Alpha1-antitrypsin Deficiency, Healthy Volunteers
Conditions
Keywords
for this study, volunteers, Focus, Condition:
Brief summary
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
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.
Interventions
BIOLOGICALAlpha1-proteinase inhibitor
GLASSIA will be supplied as a sterile, non-pyrogenic, ready-to-use solution, in single dose 50 mL vials; for intravenous administration.
BIOLOGICALPlacebo: Human albumin 2.5%
Intravenous administration
Sponsors
Baxalta now part of Shire
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Infusions With Temporally Associated Adverse Events (AEs) That Began During or Within 24 Hours of Completion of an Infusion | Within 24 hours of the end of infusion | Number of infusions with temporally associated AEs with an onset time during or within 24 hours of infusion completion, regardless of causality assessment |
| Number of Infusions With Temporally Associated Adverse Events (AEs) That Began During or Within 72 Hours of Completion of an Infusion | Within 72 hours of the end of infusion | Number of infusions with temporally associated AEs with an onset time during or within 72 hours of infusion completion, regardless of causality assessment |
| Number of Infusions With Temporally Associated Adverse Events (AEs) That Began During or Within 1 Hour of Infusion Completion | 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 |
| Number of Possibly or Probably Related Adverse Events That Occurred Between 72 Hours and 14 Days After Infusion | 72 hours post infusion to 14 days post infusion | Number of AEs that occurred between 72 hours and 14 day following an infusion and were deemed related to study product administration |
| 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 | 105 days | Number of participants with seroconversion |
| Number of Possibly or Probably Related Adverse Events (AEs) That Began During an Infusion | Day 1 and Day 15 | Number of AEs that occurred during an infusion and were deemed related to study product administration |
Countries
United States
Participant flow
Recruitment details
Recruitment was conducted in the U.S at 1 study site. The first participant was enrolled in July 2012.
Pre-assignment details
Thirty five healthy potential participants were enrolled at the clinical study site. Four were screen failures, and one was a back up participant who did not participate. Therefore, 30 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| 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 Placebo: Human albumin 2.5%: Intravenous administration | 15 |
| 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 Placebo: Human albumin 2.5%: Intravenous administration | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|
| Age, Continuous | 27 years STANDARD_DEVIATION 8 | 29 years STANDARD_DEVIATION 13 | 28 years STANDARD_DEVIATION 11 |
| Region of Enrollment United States | 15 Participants | 15 Participants | 30 Participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 12 Participants | 11 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 30 | 4 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
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)
Time frame: Day 1 and Day 15
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLASSIA at 0.04 mL/kg/Min + Placebo at 0.2 mL/kg/Min | 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) | 0 Infusions |
| GLASSIA at 0.2 mL/kg/Min + Placebo at 0.04 mL/kg/Min | 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) | 0 Infusions |
Secondary
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
Time frame: Within 1 hour of infusion completion
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLASSIA at 0.04 mL/kg/Min + Placebo at 0.2 mL/kg/Min | Number of Infusions With Temporally Associated Adverse Events (AEs) That Began During or Within 1 Hour of Infusion Completion | 3 Infusions |
| GLASSIA at 0.2 mL/kg/Min + Placebo at 0.04 mL/kg/Min | Number of Infusions With Temporally Associated Adverse Events (AEs) That Began During or Within 1 Hour of Infusion Completion | 1 Infusions |
Secondary
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
Time frame: Within 24 hours of the end of infusion
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLASSIA at 0.04 mL/kg/Min + Placebo at 0.2 mL/kg/Min | Number of Infusions With Temporally Associated Adverse Events (AEs) That Began During or Within 24 Hours of Completion of an Infusion | 5 Infusions |
| GLASSIA at 0.2 mL/kg/Min + Placebo at 0.04 mL/kg/Min | Number of Infusions With Temporally Associated Adverse Events (AEs) That Began During or Within 24 Hours of Completion of an Infusion | 3 Infusions |
Secondary
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
Time frame: Within 72 hours of the end of infusion
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLASSIA at 0.04 mL/kg/Min + Placebo at 0.2 mL/kg/Min | Number of Infusions With Temporally Associated Adverse Events (AEs) That Began During or Within 72 Hours of Completion of an Infusion | 7 Infusions |
| GLASSIA at 0.2 mL/kg/Min + Placebo at 0.04 mL/kg/Min | Number of Infusions With Temporally Associated Adverse Events (AEs) That Began During or Within 72 Hours of Completion of an Infusion | 5 Infusions |
Secondary
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
Time frame: 105 days
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GLASSIA at 0.04 mL/kg/Min + Placebo at 0.2 mL/kg/Min | 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 | HAV | 0 participants |
| GLASSIA at 0.04 mL/kg/Min + Placebo at 0.2 mL/kg/Min | 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 | HBV | 0 participants |
| GLASSIA at 0.04 mL/kg/Min + Placebo at 0.2 mL/kg/Min | 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 | HCV | 0 participants |
| GLASSIA at 0.04 mL/kg/Min + Placebo at 0.2 mL/kg/Min | 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 | PVB19 | 0 participants |
| GLASSIA at 0.04 mL/kg/Min + Placebo at 0.2 mL/kg/Min | 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 | HIV | 0 participants |
Secondary
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
Time frame: Day 1 and Day 15
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLASSIA at 0.04 mL/kg/Min + Placebo at 0.2 mL/kg/Min | Number of Possibly or Probably Related Adverse Events (AEs) That Began During an Infusion | 1 adverse events |
| GLASSIA at 0.2 mL/kg/Min + Placebo at 0.04 mL/kg/Min | Number of Possibly or Probably Related Adverse Events (AEs) That Began During an Infusion | 0 adverse events |
Secondary
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
Time frame: 72 hours post infusion to 14 days post infusion
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLASSIA at 0.04 mL/kg/Min + Placebo at 0.2 mL/kg/Min | Number of Possibly or Probably Related Adverse Events That Occurred Between 72 Hours and 14 Days After Infusion | 0 adverse events |
| GLASSIA at 0.2 mL/kg/Min + Placebo at 0.04 mL/kg/Min | Number of Possibly or Probably Related Adverse Events That Occurred Between 72 Hours and 14 Days After Infusion | 0 adverse events |