The purpose of the study is 2-fold: (1) to evaluate the safety and potential immunogenicity of GLASSIA following intravenous (IV) administration via in-line filtration; and (2) to assess the effects of GLASSIA augmentation therapy on the levels of A1PI and various biomarkers in the epithelial lining fluid (ELF) following intravenous (IV) administration at a dosage of 60 milligrams per kilogram (mg/kg) Body weight (BW)/week active alpha1-proteinase inhibitor (A1PI) protein for 25 weeks in participants with emphysema due to congenital A1PI deficiency.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
34
Participants will receive weekly IV infusions of GLASSIA at 60 mg/kg BW active A1PI protein administered at a rate of 0.2 mL/kg/min for 25 weeks (25 planned infusions) via an IV administration.
Arizona Board of Regents, University of Arizona
Tucson, Arizona, United States
UCLA Medical Center
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Potentially Related to Presence of Particle Load in the GLASSIA Solution
An Adverse Events (AEs) was defined as any untoward medical occurrence in a participant administered an IP that does not necessarily have a causal relationship with the treatment. Any AE that occurs on or after the first dose of IP infusion will be considered a TEAE. A TEAE that is considered potentially related to the presence of protein aggregates (particle load) in the GLASSIA solution is defined as any embolic or thrombotic event. Number of participants with TEAEs potentially related to the presence of protein aggregates (particle load) in the GLASSIA solution were reported.
Time frame: From start of study treatment up to Week 26
Number of Participants With Treatment-Emergent Adverse Reactions (ARs) Plus Suspected Adverse Reactions (ARs) Within 24 Hours Following the End of IP Infusion
An Treatment-emergent AR and suspected AR was any TEAE which met any of the following criteria: a; A TEAE that began during infusion or within 24 hours (or 1 day where time of onset is not available) following the end of IP infusion, or b; A TEAE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or c; A TEAE for which causality assessment was missing or indeterminate. Number of participants with both treatment-emergent ARs plus suspected ARs were collectively reported.
Time frame: From start of study treatment up to 24 hours post infusion
Number of Participants With Treatment-Emergent Adverse Reactions (ARs) Plus Suspected Adverse Reactions (ARs) Within 72 Hours Following the End of IP Infusion
An Treatment-emergent AR and suspected AR was any TEAE which met any of the following criteria: a; A TEAE that began during infusion or within 72 hours (or 3 days where time of onset is not available) following the end of IP infusion, or b; A TEAE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or c; A TEAE for which causality assessment was missing or indeterminate. Number of participants with both treatment-emergent ARs plus suspected ARs were collectively reported.
Time frame: From start of study treatment up to 72 hours post infusion
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Los Angeles, California, United States
Cedars Sinai Medical Center, Division of Pulmonary and Critical Care Medicine
Los Angeles, California, United States
University of California Davis Health System
Sacramento, California, United States
University of Miami
Miami, Florida, United States
DBC Research Corp, Pembroke Pines
Tamarac, Florida, United States
Cleveland Clinic Florida - Weston
Weston, Florida, United States
University of Chicago Medical Center
Chicago, Illinois, United States
LaPorte County Institute for Clinical Research, Inc.
Michigan City, Indiana, United States
Pulmonary Critical Care Associates of Baltimore
Towson, Maryland, United States
...and 8 more locations
Number of Infusions Discontinued, Slowed, or Interrupted Due to TEAEs
An 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. Infusions may be interrupted or discontinued in an individual participant in the event of intolerable moderate to severe infusion-related AEs and/or at the discretion of the investigator. Number of infusions that are discontinued, slowed, or interrupted due to TEAEs were reported.
Time frame: From start of study treatment up to Week 26
Number of Participants Who Developed Binding and/or Neutralizing Anti- Alpha1-Proteinase Inhibitor(A1PI) Antibodies
Development of Binding/Neutralizing Anti-A1PI Antibodies=Negative or missing at Baseline and confirmed positive at any post-infusion time point. Participants that had a positive result at Baseline and missing at all post-infusion time points were included as "No Development". Neutralizing anti-A1PI antibodies were only assessed in case of positive binding anti-A1PI antibodies. Anti-A1PI antibodies was detected using validated binding and neutralizing anti-A1PI antibody assays at a qualified immunoassay laboratory. Number of participants who developed binding and/or neutralizing anti-A1PI antibodies were reported.
Time frame: From start of study treatment up to Week 26
Change From Baseline in Antigenic Alpha1-Proteinase Inhibitor (A1PI) Levels in Epithelial Lining Fluid (ELF)
Change from baseline in antigenic A1PI levels in ELF up to Week 14 was reported. Bronchoalveolar Lavage (BAL) procedures were performed at baseline and on-treatment BAL visit during GLASSIA augmentation therapy. Data for this outcome measure was analyzed and planned to be reported based on overall arm (Arms/Groups were combined as pre-specified in the study protocol).
Time frame: Baseline up to Week 14
Change From Baseline in Functional Alpha1-Proteinase Inhibitor(A1PI) Levels in Epithelial Lining Fluid (ELF)
Change from baseline in functional A1PI (also known as Anti-Neutrophil Elastase Capacity \[ANEC\]) levels in ELF up to Week 14 was reported. BAL procedures were performed at baseline and on-treatment BAL visit during GLASSIA augmentation therapy. Data for this outcome measure was analyzed and planned to be reported based on overall arm (Arms/Groups were combined as pre-specified in the study protocol).
Time frame: Baseline up to Week 14
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An AEs was defined as any untoward medical occurrence in a participant administered an IP that does not necessarily have a causal relationship with the treatment. Any AE that occurs on or after the first dose of IP infusion will be considered a TEAE.
Time frame: From start of study treatment up to Week 26
Number of Participants Who Experienced a Shift From Normal or Clinically Non-significant Abnormal Laboratory Values at Baseline to Clinically Significant Abnormal Laboratory Values at Week 13, 25, and 26
Clinical laboratory values included Hematology (hemoglobin, leukocytes, neutrophils, reticulocytes/erythrocytes \[Ret/Ery\], platelets); Chemistry (sodium, potassium, albumin, alanine aminotransferase \[AA\], aspartate aminotransferase \[ASA\], alkaline phosphatase \[AP\], lactate dehydrogenase \[LD\], gamma glutamyl transferase \[GGT\], bilirubin, direct bilirubin \[DB\], creatinine, creatine kinase \[CK\], glucose); Urinalysis (erythrocytes urine \[EU\], protein urine \[PU\], specific gravity \[SG\], pH) and Immunology (Complement C3, Complement C4). Assessment if a value was normal, clinically non-significant abnormal, or clinically significant abnormal was done by the investigator. Number of participants who experienced a shift from normal or clinically non-significant (NCS) abnormal laboratory values at baseline \[BL\] to clinically significant (CS) abnormal laboratory values at Week 13, 25 and 26 were reported.
Time frame: Baseline, Week 13, 25 and 26
Number of Participants With Treatment-Emergent Seroconversion or Positive Nucleic Acid Test (NAT) for Parvovirus B19 (B19V)
Viral testing for B19V consisted of viral serology or NAT for B19V (Parvovirus B19 IgG Antibody, Parvovirus B19 IgM Antibody, Parvovirus B19 DNA Quant real-time polymerase chain reaction \[RT-PCR\]). Number of participants with treatment-emergent seroconversion or positive NAT for B19V were reported.
Time frame: From start of study treatment up to Week 26