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GLASSIA Safety, Immunogenicity, and Bronchoalveolar Lavage Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02525861
Recruitment Status : Active, not recruiting
First Posted : August 18, 2015
Last Update Posted : April 28, 2020
Sponsor:
Information provided by (Responsible Party):
Shire ( Baxalta now part of Shire )

Tracking Information
First Submitted Date  ICMJE August 14, 2015
First Posted Date  ICMJE August 18, 2015
Last Update Posted Date April 28, 2020
Actual Study Start Date  ICMJE April 21, 2016
Estimated Primary Completion Date July 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 18, 2019)
  • Number of Adverse Events (AEs) Considered Potentially Related to the Presence of Particle Load in the GLASSIA Solution [ Time Frame: From start of study up to end of study (Week 26) ]
    An AE is defined as any untoward medical occurrence in a participant administered an investigational produtc (IP) that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of the IP, whether or not considered causally related to the IP. Number of AEs considered potentially related to the presence of particle load in the GLASSIA solution will be assessed.
  • Incidence of Treatment-Emergent Adverse Reactions (ARs) plus Suspected Adverse Reactions (ARs) [ Time Frame: From start of study up to end of study (Week 26) ]
    An AR plus suspected AR is any which met any of the following criteria: a) an AE that began during infusion or within 72 hours following the end of IP infusion, or b) an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or c) an AE for which causality assessment was missing or indeterminate. Incidence of treatment-emergent adverse reactions (ARs) plus suspected ARs will be assessed.
  • Number of Infusions that are Discontinued, Slowed, or Interrupted due to an Adverse Event (AE) [ Time Frame: From start of study up to end of study (Week 26) ]
    An AE is defined as any untoward medical occurrence in a participant administered an investigational produtc (IP) that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of the IP, whether or not considered causally related to the IP. Number of infusions that are discontinued, slowed, or interrupted due to an AE will be assessed.
  • Number of Participants who Develop Binding and/or Neutralizing Anti- Alpha1-Proteinase Inhibitor(A1PI) Antibodies at Week 1 [ Time Frame: Week 1 ]
    Number of participants who develop binding and/or neutralizing anti-A1PI antibodies at week 1 will be assessed.
  • Number of Participants who Develop Binding and/or Neutralizing Anti- Alpha1-Proteinase Inhibitor(A1PI) Antibodies at Week 13 [ Time Frame: Week 13 ]
    Number of participants who develop binding and/or neutralizing anti-A1PI antibodies at week 13 will be assessed.
  • Number of Participants who Develop Binding and/or Neutralizing Anti- Alpha1-Proteinase Inhibitor(A1PI) Antibodies at Week 25 [ Time Frame: Week 25 ]
    Number of participants who develop binding and/or neutralizing anti-A1PI antibodies at week 25 will be assessed.
  • Number of Participants who Develop Binding and/or Neutralizing Anti- Alpha1-Proteinase Inhibitor(A1PI) Antibodies at Week 26 [ Time Frame: Week 26 ]
    Number of participants who develop binding and/or neutralizing anti-A1PI antibodies at week 26 will be assessed.
  • Change From Baseline in Antigenic Alpha1-Proteinase Inhibitor(A1PI) Levels in Epithelial Lining Fluid (ELF) [ Time Frame: Baseline, 12 to 14 Weeks ]
    Change from baseline in antigenic A1PI levels in ELF will be assessed.
  • Change From Baseline in Functional Alpha1-Proteinase Inhibitor(A1PI) Levels in Epithelial Lining Fluid (ELF) [ Time Frame: Baseline, 12 to 14 Weeks ]
    Change from baseline in functional A1PI (also known as Anti-Neutrophil Elastase Capacity [ANEC]) levels in ELF will be assessed.
Original Primary Outcome Measures  ICMJE
 (submitted: August 14, 2015)
  • Number (proportion) of adverse events (AEs) considered potentially related to the presence of protein aggregates in the GLASSIA solution [ Time Frame: 6 months ]
  • Incidence of treatment-emergent adverse reactions (ARs) plus suspected ARs [ Time Frame: 6 months ]
  • Number (proportion) of infusions that are discontinued, slowed, or interrupted due to an adverse event (AE) [ Time Frame: 6 months ]
  • Number (proportion) of participants who develop binding and/or neutralizing anti-A1PI antibodies [ Time Frame: 6 months ]
  • Antigenic A1PI levels in ELF [ Time Frame: 12 - 14 weeks ]
  • Functional A1PI (also known as anti-neutrophil elastase capacity [ANEC]) levels in ELF [ Time Frame: 12 - 14 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 18, 2019)
  • Incidence of Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: From start of study up to end of study (Week 26) ]
    Incidence of TEAEs will be assessed.
  • Number of Participants With Shift from Normal or Clinically Insignificant Abnormal Laboratory Values at Baseline to Clinically Significant Abnormal Laboratory Values Following GLASSIA Administration [ Time Frame: From start of study up to end of study (Week 26) ]
    Number of participants with shift from normal or clinically insignificant abnormal laboratory values at baseline to clinically significant abnormal laboratory values following GLASSIA administration will be assessed.
  • Number of Participants with Treatment-Emergent Seroconversion or Positive Nucleic Acid Test (NAT) for Parvovirus B19 (B19V) [ Time Frame: From start of study up to end of study (Week 26) ]
    Viral testing for B19V will consist of B19V antibody serology test and NAT, based on real-time polymerase chain reaction (PCR) detection of B19V DNA. Number of participants with treatment-emergent seroconversion or positive nucleic acid test (NAT) for parvovirus B19 (B19V) will be assessed.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 14, 2015)
  • Incidence of treatment-emergent adverse events (AEs) [ Time Frame: 6 months ]
  • Number (proportion) of participants who experienced a shift from normal or clinically insignificant abnormal laboratory values at baseline to clinically significant abnormal laboratory values following GLASSIA administration [ Time Frame: 6 months ]
  • Number (proportion) of subjects with treatment-emergent seroconversion or positive nucleic acid test (NAT) for parvovirus B19 (B19V) [ Time Frame: 6 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE GLASSIA Safety, Immunogenicity, and Bronchoalveolar Lavage Study
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Alpha1-antitrypsin Deficiency
Intervention  ICMJE Biological: GLASSIA
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.
Other Names:
  • Alpha1-Proteinase Inhibitor
  • A1PI
Study Arms  ICMJE
  • Experimental: Cohort I
    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.
    Intervention: Biological: GLASSIA
  • Experimental: Cohort II
    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.
    Intervention: Biological: GLASSIA
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 27, 2020)
34
Original Estimated Enrollment  ICMJE
 (submitted: August 14, 2015)
36
Estimated Study Completion Date  ICMJE July 31, 2020
Estimated Primary Completion Date July 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female participants meeting the following age criteria:

    1. For participants who will undergo bronchoscopy/ bronchoalveolar lavage (BAL) procedures: 18 to 75 years of age at the time of screening.
    2. For participants who will be waived from undergoing bronchoscopy/BAL procedures: 18 years of age or older at the time of screening.
  2. 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]).
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. The participant is willing and able to comply with the requirements of the protocol.
  9. The participant must have pulmonary function at the time of screening meeting both of the following:

    1. Post-bronchodilator forced expiratory volume in 1 second (FEV1) greater than or equal to (> or =) 50 percentage (%) of predicted.
    2. 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.

Exclusion Criteria:

  1. 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).
  2. 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]).
  3. The participant routinely produces more than 1 tablespoon of sputum per day.
  4. The participant has a history of frequent pulmonary exacerbations (greater than 2 moderate or severe exacerbations within 52 weeks prior to screening.
  5. 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).
  6. 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).
  7. 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).
  8. The participant has clinically significant congestive heart failure with New York Heart Association (NYHA) Class III/IV symptoms.
  9. 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.
  10. The participant has a history of lung or other organ transplant, is currently on a transplant list, or has undergone major lung surgery.
  11. 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]).
  12. Known history of hypersensitivity following infusions of human blood or blood components.
  13. Immunoglobulin A (IgA) deficiency (<8 milligram per deciliter (mg/dL) at screening).
  14. Abnormal clinical laboratory results obtained at the time of screening meeting any of the following criteria:

    1. Serum alanine aminotransferase (ALT) >3.0 times upper limit of normal (ULN)
    2. Serum total bilirubin >2.0 times ULN
    3. >2+proteinuria on urine dipstick analysis
    4. Serum creatinine >2.0 times ULN
    5. Absolute neutrophil count (ANC) <1500 cells per cubic millimeter (cells/mm^3)
    6. Hemoglobin (Hgb) <9.0 gram per deciliter (g/dL)
    7. Platelet count <100,000/cubic millimeter (mm^3)
  15. 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.
  16. 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.
  17. 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.
  18. The participant is a family member or employee of the investigator.
  19. 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.

  20. 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.
  21. The participant has had lung surgery which may interfere with bronchoscopy.
  22. 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.
  23. 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.
  24. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02525861
Other Study ID Numbers  ICMJE 471101
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Shire provides access to the de-identified individual participant data for eligible studies to aid qualified researchers in addressing legitimate scientific objectives. These IPDs will be provided following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.shiretrials.com website. 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.
URL: https://www.shiretrials.com/en/our-commitment-to-transparency/data-sharing-with-researchers
Responsible Party Shire ( Baxalta now part of Shire )
Study Sponsor  ICMJE Baxalta now part of Shire
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Study Director Shire
PRS Account Shire
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP