Clinical trial NCT02614872: Study to Evaluate the Safety and Efficacy of Intravenous Glassia® Treatment in Lung Transplantation
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Transplantation, Lung Rejection
Lead sponsor: Kamada, Ltd.
Sponsor class: INDUSTRY
First posted: 2015-11-25
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluates the safety and efficacy of intravenous GLASSIA® treatment in lung transplantation.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Signed and dated informed consent.
2. Age ≥18 years.
3. Subject is planned to undergo first single or double lung transplant (including heart-lung transplant) as per standard implantation procedure.

Exclusion Criteria:

1. Subject has immunoglobulin A (IgA) deficiency and known anti IgA antibodies.
2. 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
3. Subjects with a history of severe immediate hypersensitivity reactions, including allergies, anaphylaxis to plasma products or any human proteins of different source.
4. 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.
5. 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.
6. Alcohol abuse or history of alcohol abuse.
7. Illegal drugs.
8. Candidate for organ transplantation other than first lung or heart-lung transplantation
9. Clinically significant bronchial stenosis unresponsive to dilation and/or stenting
10. Participation in another interventional clinical trial within 30 days prior to baseline visit.
11. Inability to attend scheduled clinic visits and/or comply with the study protocol.
12. Any other factor that, in the opinion of the investigator, would prevent the subject from complying with the requirements of the protocol.

Primary outcomes:
measure: Incidence of subjects experiencing AEs and/or SAEs
timeFrame: during the study
measure: Incidence and rate of Acute Rejection
timeFrame: per year
Secondary outcomes:
measure: Annual rate (per subject) of pulmonary infections
timeFrame: per year
measure: Incidence of subjects who develop Bronchiolitis Obliterans
timeFrame: during the study
measure: Changes in Pulmonary Function Test
timeFrame: Change from baseline and overall effect
Other outcomes:
Locations:
city: Petach Tikva
country: Israel
facility: Pulmonary Institute - Rabin Medical Center
Study officials:
affiliation: Pulmonary institute, Rabin Medical Center, Israel.
name: Mordechai Kramer, MD
role: PRINCIPAL_INVESTIGATOR
References: