GLASSIA Infusion Rate Study

Study Overview
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Brief Summary
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The purpose of this study was to generate sufficient safety and tolerability information in support of an increase in the infusion rate of intravenous GLASSIA in the prescribing information from 0.04 to 0.2 mL/kg/min.

Detailed Description
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To achieve proper masking, 30 participants were randomly assigned to receive either GLASSIA at 0.04 mL/kg/min with a simultaneous administration of placebo (2.5% human albumin in normal saline) at 0.2 mL/kg/min (Cohort 1) or GLASSIA at 0.2 mL/kg/min with a simultaneous administration of placebo at 0.04 mL/kg/min (Cohort 2) on Day 1. Two weeks later (Day 15), the same participants received the second infusion with the opposite rate of GLASSIA infusion and the corresponding masking placebo infusion.

Official Title
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A Phase 4 Double-Blind Study to Assess the Safety and Tolerability of Intravenous Administration of GLASSIA in Healthy Adult Volunteers

Conditions
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Alpha1-antitrypsin Deficiency, Healthy Volunteers

Intervention / Treatment
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* Biological: Alpha1-proteinase inhibitor
* Biological: Placebo: Human albumin 2.5%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 to 65 years of age inclusive, at the time of screening Body mass index (BMI) in the range of 19.0 to 32.0 kg/m2 (inclusive) and body weight >= 50 kg at the time of screening Healthy subject with no clinical evidence of acute and/or chronic disease and no clinically significant abnormalities on hematology panel, clinical chemistry panel, urinalysis, or electrocardiogram (ECG) at the time of screening Negative drug screen test at screening. Subject must agree to refrain from heavy alcohol consumption (defined as more than 2 drinks per day on a regular basis) and use of narcotic drugs or illegal substances for at least 2 weeks prior to screening and throughout the course of the study. Subject must also agree to drug screen testing at the discretion of the investigator at any time during the course of the study. If female of childbearing potential, subject presents with a negative serum pregnancy test and agrees to employ adequate birth control measures for the duration of the study If male, the subject must agree to use an acceptable form of birth control throughout the study and for at least 90 days after dosing. Additionally, the subject must agree to abstain from sperm donation for 90 days after the last administration of investigational product. Subject is willing and able to comply with the requirements of the protocol Exclusion Criteria: 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 Known history of hypersensitivity or adverse reactions (e.g. urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following administration of blood or blood components Documented immunoglobulin A (IgA) deficiency (<7 mg/dL at screening) Evidence of uncontrolled hypertension (systolic blood pressure of >160 mm Hg, and/or diastolic blood pressure of >100 mm Hg despite anti-hypertensive medications) Subject is nursing or intends to begin nursing during the course of the study Subject has participated in a clinical trial and has received an investigational product within 60 days prior to screening Subject has a planned medical procedure within the study period Any clinically significant medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, may impede the subject's ability to comply with the study procedures, pose increased risk to the subject's safety, or confound the interpretation of study results

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Day 1: GLASSIA at 0.04 mL/kg/min Placebo at 0.2 mL/kg/min Day 15: GLASSIA at 0.2 mL/kg/min Placebo at 0.04 mL/kg/min | Biological: Alpha1-proteinase inhibitor<br>* GLASSIA will be supplied as a sterile, non-pyrogenic, ready-to-use solution, in single dose 50 mL vials; for intravenous administration.<br>* Other names: GLASSIA;Biological: Placebo: Human albumin 2.5%<br>* Intravenous administration<br>|
| Experimental: Cohort 2<br>Day 1: GLASSIA at 0.2 mL/kg/min Placebo at 0.04 mL/kg/min Day 15: GLASSIA at 0.04 mL/kg/min Placebo at 0.2 mL/kg/min | Biological: Alpha1-proteinase inhibitor<br>* GLASSIA will be supplied as a sterile, non-pyrogenic, ready-to-use solution, in single dose 50 mL vials; for intravenous administration.<br>* Other names: GLASSIA;Biological: Placebo: Human albumin 2.5%<br>* Intravenous administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Infusions Associated With a Reduction in Infusion Rate or Discontinuation of Infusion Due to an Adverse Event (Regardless of Adverse Event Causality Assessment) |  | Day 1 and Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Infusions With Temporally Associated Adverse Events (AEs) That Began During or Within 1 Hour of Infusion Completion | Number of infusions with temporally associated AEs with an onset time during or within 1 hour of infusion completion, regardless of causality assessment | Within 1 hour of infusion completion | 
| Number of Infusions With Temporally Associated Adverse Events (AEs) That Began During or Within 24 Hours of Completion of an Infusion | Number of infusions with temporally associated AEs with an onset time during or within 24 hours of infusion completion, regardless of causality assessment | Within 24 hours of the end of infusion | 
| Number of Infusions With Temporally Associated Adverse Events (AEs) That Began During or Within 72 Hours of Completion of an Infusion | Number of infusions with temporally associated AEs with an onset time during or within 72 hours of infusion completion, regardless of causality assessment | Within 72 hours of the end of infusion | 
| Number of Possibly or Probably Related Adverse Events (AEs) That Began During an Infusion | Number of AEs that occurred during an infusion and were deemed related to study product administration | Day 1 and Day 15 | 
| Number of Possibly or Probably Related Adverse Events That Occurred Between 72 Hours and 14 Days After Infusion | Number of AEs that occurred between 72 hours and 14 day following an infusion and were deemed related to study product administration | 72 hours post infusion to 14 days post infusion | 
| Number of Participants Testing Positive for Hepatitis A Virus (HAV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Parvovirus B19 (PVB19) or Human Immunodeficiency Virus (HIV) Following Treatment With GLASSIA | Number of participants with seroconversion | 105 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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for this study, volunteers, Focus, Condition: