Stage 1 Study of ARALAST NP and GLASSIA in A1PI Deficiency
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)
1 other identifier
interventional
7
3 countries
17
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3 chronic-obstructive-pulmonary-disease
Started Nov 2016
Typical duration for phase_3 chronic-obstructive-pulmonary-disease
17 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 23, 2016
CompletedFirst Posted
Study publicly available on registry
March 30, 2016
CompletedStudy Start
First participant enrolled
November 2, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 14, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
September 14, 2018
CompletedResults Posted
Study results publicly available
October 8, 2019
CompletedMay 13, 2021
April 1, 2021
1.9 years
March 23, 2016
September 18, 2019
April 17, 2021
Conditions
Outcome Measures
Primary Outcomes (1)
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)
Secondary Outcomes (10)
Rate of Change in Lung Density for Each Treatment Group
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
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)
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)
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)
From start of study treatment up to early termination of the study (approximately 22 months)
- +5 more secondary outcomes
Study Arms (5)
ARALAST NP 60 mg/kg
EXPERIMENTAL60 mg/kg body weight/week
ARALAST NP 120 mg/kg
EXPERIMENTAL120 mg/kg body weight/week
GLASSIA 60 mg/kg
EXPERIMENTAL60 mg/kg body weight/week
GLASSIA 120 mg/kg
EXPERIMENTAL120 mg/kg body weight/week
Placebo
PLACEBO COMPARATORHuman Albumin 2%
Interventions
ARALAST NP is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy
ARALAST NP is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy
GLASSIA is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy
GLASSIA is an Alpha1-Proteinase Inhibitor (A1PI) augmentation therapy
Human albumin 2% (by appropriate dilution with normal saline solution)
Eligibility Criteria
You may qualify if:
- ≥18 years of age at the time of screening
- 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).
- Clinically evident mild-moderate chronic obstructive pulmonary disease (COPD) (according to GOLD criteria for diagnosis) at the time of screening.
- 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.
- 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.
- 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.
- Participant is willing and able to comply with the requirements of the protocol.
You may not qualify if:
- 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).
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (17)
Phoenix Medical Research Institute, LLC
Peoria, Arizona, 85381, United States
Newport Native MD, Inc
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
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
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.
Results Point of Contact
- Title
- Study Director
- Organization
- Shire
Study Officials
- STUDY DIRECTOR
Study Director
Takeda
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 23, 2016
First Posted
March 30, 2016
Study Start
November 2, 2016
Primary Completion
September 14, 2018
Study Completion
September 14, 2018
Last Updated
May 13, 2021
Results First Posted
October 8, 2019
Record last verified: 2021-04
Data Sharing
- IPD Sharing
- Will not share
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).