GLASSIA Safety, Immunogenicity, and Bronchoalveolar Lavage Study

NCT02525861 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 471101
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 18

Brief Summary

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.

Conditions

Alpha1-antitrypsin Deficiency

Outcome Measures

Primary Outcomes (7)

• 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.

  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.

  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.

  From start of study treatment up to 72 hours post infusion

• 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.

  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.

  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).

  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).

  Baseline up to Week 14

Secondary Outcomes (3)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  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

  Baseline, Week 13, 25 and 26

• Number of Participants With Treatment-Emergent Seroconversion or Positive Nucleic Acid Test (NAT) for Parvovirus B19 (B19V)

  From start of study treatment up to Week 26

Study Arms (2)

Cohort I: GLASSIA (High-end)

EXPERIMENTAL

Participants will receive weekly IV infusions of GLASSIA (lot with particle loads representing the high end within) at 60 milligrams per kilogram (mg/kg) BW active A1PI protein administered at a rate of 0.2 milliliters per kilogram of body weight per minute (ml/kg/min) for 25 weeks (25 planned infusions) via an IV administration.

Biological: GLASSIA

Cohort II: GLASSIA (Low-end)

EXPERIMENTAL

Participants will receive weekly IV infusions of GLASSIA (lot with particle loads representing the low end within the normal range) 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.

Biological: GLASSIA

Interventions

GLASSIA BIOLOGICAL

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.

Also known as: Alpha1-Proteinase Inhibitor, A1PI

Cohort I: GLASSIA (High-end); Cohort II: GLASSIA (Low-end)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants meeting the following age criteria:
• For participants who will undergo bronchoscopy/ bronchoalveolar lavage (BAL) procedures: 18 to 75 years of age at the time of screening.
• For participants who will be waived from undergoing bronchoscopy/BAL procedures: 18 years of age or older at the time of screening.
• Documented Alpha1-Proteinase Inhibitor (A1PI) genotype of Pi\*Z/Z, Pi\*Z/Null, Pi\*Malton/Z, Pi\*Null/Null, or other "at-risk" allelic combinations such as SZ (excluding MS and MZ without the presence of another allowable at-risk genotype) and an endogenous A1PI plasma levels of less than or equal to (\< or =)11 micrometer (μM) (\< or = 0.572 milligrams per milliliter \[mg/mL\]).
• Screening levels of endogenous plasma (antigenic) A1PI of \< or =11 μM may be collected at any time during the screening period for treatment-naive participants, or following a 4 week minimum wash-out from previous augmentation therapy in treatment-experienced participants.
• Participants must have at least one of the following: clinical diagnosis of emphysema, evidence of emphysema on computerized tomography (CT) scan of the chest, and/or evidence of airway obstruction which is not completely reversed with bronchodilator treatment at the time of screening.
• If the participant is being treated with any respiratory medications including inhaled bronchodilators, inhaled anticholinergics, inhaled corticosteroids, or low-dose systemic corticosteroids (prednisone \< or =10 milligram per day (mg/day) or its equivalent), the doses of the participant's medications have remained unchanged for at least 14 days prior to screening.
• The participant is a nonsmoker or has ceased smoking for a minimum of 13 weeks prior to screening (serum cotinine level at screening within normal range of a nonsmoker) and agrees to refrain from smoking throughout the course of the study. Participants with a positive cotinine test due to nicotine replacement therapy (example \[eg\], patches, chewing gum), vapor cigarettes, or snuff are eligible.
• If female of childbearing potential, the participant presents with a negative pregnancy test at screening and agrees to employ adequate birth control measures for the duration of the study.
• The participant is willing and able to comply with the requirements of the protocol.
• The participant must have pulmonary function at the time of screening meeting both of the following:
• Post-bronchodilator forced expiratory volume in 1 second (FEV1) greater than or equal to (\> or =) 50 percentage (%) of predicted.

You may not qualify if:

• The participant is experiencing or has a history of clinically significant pulmonary disease (other than chronic obstructive pulmonary disease (COPD), emphysema, chronic bronchitis, mild bronchiectasis, and stable asthma).
• The participant is experiencing or has a history of chronic severe cor pulmonale (resting mean pulmonary artery pressure \> or =40 millimeters) of mercury \[mm Hg\]).
• The participant routinely produces more than 1 tablespoon of sputum per day.
• The participant has a history of frequent pulmonary exacerbations (greater than 2 moderate or severe exacerbations within 52 weeks prior to screening.
• The participant is experiencing a pulmonary exacerbation at the time of screening (participant may be rescreened 4 weeks after the clinical resolution of an exacerbation).
• The participant has clinically significant abnormalities (other than emphysema, chronic bronchitis, or mild bronchiectasis) detected on chest X-ray or CT scan at the time of screening (past records obtained within 52 weeks prior to screening may be used, if available).
• The participant has clinically significant abnormalities detected on a 12-lead electrocardiogram (ECG) performed at the time of screening (past records obtained within 26 weeks prior to screening may be used, if available).
• The participant has clinically significant congestive heart failure with New York Heart Association (NYHA) Class III/IV symptoms.
• The participant is experiencing an active malignancy or has a history of malignancy within 5 years prior to screening, with the exception of the following: adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or stable prostate cancer not requiring treatment.
• The participant has a history of lung or other organ transplant, is currently on a transplant list, or has undergone major lung surgery.
• The participant is receiving long-term around-the-clock oxygen (O2) supplementation. (The following are allowed: short-term use of oxygen supplementation \[eg, for the management of acute COPD exacerbation\], O2 supplementation required during night time only, and supplemental O2 with continuous positive airway pressure \[CPAP\] or bi-level positive airway pressure \[BiPAP\]).
• Known history of hypersensitivity following infusions of human blood or blood components.
• Immunoglobulin A (IgA) deficiency (\<8 milligram per deciliter (mg/dL) at screening).
• Abnormal clinical laboratory results obtained at the time of screening meeting any of the following criteria:
• Serum alanine aminotransferase (ALT) \>3.0 times upper limit of normal (ULN)

Sponsors & Collaborators

• Baxalta now part of Shire: lead

Study Sites (18)

Arizona Board of Regents, University of Arizona

Tucson, Arizona, 85724, United States

Location

UCLA Medical Center

Los Angeles, California, 90024, United States

Location

Cedars Sinai Medical Center, Division of Pulmonary and Critical Care Medicine

Los Angeles, California, 90048, United States

Location

University of California Davis Health System

Sacramento, California, 95817, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

DBC Research Corp, Pembroke Pines

Tamarac, Florida, 33321, United States

Location

Cleveland Clinic Florida - Weston

Weston, Florida, 33331, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

LaPorte County Institute for Clinical Research, Inc.

Michigan City, Indiana, 46360, United States

Location

Pulmonary Critical Care Associates of Baltimore

Towson, Maryland, 21286, United States

Location

Hannibal Clinic

Hannibal, Missouri, 63401, United States

Location

Southeastern Research Center LLC

Winston-Salem, North Carolina, 27103, United States

Location

Dayton Respiratory Research Center

Dayton, Ohio, 45415, United States

Location

Temple University School of Medicine

Philadelphia, Pennsylvania, 19140, United States

Location

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

Location

Renovatio Clinical-Respiratory & Sleep Disorders Specialists

The Woodlands, Texas, 77005, United States

Location

University of Texas Health Science Center at Tyler

Tyler, Texas, 75708, United States

Location

LHSC - Victoria Hospital

London, Ontario, N6A 5W9, Canada

Location

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency

Interventions

alpha 1-Antitrypsin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Acute-Phase Proteins; Blood Proteins; Proteins; Alpha-Globulins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Baxalta

ClinicalTransparency@takeda.com

+1 866 842 5335

Study Officials

• Study Director

  Shire

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2015
• First Posted: August 18, 2015
• Study Start: March 8, 2016
• Primary Completion: July 29, 2020
• Study Completion: July 29, 2020
• Last Updated: October 14, 2021
• Results First Posted: October 14, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

US (17); CA (1)