Study to Evaluate the Safety and Efficacy of Intravenous Glassia® Treatment in Lung Transplantation

Study Overview
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Brief Summary
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This study evaluates the safety and efficacy of intravenous GLASSIA® treatment in lung transplantation.

Detailed Description
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There is clinical rationale to advocate the use of AAT(GLASSIA) therapy during episodes of lung inflammation, including acute and chronic rejection. AAT may provide more specifically targeted prevention of pathogenic inflammation, superior to that of general immunosuppressants, with little risk. AAT is the main inhibitor of Neutrophil elastase(NE) in the lower airways and patients with AAT deficiency have low concentrations of the protein in this region of the lung. This explains the proteinase/antiproteinase theory of the development of emphysema in deficient patients in which the amount of elastase released in the lung exceeds the amount of AAT. The net result is persistence of elastase activity leading to lung destruction and the pathological changes of emphysema. Administration of AAT will help to prevent further destruction of the lung architecture and reduce the inflammatory dysregulation that causes pulmonary dysfunction. It is expected that by attacking a specific and previously untreated key component of the pathophysiological cycle of BOS, AAT therapy would decrease the prevalence of BOS in lung transplant recipients and prolong life expectancy of these patients. This will be an open label study in order to ensure safety, in the frame of POC study.

Official Title
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A Proof of Concept (POC) Study, Phase II, Open Label, Randomized, Standard Care - Controlled, Single Center Study Evaluating the Safety and Efficacy of Human, Alpha-1 Antitrypsin (AAT) [GLASSIA®] Treatment in First Lung Transplantation

Conditions
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Transplantation, Lung Rejection

Intervention / Treatment
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* Drug: GLASSIA® and Institution standard of care (SOC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent. Age ≥18 years. Subject is planned to undergo first single or double lung transplant (including heart-lung transplant) as per standard implantation procedure. Exclusion Criteria: Subject has immunoglobulin A (IgA) deficiency and known anti IgA antibodies. Known history of OR positive serological evidence at the time of screening for hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), Parvovirus B19 (PVB19) or human immunodeficiency virus (HIV) Type 1/2 infection Subjects with a history of severe immediate hypersensitivity reactions, including allergies, anaphylaxis to plasma products or any human proteins of different source. Pregnant or lactating women at entry to study and women of child bearing potential, who are unwilling to agree to continue to use acceptable methods of contraception throughout the study. Presence of psychiatric/ mental disorder or any other medical disorder which might impair the subject's ability to give informed consent or to comply with the requirements of the study protocol. Alcohol abuse or history of alcohol abuse. Illegal drugs. Candidate for organ transplantation other than first lung or heart-lung transplantation Clinically significant bronchial stenosis unresponsive to dilation and/or stenting Participation in another interventional clinical trial within 30 days prior to baseline visit. Inability to attend scheduled clinic visits and/or comply with the study protocol. Any other factor that, in the opinion of the investigator, would prevent the subject from complying with the requirements of the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLASSIA®<br>Glassia® IV treatment additional to Institution standard of care (SOC) for first lung transplant subjects according to Investigator discretion. | Drug: GLASSIA® and Institution standard of care (SOC)<br>* Alpha-1 Antitrypsin (AAT) [GLASSIA®] add-on pharmacotherapy and Institution standard of care (SOC)<br>* Other names: GLASSIA and Institution standard of care (SOC);|
| No Intervention: Institution standard of care (SOC)<br>Institution standard of care (SOC) for first lung transplant subjects according to Investigator discretion. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of subjects experiencing AEs and/or SAEs | Incidence of subjects experiencing causally related AEs and/or SAEs | during the study | 
| Incidence and rate of Acute Rejection | Incidence and rate of Acute Rejection | per year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annual rate (per subject) of pulmonary infections | Annual rate (per subject) of pulmonary infections | per year | 
| Incidence of subjects who develop Bronchiolitis Obliterans | Incidence of subjects who develop Bronchiolitis Obliterans | during the study | 
| Changes in Pulmonary Function Test | Changes in Pulmonary Function Test | Change from baseline and overall effect |