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Ph 3/4 GLASSIA Safety, Immunogenicity, and Bronchoalveolar Lavage Study

This study is currently recruiting participants.
Verified September 2017 by Shire ( Baxalta now part of Shire )
Sponsor:
ClinicalTrials.gov Identifier:
NCT02525861
First Posted: August 18, 2015
Last Update Posted: October 23, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Shire ( Baxalta now part of Shire )
August 14, 2015
August 18, 2015
October 23, 2017
March 8, 2016
February 26, 2018   (Final data collection date for primary outcome measure)
  • Number (proportion) of adverse events (AEs) considered potentially related to the presence of particle load 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 ]
  • 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 ]
Complete list of historical versions of study NCT02525861 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Ph 3/4 GLASSIA Safety, Immunogenicity, and Bronchoalveolar Lavage Study
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 two-fold: (1) to further evaluate the safety and potential immunogenicity of GLASSIA following 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 mg/kg Body weight (BW)/week active A1PI protein for 25 weeks in subjects with emphysema due to congenital A1PI deficiency.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Alpha1-antitrypsin Deficiency
Biological: GLASSIA
60 mg/kg BW administered at a rate of 0.2 mL/kg/min
  • Active Comparator: GLASSIA with lower particulate level
    GLASSIA lot(s) produced within acceptable range, with lower particulate level
    Intervention: Biological: GLASSIA
  • Active Comparator: GLASSIA with higher particulate level
    GLASSIA lot(s) produced within acceptable range, with higher particulate level
    Intervention: Biological: GLASSIA
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
36
February 26, 2018
February 26, 2018   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • 1. Male or female:

    1. For participants who will undergo bronchoscopy/BAL procedures: 18 to 65 years of age.
    2. For participants who will be waived from undergoing bronchoscopy/BAL procedures (after adequate number of BAL evaluable participants has been reached): 18 years of age or older.
  • 2. A1PI genotype of Pi*Z/Z, Pi*Z/Null, Pi*Malton/Z, Pi*Null/Null, or other "at-risk" allelic combinations (excluding MS, MZ, and SZ)
  • 3. Endogenous plasma (antigenic) A1PI level of <8 μM.
  • 4. Participant 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. Participant is being treated with any respiratory medications including inhaled bronchodilators, inhaled anticholinergics, inhaled corticosteroids, or low-dose systemic corticosteroids (prednisone ≤10 mg/day or its equivalent), the doses of the participant's medications have remained unchanged for at least 14 days prior to screening.
  • 6. 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.
  • 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. Participant is willing and able to comply with the requirements of the protocol.
  • 9. 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) ≥50% of predicted
    2. If FEV1 is >80% predicted, then FEV1/forced vital capacity (FVC) must be <0.7. **Note: Inclusion criterion #8 is not applicable to participants who are enrolled after the target of 15 to 18 evaluable participants has been reached and who are therefore not required to undergo the bronchoscopy/BAL procedures.

Exclusion Criteria:

  • 1. Participant is experiencing or has a history of clinically significant pulmonary disease (other than COPD, emphysema, chronic bronchitis, mild bronchiectasis, and stable asthma).
  • 2. Participant is experiencing or has a history of cor pulmonale.
  • 3. Participant routinely produces more than one tablespoon of sputum per day.
  • 4. Participant has a history of frequent pulmonary exacerbations (greater than 2 moderate or severe exacerbations within 52 weeks prior to screening.
  • 5. Participant is experiencing a pulmonary exacerbation at the time of screening (participant may be re-screened 4 weeks after the clinical resolution of an exacerbation).
  • 6. 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. 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. Participant has clinically significant congestive heart failure with New York Heart Association (NYHA) Class III/IV symptoms.
  • 9. 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. Participant has a history of lung or other organ transplant, is currently on a transplant list, or has undergone major lung surgery.
  • 11. Participant is receiving long-term around-the-clock oxygen supplementation. (The following are allowed: short-term use of oxygen supplementation (eg, for the management of acute COPD exacerbation), oxygen supplementation required during night time only, and supplemental oxygen 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 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/mm^3
    6. Hemoglobin (Hgb) <9.0 g/dL
    7. Platelet count <100,000/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 1/2 infection at the time of screening.
  • 16. 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. Participant has participated in another clinical study involving an investigational product or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an investigational product or device during the course of this study.
  • 18. Participant is a family member or employee of the investigator.
  • 19. If female, the participant is nursing at the time of screening.
  • 20. 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. 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. 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.

    • Note: Exclusion criteria #20, 21, 22, 23, and 24 are not applicable to participants who are enrolled after the target of 15 to 18 evaluable participants has been reached and who are therefore not required to undergo the bronchoscopy/BAL procedures.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact: Melanie Narciso +43-1-20-100-247-3672 Melanie.Narciso@shire.com
Canada,   United States
 
 
NCT02525861
471101
No
Not Provided
Not Provided
Shire ( Baxalta now part of Shire )
Baxalta now part of Shire
Not Provided
Study Director: Abhijit Bapat, MD, PhD Baxalta now part of Shire
Shire
September 2017

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