GLASSIA Infusion Rate Study

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Alpha1-antitrypsin Deficiency
• Intervention / Treatment: Biological: Alpha1-proteinase inhibitor; Biological: Placebo: Human albumin 2.5%

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 66211

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 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; GLASSIA will be supplied as a sterile, non-pyrogenic, ready-to-use solution, in single dose 50 mL vials; for intravenous administration.; Other Names: GLASSIA; Biological: Placebo: Human albumin 2.5%; Intravenous administration
Experimental: Cohort 2; 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; GLASSIA will be supplied as a sterile, non-pyrogenic, ready-to-use solution, in single dose 50 mL vials; for intravenous administration.; Other Names: GLASSIA; Biological: Placebo: Human albumin 2.5%; Intravenous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Baxalta now part of Shire

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2012
• Primary Completion (Actual): January 16, 2013
• Study Completion (Actual): January 16, 2013

Study Registration Dates

• First Submitted: July 23, 2012
• First Submitted That Met QC Criteria: July 25, 2012
• First Posted (Estimate): July 27, 2012

Study Record Updates

• Last Update Posted (Actual): May 25, 2021
• Last Update Submitted That Met QC Criteria: May 3, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: volunteers; Focus; for this study; Condition:
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Liver Diseases; Genetic Diseases, Inborn; Subcutaneous Emphysema; Emphysema; Alpha 1-Antitrypsin Deficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Serine Proteinase Inhibitors; Trypsin Inhibitors; Protease Inhibitors; Alpha 1-Antitrypsin
• Other Study ID Numbers: 471201