GLASSIA Safety, Immunogenicity, and Bronchoalveolar Lavage Study

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Brief Title

GLASSIA Safety, Immunogenicity, and Bronchoalveolar Lavage 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

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.
    


Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Number of Adverse Events (AEs) Considered Potentially Related to the Presence of Particle Load in the GLASSIA Solution

Secondary Outcome

 Incidence of Treatment-Emergent Adverse Events (TEAEs)

Condition

Alpha1-antitrypsin Deficiency

Intervention

GLASSIA

Study Arms / Comparison Groups

 Cohort I
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

34

Start Date

April 21, 2016

Completion Date

July 31, 2020

Primary Completion Date

July 31, 2020

Eligibility 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 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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Study Director, , 

Location Countries

Canada

Location Countries

Canada

Administrative Informations


NCT ID

NCT02525861

Organization ID

471101


Responsible Party

Sponsor

Study Sponsor

Baxalta now part of Shire


Study Sponsor

Study Director, Study Director, Shire


Verification Date

April 2020