22 months) |
| ||||||||||||||||||||||||||
| Secondary | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | 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. | SAS included all participants who had received any amount of IP or placebo, regardless of protocol deviations or non-adherence to the study procedures. Analysis was performed according to the treatment regimen received regardless of the randomized treatment regimen. | Posted | Number | Events | From start of study treatment up to early termination of the study (approximately 22 months) |
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| Secondary | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | 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. | SAS included all participants who had received any amount of IP or placebo, regardless of protocol deviations or non-adherence to the study procedures. Analysis was performed according to the treatment regimen received regardless of the randomized treatment regimen. | Posted | Number | Percentage of Participants | From start of study treatment up to early termination of the study (approximately 22 months) |
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| Secondary | Number of Events With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs) | 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. | SAS included all participants who had received any amount of IP or placebo, regardless of protocol deviations or non-adherence to the study procedures. Analysis was performed according to the treatment regimen received regardless of the ( randomized treatment regimen. | Posted | Number | Events | From start of study treatment up to early termination of the study (approximately 22 months) |
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| Secondary | Percentage of Participants With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs) | 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. | SAS included all participants who had received any amount of IP or placebo, regardless of protocol deviations or non-adherence to the study procedures. Analysis was performed according to the treatment regimen received regardless of the randomized treatment regimen. | Posted | Number | Percentage of Participants | From start of study treatment up to early termination of the study (approximately 22 months) |
| ||||||||||||||||||||||||
| Secondary | Number of Events With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs) | 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. | SAS included all participants who had received any amount of investigational product (IP) or placebo, regardless of protocol deviations or non-adherence to the study procedures. Analysis was performed according to the treatment regimen received regardless of the randomized treatment regimen. | Posted | Number | Events | From start of study treatment up to early termination of the study (approximately 22 months) |
| ||||||||||||||||||||||||
| Secondary | Percentage of Participants With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs) | 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. | SAS included all participants who had received any amount of IP or placebo, regardless of protocol deviations or non-adherence to the study procedures. Analysis was performed according to the treatment regimen received regardless of the randomized treatment regimen. | Posted | Number | Percentage of Participants | From start of study treatment up to early termination of the study (approximately 22 months) |
| ||||||||||||||||||||||||
| Secondary | Percentage of Participants With at Least One Infusion Rate Change or Infusion Interruption or Stopped Due to AEs | 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. | SAS included all participants who had received any amount of IP or placebo, regardless of protocol deviations or non-adherence to the study procedures. Analysis was performed according to the treatment regimen received regardless of the randomized treatment regimen. | Posted | Number | Percentage of Participants | From start of study treatment up to early termination of the study (approximately 22 months) |
| ||||||||||||||||||||||||
| Secondary | Number of Participants Who Developed Anti-A1PI Antibodies Following Treatment With ARALAST NP or GLASSIA | 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. | SAS included all participants who had received any amount of IP or placebo, regardless of protocol deviations or non-adherence to the study procedures. Analysis was performed according to the treatment regimen received regardless of the randomized treatment regimen. | Posted | Count of Participants | Participants | Baseline, Early termination of the study (approximately 22 months) |
|
From start of study treatment up to early termination of the study (approximately 22 months)
Study was terminated early. One arm/ group (ARALAST NP 120 mg/kg (Group 2)) did not have any participants randomized to it at the time of the study termination. Therefore there are zero participants at risk. This applies to the following fields, below for the ARALAST NP 120 mg/kg (Group 2) arm/group: - participants at risk for Serious Adverse Events - participants at risk for All-Cause Mortality - participants at risk for Other (Not Including Serious) Adverse Events
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ARALAST NP 60 mg/kg (Group 1) | Participants received 60 milligram per kilogram body weight per week (mg/kg BW/week) of ARALAST NP intravenous (IV) infusion for a total of 96 weeks. | 0 | 1 | 0 | 1 | 1 | 1 |
| EG001 | ARALAST NP 120 mg/kg (Group 2) | Participants received 120 mg/kg BW/week of ARALAST NP IV infusion for a total of 96 weeks. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG002 | GLASSIA 60 mg/kg (Group 3) | Participants received 60 mg/kg BW/week of GLASSIA IV infusion for a total of 96 weeks. | 0 | 1 | 0 | 1 | 0 | 1 |
| EG003 | GLASSIA 120 mg/kg (Group 4) | Participants received 120 mg/kg BW/week of GLASSIA IV infusion for a total of 96 weeks. | 0 | 1 | 0 | 1 | 0 | 1 |
| EG004 | Placebo (Group 5) | Participants received 6 milliliter per kilogram body weight per week (ml/kg BW/week) of placebo (human albumin two percent [%]) in normal saline for a total of 96 weeks. | 0 | 2 | 0 | 2 | 2 | 2 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Right Eye Retinal Detachment | Eye disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Nausea | Nervous system disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| CONTACT DERMATITIS | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| site conditions/ Catheter site rash/ MILD RASH AT THE SITE OF TAPE USED AT IV CANNULA SITE | General disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Vaginal haemorrhage/ PER VAGINAL BLEEDING | Reproductive system and breast disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Chronic obstructive pulmonary disease/ COPD EXACERBATION | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| DIARRHOEA | Gastrointestinal disorders | MedDRA 21.0 | Non-systematic Assessment |
|
The Data Monitoring Committee (DMC) reviewed the available efficacy and safety data and unanimously recommended to terminate the study. The decision was based on the very low number of enrollees, and the slow rate of participant enrollment.
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 19, 2019 | Sep 18, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| D019896 | alpha 1-Antitrypsin Deficiency |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D013352 | Subcutaneous Emphysema |
| D004646 | Emphysema |
Not provided
Not provided
| ID | Term |
|---|---|
| D000515 | alpha 1-Antitrypsin |
| ID | Term |
|---|---|
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D015843 | Serpins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000209 | Acute-Phase Proteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000510 | Alpha-Globulins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Placebo (Group 5) |
Participants received 6 milliliter per kilogram body weight per week (ml/kg BW/week) of placebo (human albumin two percent [%]) in normal saline for a total of 96 weeks. |
|
Participants received 6 milliliter per kilogram body weight per week (ml/kg BW/week) of placebo (human albumin two percent [%]) in normal saline for a total of 96 weeks.
|
| OG001 | GLASSIA 60 mg/kg (Group 3) | Participants received 60 mg/kg BW/week of GLASSIA IV infusion for a total of 96 weeks. |
| OG002 | GLASSIA 120 mg/kg (Group 4) | Participants received 120 mg/kg BW/week of GLASSIA IV infusion for a total of 96 weeks. |
| OG003 | Placebo (Group 5) | Participants received 6 milliliter per kilogram body weight per week (ml/kg BW/week) of placebo (human albumin two percent [%]) in normal saline for a total of 96 weeks. |
|
|
| OG001 | GLASSIA 60 mg/kg (Group 3) | Participants received 60 mg/kg BW/week of GLASSIA IV infusion for a total of 96 weeks. |
| OG002 | GLASSIA 120 mg/kg (Group 4) | Participants received 120 mg/kg BW/week of GLASSIA IV infusion for a total of 96 weeks. |
| OG003 | Placebo (Group 5) | Participants received 6 milliliter per kilogram body weight per week (ml/kg BW/week) of placebo (human albumin two percent [%]) in normal saline for a total of 96 weeks. |
|
|
| OG001 | GLASSIA 60 mg/kg (Group 3) | Participants received 60 mg/kg BW/week of GLASSIA IV infusion for a total of 96 weeks. |
| OG002 | GLASSIA 120 mg/kg (Group 4) | Participants received 120 mg/kg BW/week of GLASSIA IV infusion for a total of 96 weeks. |
| OG003 | Placebo (Group 5) | Participants received 6 milliliter per kilogram body weight per week (ml/kg BW/week) of placebo (human albumin two percent [%]) in normal saline for a total of 96 weeks. |
|
|
| OG001 | GLASSIA 60 mg/kg (Group 3) | Participants received 60 mg/kg BW/week of GLASSIA IV infusion for a total of 96 weeks. |
| OG002 | GLASSIA 120 mg/kg (Group 4) | Participants received 120 mg/kg BW/week of GLASSIA IV infusion for a total of 96 weeks. |
| OG003 | Placebo (Group 5) | Participants received 6 milliliter per kilogram body weight per week (ml/kg BW/week) of placebo (human albumin two percent [%]) in normal saline for a total of 96 weeks. |
|
|
| GLASSIA 120 mg/kg (Group 4) |
Participants received 120 mg/kg BW/week of GLASSIA IV infusion for a total of 96 weeks. |
| OG003 | Placebo (Group 5) | Participants received 6 milliliter per kilogram body weight per week (ml/kg BW/week) of placebo (human albumin two percent [%]) in normal saline for a total of 96 weeks. |
|
|
| GLASSIA 120 mg/kg (Group 4) |
Participants received 120 mg/kg BW/week of GLASSIA IV infusion for a total of 96 weeks. |
| OG003 | Placebo (Group 5) | Participants received 6 milliliter per kilogram body weight per week (ml/kg BW/week) of placebo (human albumin two percent [%]) in normal saline for a total of 96 weeks. |
|
|
Participants received 120 mg/kg BW/week of GLASSIA IV infusion for a total of 96 weeks.
| OG003 | Placebo (Group 5) | Participants received 6 milliliter per kilogram body weight per week (ml/kg BW/week) of placebo (human albumin two percent [%]) in normal saline for a total of 96 weeks. |
|
|
| OG003 | Placebo (Group 5) | Participants received 6 milliliter per kilogram body weight per week (ml/kg BW/week) of placebo (human albumin two percent [%]) in normal saline for a total of 96 weeks. |
|
|