Experimental Treatment with GLASSIA in Patients With Low A1PI Levels (condition where certain enzymes attack healthy lung tissue)

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"This study is being conducted to look at how well the study drug is able to increase your A1PI levels."
Age: 18 years or older
Gender:
Any
Healthy Volunteers: No
Keywords: A1PI-Deficiency, A1PI-Deficient, Epithelial Lining Fluid, ELF, Alpha1-Proteinase Inhibitor, A1PI
Type: Biological study, Phase 3
Target:
5 Participants
Investigator:
Description
GLASSIA is a purified alpha1-proteinase inhibitor. Alpha-1 proteinase inhibitor is a medicine used to treat conditions where certain enzymes attack healthy tissues, especially the lungs.

It has been approved by the FDA since 2010 for the treatment of emphysema due to severe hereditary deficiency of A1PI. Many commonly-used drugs contain tiny particles that are invisible to the naked eye. The FDA limits the number of particles in each vial of an approved drug.

This study is being conducted to look at how well the study drug is able to increase your A1PI levels. This will be tested in the bronchoalveolar epithelial lining fluid (ELF) before and after treatment with GLASSIA. ELF is the fluid that is in contact with the tiny airways and air sacs in the lungs.

GLASSIA will also be referred to as the “study drug”. This treatment with the study drug is considered “investigational.” Although GLASSIA is FDA approved, we are evaluating:
- Any differences in symptoms and side effects with a higher particle number.
- Any differences in symptoms and side effects with a lower particle number.
- How your immune system may react to the study drug.
- How well the study drug is able to increase the A1PI level in the lungs.
This study requires

SCREENING

If you decide to be in this study, you will complete a series of tests to check that you meet study requirements:

-Informed Consent -Eligibility Check -Medical and Medication History -Physical Exam -Height and Weight -Vital Signs -Chest X-ray/CT Chest Scan -Pulmonary Function Tests -Blood Draw -Urine Test -Pregnancy Test -Adverse Events

BASELINE

You may undergo a test called bronchoalveolar lavage (BAL) during the baseline visit. This is a medical test in which a bronchoscope is passed through your mouth or nose into the lungs. A bronchoscope is a thin flexible tube with a camera and light source at the end. Once the study doctor reaches the targeted airway, a small amount of fluid is released into the airway. It is then collected to test for the levels of A1PI in the lining of your lungs. The study doctor will use standard medications for this test. Your heart will be monitored as well as your blood pressure, breathing and pulse.

A blood test will be collected on the same day of your BAL visit. After the BAL test, you will be contacted by phone or asked to return to the site in person in approximately 2 weeks to check on your health status.

There will be a group of subjects that will complete the BAL test and a separate group that will not. The group that completes the BAL will be enrolled first. You may not have to undergo a BAL once the target number of BAL subjects has been reached. If you are not eligible to undergo the BAL test based on your medical history, the test may be waived. You may still be able to participate in the study with sponsor approval before the target number of subjects for the BAL test has been reached. The study team will let you know whether or not you will have to undergo the BAL procedure.

RANDOMIZATION

If you meet the study requirements and you agree to be in this study, you will be assigned to one of two groups:

-GLASSIA (high particles) or -GLASSIA (low particles)

Your group assignment will be decided by a process called randomization. This means that the drug choice will be determined by chance, like flipping a coin. There is a 50% chance that you will be assigned to one group over the other. This is a double-blind study which means that you and the study team will not know to which group you are assigned. However, in the event of an emergency, this information can be made available.

WEEKLY STUDY DRUG INFUSIONS

After you are randomized, the study drug will be given to you through one of your veins (intravenous infusions). At this dose and rate, each study drug infusion will take approximately 15 minutes. There will be a total of 25 infusions over approximately 6 months. The dose of study drug given to you in this study is the dose approved by the FDA. Study drug infusions may take place at the study site or at another suitable location, like your home. If the study doctor allows for home infusions and you choose to have the drug given in your home, a home care nurse will visit your home and perform the infusion. Please be aware that the study drug infusions at Weeks 1, 7, 13, 19, and 25 must be done at the study site.

FOLLOW-UP VISITS (WEEKS 1, 7, 13, 19, AND 25)

There will be at least five visits where you will be asked to return to the study site. At these visits, the following will be performed:

-Body Weight -Physical Exam -Vital Signs -Blood Draw -Urine Test (Weeks 1, 13, and 25 only) -Pregnancy Test -Adverse Events -Concomitant Medications and Non-Drug Therapies -Infusion

BAL VISIT (WEEKS 12-14)

You will be asked to come in for one BAL visit sometime in between Weeks 12-14. The visit will be similar to the BAL procedure that you had at the Baseline Visit. You may not have to undergo this visit if the study has approximately 15-18 patients whom have completed a BAL for the study or if your participation in the BAL portion of the study is waived by the sponsor. However, if you completed a BAL at your Baseline visit, you will likely have to undergo this test during Weeks 12-14 (even if the required number of patients has been reached). The study team will let you know whether or not you will have to undergo this test.

END OF STUDY (WEEK 26) or EARLY TERMINATION VISIT

Once you have finished the last dose of the study drug, you will be asked to return to the study site approximately one week later to have the following tests performed:

-Blood Draw -Urine Test -Pregnancy Test -Adverse Events -Concomitant Medications and Non-Drug Therapies

If you are discontinued from the study early and have had at least one dose of study drug, you will be asked to return to the site approximately 1 week after your last infusion to complete the above tests.

Who can participate

Inclusion criteria:

  1. Male or female participants meeting the following age criteria:
  2. For participants who will undergo bronchoscopy/ bronchoalveolar lavage (BAL) procedures: 18 to 75 years of age at the time of screening.
  3. For participants who will be waived from undergoing bronchoscopy/BAL procedures: 18 years of age or older at the time of screening.
  4. Documented Alpha1-Proteinase Inhibitor (A1PI) genotype of PiZ/Z, PiZ/Null, PiMalton/Z, PiNull/Null, or other "at-risk" allelic combinations such as SZ (excluding MS and MZ) and an endogenous A1PI plasma levels of ≤11 μM.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. The participant is willing and able to comply with the requirements of the protocol.
  11. The participant must have pulmonary function at the time of screening meeting both of the following:
  12. Post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥50% of predicted.
  13. 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:
  15. Serum alanine aminotransferase (ALT) >3.0 times upper limit of normal (ULN)
  16. Serum total bilirubin >2.0 times ULN
  17. 2+proteinuria on urine dipstick analysis

  18. Serum creatinine >2.0 times ULN
  19. Absolute neutrophil count (ANC) <1500 cells/mm^3
  20. Hemoglobin (Hgb) <9.0 g/dL
  21. Platelet count <100,000/mm^3
  22. 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.
  23. 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.
  24. 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.
  25. The participant is a family member or employee of the investigator.
  26. If female, the participant is nursing at the time of screening.
  27. 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.
  28. The participant has had lung surgery which may interfere with bronchoscopy.
  29. 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.
  30. 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.
  31. 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.
  32. Note: Exclusion criteria #20, #21, #22, #23, and #24 are not applicable to participants who are not required to undergo the bronchoscopy/BAL procedures.
Benefits and risks of participating
BENEFITS:

We cannot promise any benefits to you or others from your taking part in this research. Possible benefits include improvement of lung conditions after treatment with the study drug. Other patients may benefit in the future based on what we learned from this study.


RISKS:

With any study products, there may also be risks associated with the use of study drug - both known and unknown. The study doctor will discuss the potential risks associated with taking part in this research study. You will be made aware of any new information or risks as they become known to the study team.
Compensation
We will compensate you $100 for each study visit that you complete on-site.
Resources
Schedule
Study duration and period
We expect your participation to last for about 8 months.
Recruitment period
From May 9, 2016
Location
UC Davis Medical Center
2315 Stockton Boulevard
Sacramento, CA 95817
Research Topic
Conditions:
  • Alpha1-antitrypsin Deficiency