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Alpha1-antitrypsin DeficiencyPhase 3NCT02525861

GLASSIA Safety, Immunogenicity, and Bronchoalveolar Lavage Study

A Phase 3 study testing GLASSIA in people with Alpha1-antitrypsin Deficiency, run by Baxalta now part of Shire at 18 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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)… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Alpha1-antitrypsin Deficiency
What is being tested?
GLASSIA
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
18 sitesin 2 countries
Study dates
8 Mar 2016to 29 Jul 2020
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • If FEV1 is >80% predicted, then FEV1/forced vital capacity (FVC) must be <0.7. *Note: Inclusion criterion #1a, #9a and #9b are not applicable to participants who are not required to undergo the bronchoscopy/BAL procedures.

Who cannot join

  • 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).
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  • 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)
  • Serum total bilirubin >2.0 times ULN
  • >2+proteinuria on urine dipstick analysis
  • Serum creatinine >2.0 times ULN
  • Absolute neutrophil count (ANC) <1500 cells per cubic millimeter (cells/mm^3)
  • Hemoglobin (Hgb) <9.0 gram per deciliter (g/dL)
  • Platelet count <100,000/cubic millimeter (mm^3)
  • Ongoing active infection with hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) Type 1 or 2 infection at the time of screening.
  • The participant has any clinically significant medical, psychiatric, or cognitive illness, or any other uncontrolled medical condition (eg, unstable angina, transient ischemic attack) that, in the opinion of the investigator, would impede the participant's ability to comply with the study procedures, pose increased risk to the participant's safety, or confound the interpretation of study results.
  • The participant has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or device during the course of this study.
  • The participant is a family member or employee of the investigator.
  • If female, the participant is nursing at the time of screening.
  • Note: Exclusion criteria #20, #21, #22, #23, and #24 are not applicable to participants who are not required to undergo the bronchoscopy/BAL procedures.
  • The participant has contraindication(s) to bronchoscopy such as recent myocardial infarction, unstable angina, other cardiopulmonary instability, tracheal obstruction or stenosis, moderate to severe hypoxemia or any degree of hypercapnia, unstable asthma, Stage 4 or 5 chronic kidney disease, pulmonary hypertension, severe hemorrhagic diathesis, and cervical C1/C2 arthritis.
  • The participant has had lung surgery which may interfere with bronchoscopy.
  • Known history of allergic/hypersensitivity reactions to medications used during and for perioperative care associated with the bronchoscopy/BAL procedures, such as local anesthetics, sedatives, pain control medications.
  • The participant is receiving or requires long-term (>4 weeks) immunosuppressive therapy, such as systemic corticosteroids at doses greater than 10 mg/day of prednisone (or its equivalent), mycophenolate mofetil, azathioprine, cyclophosphamide, and rituximab.
  • If a participant is receiving anticoagulant or anti-platelet therapy (such as warfarin and clopidogrel), the participant is unwilling to or unable to safely discontinue anticoagulant or anti-platelet therapy within 7 days prior to until at least 24 hours after the BAL procedures. An exception is low-dose aspirin alone which is allowed.

Trial locations and contacts

18 sites in 2 countries.

18 sites in 2 countries

United States17 sites

  • Medical University of South Carolina (MUSC)

    Charleston, South Carolina, 29425

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Dayton Respiratory Research Center

    Dayton, Ohio, 45415

  • Hannibal Clinic

    Hannibal, Missouri, 63401

  • UCLA Medical Center

    Los Angeles, California, 90024

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

    Los Angeles, California, 90048

  • University of Miami

    Miami, Florida, 33136

  • LaPorte County Institute for Clinical Research, Inc.

    Michigan City, Indiana, 46360

  • Temple University School of Medicine

    Philadelphia, Pennsylvania, 19140

  • University of California Davis Health System

    Sacramento, California, 95817

  • DBC Research Corp, Pembroke Pines

    Tamarac, Florida, 33321

  • Renovatio Clinical-Respiratory & Sleep Disorders Specialists

    The Woodlands, Texas, 77005

  • Pulmonary Critical Care Associates of Baltimore

    Towson, Maryland, 21286

  • Arizona Board of Regents, University of Arizona

    Tucson, Arizona, 85724

  • University of Texas Health Science Center at Tyler

    Tyler, Texas, 75708

  • Cleveland Clinic Florida - Weston

    Weston, Florida, 33331

  • Southeastern Research Center LLC

    Winston-Salem, North Carolina, 27103

Other trials in United States

Canada1 site

  • LHSC - Victoria Hospital

    London, Ontario, N6A 5W9

Other trials in Canada

About this study

Official title: A Phase 3/4 Study to Evaluate the Safety, Immunogenicity, and Effects on the Alpha1-Proteinase Inhibitor (A1PI) Levels in Epithelial Lining Fluid Following Glassia Therapy in A1PI-Deficient Subjects

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.

Being tested
GLASSIA
Medical subject headings
alpha 1-Antitrypsin Deficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GLASSIABiological

    Also called Alpha1-Proteinase Inhibitor, A1PI

    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.

Study groups in NCT02525861
Study groupRoleWhat they receive
Cohort I: GLASSIA (High-end)ExperimentalParticipants 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.
Receives: Biological: GLASSIA
Cohort II: GLASSIA (Low-end)ExperimentalParticipants 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.
Receives: Biological: GLASSIA

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: From start of study treatment up to Week 26

  2. 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.

    Measured: From start of study treatment up to 24 hours post infusion

  3. 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.

    Measured: From start of study treatment up to 72 hours post infusion

  4. 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.

    Measured: From start of study treatment up to Week 26

  5. 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.

    Measured: From start of study treatment up to Week 26

  6. 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).

    Measured: Baseline up to Week 14

  7. 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).

    Measured: Baseline up to Week 14

Secondary outcomes (3)

  1. 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.

    Measured: From start of study treatment up to Week 26

  2. 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.

    Measured: Baseline, Week 13, 25 and 26

  3. 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.

    Measured: From start of study treatment up to Week 26

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Aug 2015 (estimated)
  2. Study start8 Mar 2016
  3. Primary completion29 Jul 2020
  4. Study completion29 Jul 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02525861
Sponsor's protocol ID
471101
Status last verified
Jul 2021
First submitted
14 Aug 2015
Last updated
14 Oct 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing GLASSIA in people with Alpha1-antitrypsin Deficiency, run by Baxalta now part of Shire at 18 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Potentially Related to Presence of Particle Load in the GLASSIA Solution (time frame: From start of study treatment up to Week 26). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02525861.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2021.

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