Alpha1-antitrypsin Deficiency, Chronic Obstructive Pulmonary Disease
Conditions
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).
Interventions
BIOLOGICALARALAST NP 60 mg/kg
ARALAST NP is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy
BIOLOGICALARALAST NP 120 mg/kg
ARALAST NP is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy
BIOLOGICALGLASSIA 60 mg/kg
GLASSIA is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy
BIOLOGICALGLASSIA 120 mg/kg
GLASSIA is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy
BIOLOGICALHuman Albumin 2%
Human albumin 2% (by appropriate dilution with normal saline solution)
Sponsors
Baxalta Innovations GmbH, now part of Shire
Baxalta now part of Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
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 β2 agonists, 24 hours for long-acting β2 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Change in Lung Density Based on Group 1 (ARALAST NP) Versus Placebo, Group 3 and Group 4 (GLASSIA) Versus Placebo | Baseline, Early termination of the study (approximately 22 months) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Steady State Trough Concentration of Antigenic and Functional Alpha1-Proteinase Inhibitor (A1PI) for ARALAST NP and GLASSIA at Each Dose Level | 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 was reported. |
| Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | From start of study treatment up to early termination of the study (approximately 22 months) | 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. |
| Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | From start of study treatment up to early termination of the study (approximately 22 months) | 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. |
| Number of Events With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs) | From start of study treatment up to early termination of the study (approximately 22 months) | 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. |
| Rate of Change in Lung Density for Each Treatment Group | Baseline, Early termination of the study (approximately 22 months) | 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. |
| Number of Events With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs) | From start of study treatment up to early termination of the study (approximately 22 months) | 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. |
| Percentage of Participants With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs) | From start of study treatment up to early termination of the study (approximately 22 months) | 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. |
| Percentage of Participants With at Least One Infusion Rate Change or Infusion Interruption or Stopped Due to AEs | From start of study treatment up to early termination of the study (approximately 22 months) | 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. |
| Number of Participants Who Developed Anti-A1PI Antibodies Following Treatment With ARALAST NP or GLASSIA | Baseline, Early termination of the study (approximately 22 months) | 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. |
| Percentage of Participants With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs) | From start of study treatment up to early termination of the study (approximately 22 months) | 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. |
Countries
Australia, Canada, United States
Participant flow
Recruitment details
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).
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 1 |
| 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 |
| GLASSIA 60 mg/kg (Group 3) Participants received 60 mg/kg BW/week of GLASSIA IV infusion for a total of 96 weeks. | 1 |
| GLASSIA 120 mg/kg (Group 4) Participants received 120 mg/kg BW/week of GLASSIA IV infusion for a total of 96 weeks. | 1 |
| 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. | 2 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Other | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Study Terminated by Sponsor | 1 | 0 | 2 | 1 | 1 |
Baseline characteristics
| Characteristic | ARALAST NP 60 mg/kg (Group 1) | GLASSIA 60 mg/kg (Group 3) | GLASSIA 120 mg/kg (Group 4) | Placebo (Group 5) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 62.0 Years | 65.0 Years | 68.0 Years | 46.0 Years STANDARD_DEVIATION 4.24 | 57.4 Years STANDARD_DEVIATION 10.83 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 0 | 0 / 1 | 0 / 1 | 0 / 2 |
| other Total, other adverse events | 1 / 1 | 0 / 0 | 0 / 1 | 0 / 1 | 2 / 2 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 | 0 / 1 | 0 / 1 | 0 / 2 |
Outcome results
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.
Time frame: Baseline, Early termination of the study (approximately 22 months)
Population: Study was early terminated due to low and slow rate of enrollment, hence, data was not collected for this efficacy endpoint.
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.
Time frame: Baseline, Early termination of the study (approximately 22 months)
Population: Study was early terminated due to low and slow rate of enrollment, hence, data was not collected for this efficacy endpoint.
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.
Time frame: From start of study treatment up to early termination of the study (approximately 22 months)
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ARALAST NP 60 mg/kg Versus Placebo | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Serious TEAE: Events Related to IP | 0 Events |
| ARALAST NP 60 mg/kg Versus Placebo | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Non-serious TEAE: Events Related to IP | 0 Events |
| ARALAST NP 60 mg/kg Versus Placebo | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Serious TEAE: Events Related to SP | 0 Events |
| ARALAST NP 60 mg/kg Versus Placebo | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Non-serious TEAE: Events Related to SP | 0 Events |
| ARALAST NP 60 mg/kg Versus Placebo | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Serious TEAE: Unrelated Events | 0 Events |
| ARALAST NP 60 mg/kg Versus Placebo | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Non-serious TEAE: Unrelated Events | 2 Events |
| GLASSIA 60 mg/kg Versus Placebo | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Non-serious TEAE: Unrelated Events | 0 Events |
| GLASSIA 60 mg/kg Versus Placebo | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Non-serious TEAE: Events Related to SP | 0 Events |
| GLASSIA 60 mg/kg Versus Placebo | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Serious TEAE: Events Related to IP | 0 Events |
| GLASSIA 60 mg/kg Versus Placebo | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Serious TEAE: Events Related to SP | 0 Events |
| GLASSIA 60 mg/kg Versus Placebo | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Non-serious TEAE: Events Related to IP | 0 Events |
| GLASSIA 60 mg/kg Versus Placebo | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Serious TEAE: Unrelated Events | 0 Events |
| GLASSIA 120 mg/kg Versus Placebo | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Non-serious TEAE: Events Related to IP | 0 Events |
| GLASSIA 120 mg/kg Versus Placebo | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Serious TEAE: Events Related to SP | 0 Events |
| GLASSIA 120 mg/kg Versus Placebo | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Non-serious TEAE: Events Related to SP | 0 Events |
| GLASSIA 120 mg/kg Versus Placebo | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Non-serious TEAE: Unrelated Events | 0 Events |
| GLASSIA 120 mg/kg Versus Placebo | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Serious TEAE: Unrelated Events | 0 Events |
| GLASSIA 120 mg/kg Versus Placebo | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Serious TEAE: Events Related to IP | 0 Events |
| Placebo (Group 5) | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Serious TEAE: Unrelated Events | 0 Events |
| Placebo (Group 5) | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Non-serious TEAE: Unrelated Events | 5 Events |
| Placebo (Group 5) | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Non-serious TEAE: Events Related to IP | 19 Events |
| Placebo (Group 5) | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Non-serious TEAE: Events Related to SP | 1 Events |
| Placebo (Group 5) | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Serious TEAE: Events Related to IP | 0 Events |
| Placebo (Group 5) | Number of Events With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Event (TEAE) | Serious TEAE: Events Related to SP | 0 Events |
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.
Time frame: From start of study treatment up to early termination of the study (approximately 22 months)
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ARALAST NP 60 mg/kg Versus Placebo | Number of Events With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs) | Suspected ARs or Non-serious ARs | 1 Events |
| ARALAST NP 60 mg/kg Versus Placebo | Number of Events With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs) | Suspected ARs or Serious ARs | 0 Events |
| GLASSIA 60 mg/kg Versus Placebo | Number of Events With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs) | Suspected ARs or Serious ARs | 0 Events |
| GLASSIA 60 mg/kg Versus Placebo | Number of Events With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs) | Suspected ARs or Non-serious ARs | 0 Events |
| GLASSIA 120 mg/kg Versus Placebo | Number of Events With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs) | Suspected ARs or Non-serious ARs | 0 Events |
| GLASSIA 120 mg/kg Versus Placebo | Number of Events With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs) | Suspected ARs or Serious ARs | 0 Events |
| Placebo (Group 5) | Number of Events With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs) | Suspected ARs or Non-serious ARs | 24 Events |
| Placebo (Group 5) | Number of Events With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs) | Suspected ARs or Serious ARs | 0 Events |
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.
Time frame: From start of study treatment up to early termination of the study (approximately 22 months)
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ARALAST NP 60 mg/kg Versus Placebo | Number of Events With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs) | Temporally Serious TEAE Related to IP | 0 Events |
| ARALAST NP 60 mg/kg Versus Placebo | Number of Events With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs) | Temporally Non-Serious TEAE Related to IP | 0 Events |
| GLASSIA 60 mg/kg Versus Placebo | Number of Events With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs) | Temporally Non-Serious TEAE Related to IP | 0 Events |
| GLASSIA 60 mg/kg Versus Placebo | Number of Events With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs) | Temporally Serious TEAE Related to IP | 0 Events |
| GLASSIA 120 mg/kg Versus Placebo | Number of Events With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs) | Temporally Serious TEAE Related to IP | 0 Events |
| GLASSIA 120 mg/kg Versus Placebo | Number of Events With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs) | Temporally Non-Serious TEAE Related to IP | 0 Events |
| Placebo (Group 5) | Number of Events With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs) | Temporally Serious TEAE Related to IP | 0 Events |
| Placebo (Group 5) | Number of Events With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs) | Temporally Non-Serious TEAE Related to IP | 17 Events |
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.
Time frame: Baseline, Early termination of the study (approximately 22 months)
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ARALAST NP 60 mg/kg Versus Placebo | Number of Participants Who Developed Anti-A1PI Antibodies Following Treatment With ARALAST NP or GLASSIA | 0 Participants |
| GLASSIA 60 mg/kg Versus Placebo | Number of Participants Who Developed Anti-A1PI Antibodies Following Treatment With ARALAST NP or GLASSIA | 0 Participants |
| GLASSIA 120 mg/kg Versus Placebo | Number of Participants Who Developed Anti-A1PI Antibodies Following Treatment With ARALAST NP or GLASSIA | 0 Participants |
| Placebo (Group 5) | Number of Participants Who Developed Anti-A1PI Antibodies Following Treatment With ARALAST NP or GLASSIA | 0 Participants |
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.
Time frame: From start of study treatment up to early termination of the study (approximately 22 months)
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ARALAST NP 60 mg/kg Versus Placebo | Percentage of Participants With at Least One Infusion Rate Change or Infusion Interruption or Stopped Due to AEs | Participants with at Least 1 Infusion Rate Change | 0 Percentage of Participants |
| ARALAST NP 60 mg/kg Versus Placebo | Percentage of Participants With at Least One Infusion Rate Change or Infusion Interruption or Stopped Due to AEs | Participantswith at Least 1 Infusion Interruption | 0 Percentage of Participants |
| GLASSIA 60 mg/kg Versus Placebo | Percentage of Participants With at Least One Infusion Rate Change or Infusion Interruption or Stopped Due to AEs | Participantswith at Least 1 Infusion Interruption | 0 Percentage of Participants |
| GLASSIA 60 mg/kg Versus Placebo | Percentage of Participants With at Least One Infusion Rate Change or Infusion Interruption or Stopped Due to AEs | Participants with at Least 1 Infusion Rate Change | 0 Percentage of Participants |
| GLASSIA 120 mg/kg Versus Placebo | Percentage of Participants With at Least One Infusion Rate Change or Infusion Interruption or Stopped Due to AEs | Participants with at Least 1 Infusion Rate Change | 0 Percentage of Participants |
| GLASSIA 120 mg/kg Versus Placebo | Percentage of Participants With at Least One Infusion Rate Change or Infusion Interruption or Stopped Due to AEs | Participantswith at Least 1 Infusion Interruption | 0 Percentage of Participants |
| Placebo (Group 5) | Percentage of Participants With at Least One Infusion Rate Change or Infusion Interruption or Stopped Due to AEs | Participants with at Least 1 Infusion Rate Change | 50 Percentage of Participants |
| Placebo (Group 5) | Percentage of Participants With at Least One Infusion Rate Change or Infusion Interruption or Stopped Due to AEs | Participantswith at Least 1 Infusion Interruption | 50 Percentage of Participants |
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.
Time frame: From start of study treatment up to early termination of the study (approximately 22 months)
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ARALAST NP 60 mg/kg Versus Placebo | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Serious TEAE: Related to IP | 0 Percentage of Participants |
| ARALAST NP 60 mg/kg Versus Placebo | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Non-Serious TEAE: Related to IP | 0 Percentage of Participants |
| ARALAST NP 60 mg/kg Versus Placebo | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Serious TEAE: Related to SP | 0 Percentage of Participants |
| ARALAST NP 60 mg/kg Versus Placebo | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Non-Serious TEAE: Related to SP | 0 Percentage of Participants |
| ARALAST NP 60 mg/kg Versus Placebo | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Serious TEAE: Unrelated | 0 Percentage of Participants |
| ARALAST NP 60 mg/kg Versus Placebo | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Non-Serious TEAE: Unrelated | 100 Percentage of Participants |
| GLASSIA 60 mg/kg Versus Placebo | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Non-Serious TEAE: Unrelated | 0 Percentage of Participants |
| GLASSIA 60 mg/kg Versus Placebo | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Non-Serious TEAE: Related to SP | 0 Percentage of Participants |
| GLASSIA 60 mg/kg Versus Placebo | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Serious TEAE: Related to IP | 0 Percentage of Participants |
| GLASSIA 60 mg/kg Versus Placebo | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Serious TEAE: Related to SP | 0 Percentage of Participants |
| GLASSIA 60 mg/kg Versus Placebo | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Non-Serious TEAE: Related to IP | 0 Percentage of Participants |
| GLASSIA 60 mg/kg Versus Placebo | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Serious TEAE: Unrelated | 0 Percentage of Participants |
| GLASSIA 120 mg/kg Versus Placebo | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Non-Serious TEAE: Related to IP | 0 Percentage of Participants |
| GLASSIA 120 mg/kg Versus Placebo | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Serious TEAE: Related to SP | 0 Percentage of Participants |
| GLASSIA 120 mg/kg Versus Placebo | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Non-Serious TEAE: Related to SP | 0 Percentage of Participants |
| GLASSIA 120 mg/kg Versus Placebo | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Non-Serious TEAE: Unrelated | 0 Percentage of Participants |
| GLASSIA 120 mg/kg Versus Placebo | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Serious TEAE: Unrelated | 0 Percentage of Participants |
| GLASSIA 120 mg/kg Versus Placebo | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Serious TEAE: Related to IP | 0 Percentage of Participants |
| Placebo (Group 5) | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Serious TEAE: Unrelated | 0 Percentage of Participants |
| Placebo (Group 5) | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Non-Serious TEAE: Unrelated | 100 Percentage of Participants |
| Placebo (Group 5) | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Non-Serious TEAE: Related to IP | 50 Percentage of Participants |
| Placebo (Group 5) | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Non-Serious TEAE: Related to SP | 50 Percentage of Participants |
| Placebo (Group 5) | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Serious TEAE: Related to IP | 0 Percentage of Participants |
| Placebo (Group 5) | Percentage of Participants With Related and Unrelated Serious and Non-Serious Treatment Emergent Adverse Events (TEAE's) | Serious TEAE: Related to SP | 0 Percentage of Participants |
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.
Time frame: From start of study treatment up to early termination of the study (approximately 22 months)
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ARALAST NP 60 mg/kg Versus Placebo | Percentage of Participants With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs) | Suspected ARs or Non-serious ARs | 100 Percentage of Participants |
| ARALAST NP 60 mg/kg Versus Placebo | Percentage of Participants With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs) | Suspected ARs or Serious ARs | 0 Percentage of Participants |
| GLASSIA 60 mg/kg Versus Placebo | Percentage of Participants With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs) | Suspected ARs or Serious ARs | 0 Percentage of Participants |
| GLASSIA 60 mg/kg Versus Placebo | Percentage of Participants With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs) | Suspected ARs or Non-serious ARs | 0 Percentage of Participants |
| GLASSIA 120 mg/kg Versus Placebo | Percentage of Participants With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs) | Suspected ARs or Non-serious ARs | 0 Percentage of Participants |
| GLASSIA 120 mg/kg Versus Placebo | Percentage of Participants With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs) | Suspected ARs or Serious ARs | 0 Percentage of Participants |
| Placebo (Group 5) | Percentage of Participants With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs) | Suspected ARs or Non-serious ARs | 50 Percentage of Participants |
| Placebo (Group 5) | Percentage of Participants With Suspected Adverse Reactions or Serious and Non-Serious Adverse Reactions (ARs) | Suspected ARs or Serious ARs | 0 Percentage of Participants |
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.
Time frame: From start of study treatment up to early termination of the study (approximately 22 months)
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ARALAST NP 60 mg/kg Versus Placebo | Percentage of Participants With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs) | Temporally Serious TEAE Related to IP | 0 Percentage of Participants |
| ARALAST NP 60 mg/kg Versus Placebo | Percentage of Participants With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs) | Temporally Non-Serious TEAE Related to IP | 0 Percentage of Participants |
| GLASSIA 60 mg/kg Versus Placebo | Percentage of Participants With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs) | Temporally Non-Serious TEAE Related to IP | 0 Percentage of Participants |
| GLASSIA 60 mg/kg Versus Placebo | Percentage of Participants With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs) | Temporally Serious TEAE Related to IP | 0 Percentage of Participants |
| GLASSIA 120 mg/kg Versus Placebo | Percentage of Participants With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs) | Temporally Serious TEAE Related to IP | 0 Percentage of Participants |
| GLASSIA 120 mg/kg Versus Placebo | Percentage of Participants With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs) | Temporally Non-Serious TEAE Related to IP | 0 Percentage of Participants |
| Placebo (Group 5) | Percentage of Participants With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs) | Temporally Serious TEAE Related to IP | 0 Percentage of Participants |
| Placebo (Group 5) | Percentage of Participants With Temporally Related Serious and Non-Serious Treatment Emergent Adverse Events (AEs) | Temporally Non-Serious TEAE Related to IP | 50 Percentage of Participants |
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.
Time frame: Baseline, Early termination of the study (approximately 22 months)
Population: Study was early terminated due to low and slow rate of enrollment, hence, data was not collected for this efficacy endpoint.