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PH 3/4 GLASSIA SAFETY, IMMUNOGENICITY, AND BRONCHOALVEOLAR LAVAGE STUDY

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ClinicalTrials.gov Identifier: NCT02525861
Recruitment Status : Recruiting
First Posted : August 18, 2015
Last Update Posted : July 18, 2018
Sponsor:
Information provided by (Responsible Party):
Shire ( Baxalta now part of Shire )

Brief Summary:
The purpose of the study is 2-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.

Condition or disease Intervention/treatment Phase
Alpha1-antitrypsin Deficiency Biological: GLASSIA Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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
Actual Study Start Date : April 21, 2016
Estimated Primary Completion Date : May 29, 2020
Estimated Study Completion Date : May 29, 2020


Arm Intervention/treatment
Active Comparator: GLASSIA with lower particulate level
GLASSIA lot(s) produced within acceptable range, with lower particulate level
Biological: GLASSIA
60 mg/kg BW administered at a rate of 0.2 mL/kg/min

Active Comparator: GLASSIA with higher particulate level
GLASSIA lot(s) produced within acceptable range, with higher particulate level
Biological: GLASSIA
60 mg/kg BW administered at a rate of 0.2 mL/kg/min




Primary Outcome Measures :
  1. Number (proportion) of adverse events (AEs) considered potentially related to the presence of particle load in the GLASSIA solution [ Time Frame: 6 months ]
  2. Incidence of treatment-emergent adverse reactions (ARs) plus suspected ARs [ Time Frame: 6 months ]
  3. Number (proportion) of infusions that are discontinued, slowed, or interrupted due to an adverse event (AE) [ Time Frame: 6 months ]
  4. Number (proportion) of participants who develop binding and/or neutralizing anti-A1PI antibodies [ Time Frame: 6 months ]
  5. Antigenic A1PI levels in ELF [ Time Frame: 12 - 14 weeks ]
  6. Functional A1PI (also known as anti-neutrophil elastase capacity [ANEC]) levels in ELF [ Time Frame: 12 - 14 weeks ]

Secondary Outcome Measures :
  1. Incidence of treatment-emergent adverse events (AEs) [ Time Frame: 6 months ]
  2. 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 ]
  3. Number (proportion) of subjects with treatment-emergent seroconversion or positive nucleic acid test (NAT) for parvovirus B19 (B19V) [ Time Frame: 6 months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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) and an endogenous A1PI plasma levels of ≤11 μM.
  3. Screening levels of endogenous plasma (antigenic) A1PI of ≤11 μM may be collected at any time during the screening period for treatment-naïve 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 ≤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. 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 (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) ≥50% of predicted.
    2. If FEV1 is >80% predicted, then FEV1/forced vital capacity (FVC) must be <0.7. *Note: Inclusion criterion #1a and #9a 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 ≥40 millimeter(s) 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 re-screened 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 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 (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 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 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 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. The participant is a family member or employee of the investigator.
  19. If female, the participant is nursing at the time of screening.
  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.

    • Note: Exclusion criteria #20, #21, #22, #23, and #24 are not applicable to participants who are not required to undergo the bronchoscopy/BAL procedures.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02525861


Contacts
Contact: Andrea Ayad +43 1 20100 247 6779 andrea.ayad@shire.com
Contact: Shire Contact +1 866 842 5335 ClinicalTransparency@shire.com

Locations
United States, Arizona
St. Joseph's Hospital and Medical Center Withdrawn
Phoenix, Arizona, United States, 85013
United States, California
UCLA Medical Center Recruiting
Los Angeles, California, United States, 90024
Contact: Igor Barjaktarevic, MD         
Contact: John Dermand    310-206-0396    jdermand@mednet.ucla.edu   
University of California Davis Health System Recruiting
Sacramento, California, United States, 95817
Contact: Brian Morrissey, MD         
Contact: Tina Tham    916-703-4093    ttham@ucdavis.edu   
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Michael Campos, MD         
Contact: Esther Diaz    305-243-2568    eid3@med.miami.edu   
Tampa General Hospital Withdrawn
Tampa, Florida, United States, 33606
Cleveland Clinic Florida - Weston Recruiting
Weston, Florida, United States, 33331
Contact: Franck Rahaghi, MD         
Contact: Maria Briceno    954-659-6409    bricenm@ccf.org   
United States, Illinois
University of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637
Contact: Douglas Hogarth, MD         
Contact: Soumia Msallek    773-702-1012    smsallek@medicine.bsd.uchicago.edu   
United States, Kentucky
Kentucky Lung Clinic, PSC Withdrawn
Hazard, Kentucky, United States, 41701
United States, Missouri
Hannibal Clinic Recruiting
Hannibal, Missouri, United States, 63401
Contact: Humam Farah, MD         
Contact: Ellen Taylor    573-406-5870    etaylor@hannibalclinic.com   
United States, Pennsylvania
Temple University School of Medicine Recruiting
Philadelphia, Pennsylvania, United States, 19140
Contact: Friedrich Kueppers, MD         
Contact: Sylvia Johnson    215-707-4679    sylvia.johnson@tuhs.temple.edu   
United States, South Carolina
Medical University of South Carolina (MUSC) Recruiting
Charleston, South Carolina, United States, 29425
Contact: Charlton Strange III, MD         
Contact: Gwen Blanton    843-792-8438    blantonm@musc.edu   
United States, Tennessee
Clinical Research Solutions, LLC Recruiting
Franklin, Tennessee, United States, 37067
Contact: Aaron Milstone, MD         
Contact: Jessica Wallan    615-577-4017    jwallan@crssites.com   
United States, Texas
University of Texas Health Science Center at Tyler Recruiting
Tyler, Texas, United States, 75708
Contact: James Stocks, MD         
Contact: Janice Hoeft    903-877-5518    janice.hoeft@uthct.edu   
Canada, Ontario
LHSC - Victoria Hospital Recruiting
London, Ontario, Canada, N6A 5W9
Contact: David McCormack, MD         
Contact: Leila MacBean    519-685-8500 ext 74833    leila.macbean@lhsc.on.ca   
Sponsors and Collaborators
Baxalta now part of Shire
Investigators
Study Director: Study Director Shire

Responsible Party: Baxalta now part of Shire
ClinicalTrials.gov Identifier: NCT02525861     History of Changes
Other Study ID Numbers: 471101
First Posted: August 18, 2015    Key Record Dates
Last Update Posted: July 18, 2018
Last Verified: July 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Alpha 1-Antitrypsin Deficiency
Liver Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Subcutaneous Emphysema
Emphysema
Pathologic Processes
Alpha 1-Antitrypsin
Trypsin Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action