Immunologic Deficiency Syndromes
Conditions
Brief summary
The purpose of this study is to evaluate the safety, efficacy and Pharmacokinetics of Immune Globulin Intravenous (Human) GC5107 in subjects with Primary Humoral Immunodeficiency (PHID).
Detailed description
This was a prospective, open-label, single-arm, historically controlled, multicenter phase 3 study measuring the safety, efficacy and pharmacokinetics and tolerability of GC5107 in subjects with Primary Humoral Immunodeficiency disease (PHID). Subjects received intravenous infusions of the investigational product at the same dose and interval as used for their previous Immunoglobulin intravenous (IVIG) maintenance therapy. GC5107 was administered every 21 or 28 days for a period of 12 months.
Interventions
BIOLOGICALGC5107
GC5107 20g/200mL, intravenously, dose of 300 - 900 mg/kg (of body weight) every 21 or 28 days for 12 months, a follow-up (3 or 4 weeks)
Sponsors
Parexel
Atlantic Research Group
Green Cross Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Subject with a confirmed clinical diagnosis of a Primary Humoral Immunodeficiency Disease as defined by IUIS (International Union of Immunological Societies) and require treatment with IGIV. Documented agammaglobulinemia or hypogammaglobulinemia * Male or Female, ages 2 to 70 years * The subject has received 300-900 mg/kg of a licensed IGIV therapy at 21 or 28 day intervals for at least 3 months prior to this study * At least 2 documented IgG trough levels of ≥ 500 mg/dL are obtained at two infusion cycles (21 or 28 days) within 12 months prior to study enrollment
Exclusion criteria
* Subject has secondary immunodeficiency * Subject was newly diagnosed with PHID and has not yet been treated with immunoglobulin * Subject has been diagnosed with dysgammaglobulinemia or isolated IgG subclass deficiency or isolated IgA deficiency with known anti-IgA antibodies * History of severe reaction or hypersensitivity to IGIV or other injectable form of IgG * Subject has a lifetime history of at least one thrombotic event including deep vein thrombosis, cerebrovascular accident, pulmonary embolism, transient ischemic attacks, or myocardial infarction * Subject has received blood products other than human albumin or human immunoglobulin within 12 months prior to enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Incidence of Acute Serious Bacterial Infections (SBI) | One year | The incidence of acute serious bacterial infections (aSBIs) meeting FDA guidance criteria, which includes bacterial pneumonia, bacteremia/sepsis, bacterial meningitis, visceral abscesses, and osteomyelitis/septic arthritis. Efficacy data is evaluated by comparing the frequency of acute serious bacterial infections per subject per year according to the FDA guideline of an upper one-sided 99% confidence limit \< 1.0 per subject per year. |
| The Proportion of Infusions With Temporally Associated Adverse Events (TAAEs) That Occur Within 72 Hours Following an Infusion of Test Product | Within 72 hours after an infusion of GC5107 | The proportion of infusions with temporally associated adverse events occurring during or within 72 hours following infusion, whether or not they were thought to be related to GC5107 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Days of Unscheduled Physician Visits Due to Infections | One year | Based on the total number of days of unscheduled physician visits due to infections for each subject. Mean and SD are calculated based on weighting for the duration of data available for each subject, where duration is defined as (date of last visit - first infusion date + 1) for subjects who complete the study; and defined as (date of withdrawal - first infusion date + 1) for subjects who withdraw from the study. |
| The Number of Days of Hospitalizations Due to Infections | One year | Subject with no experience of specific event will be included in the analysis as zero incidence, zero day, or zero time duration. The mean and SD will be calculated weighting for the duration of data available for each subject. |
| The Incidence of Infections Other Than Acute Serious Bacterial Infections | One year | — |
| The Number of Days of Oral Therapeutic Antibiotics | One year | Based on the total number of days of oral (PO) therapeutic antibiotics for each subject. Mean and SD are calculated based on weighting for the duration of data available for each subject, where duration is defined as (date of last visit - first infusion date + 1) for subjects who complete the study; and defined as (date of withdrawal - first infusion date + 1) for subjects who withdraw from the study. |
| The Number of Days of Intravenous (IV) Therapeutic Antibiotics | One year | Based on the total number of days of IV therapeutic antibiotics for each subject. Mean and SD are calculated based on weighting for the duration of data available for each subject, where duration is defined as (date of last visit -first infusion date + 1) for subjects who complete the study; and defined as (date of withdrawal - first infusion date + 1) for subjects who withdraw from the study. |
| The Number of Days Missed From Work/School/Kindergarten/Daycare, or Days Unable to Perform Normal Daily Activities Due to Infections | One year | Based on the total number of days missed from work/school/kindergarten/daycare or days unable to perform normal daily activities due to infections for each subject. Mean and SD are calculated based on weighting for the duration of data available for each subject, where duration is defined as (date of last visit - first infusion date + 1) for subjects who complete the study; and defined as (date of withdrawal - first infusion date + 1) for subjects who withdraw from the study. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 28-day Infusion Infusion every 28 days | 29 |
| 21-day Infusion Infusion every 21 days | 20 |
| Total | 49 |
Baseline characteristics
| Characteristic | 21-day Infusion | Total | 28-day Infusion |
|---|---|---|---|
| Age, Continuous | 30.7 years STANDARD_DEVIATION 23.2 | 37.1 years STANDARD_DEVIATION 22.7 | 41.5 years STANDARD_DEVIATION 21.7 |
| Duration since first IVIG infusion | 8.8 years STANDARD_DEVIATION 6.7 | 8.8 years STANDARD_DEVIATION 7.6 | 8.8 years STANDARD_DEVIATION 8.3 |
| IVIG dose prior to enrollment | 592.7 mg/kg STANDARD_DEVIATION 135.9 | 538.5 mg/kg STANDARD_DEVIATION 120.6 | 501.2 mg/kg STANDARD_DEVIATION 94 |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 19 Participants | 47 Participants | 28 Participants |
| Region of Enrollment Canada | 2 Participants | 13 Participants | 11 Participants |
| Region of Enrollment United States | 18 Participants | 36 Participants | 18 Participants |
| Sex: Female, Male Female | 8 Participants | 21 Participants | 13 Participants |
| Sex: Female, Male Male | 12 Participants | 28 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 49 |
| other Total, other adverse events | 49 / 49 |
| serious Total, serious adverse events | 4 / 49 |
Outcome results
Primary
The Incidence of Acute Serious Bacterial Infections (SBI)
The incidence of acute serious bacterial infections (aSBIs) meeting FDA guidance criteria, which includes bacterial pneumonia, bacteremia/sepsis, bacterial meningitis, visceral abscesses, and osteomyelitis/septic arthritis. Efficacy data is evaluated by comparing the frequency of acute serious bacterial infections per subject per year according to the FDA guideline of an upper one-sided 99% confidence limit \< 1.0 per subject per year.
Time frame: One year
Population: Intent-to-Treat (ITT) Population: Defined as of all subjects who were enrolled into the study and received any amount of the IMP. This population was used for display of demographics, disposition, and for the primary safety and efficacy analyses
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 28-day Schedule | The Incidence of Acute Serious Bacterial Infections (SBI) | 0.04 Number of events per patient per year |
| 21-day Schedule | The Incidence of Acute Serious Bacterial Infections (SBI) | 0 Number of events per patient per year |
| Total | The Incidence of Acute Serious Bacterial Infections (SBI) | 0.02 Number of events per patient per year |
Primary
The Proportion of Infusions With Temporally Associated Adverse Events (TAAEs) That Occur Within 72 Hours Following an Infusion of Test Product
The proportion of infusions with temporally associated adverse events occurring during or within 72 hours following infusion, whether or not they were thought to be related to GC5107
Time frame: Within 72 hours after an infusion of GC5107
Population: Intent-to-Treat (ITT) Population: Defined as of all subjects who were enrolled into the study and received any amount of the IMP. This population was used for display of demographics, disposition, and for the primary safety and efficacy analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 28-day Schedule | The Proportion of Infusions With Temporally Associated Adverse Events (TAAEs) That Occur Within 72 Hours Following an Infusion of Test Product | 0.31 Proportion of infusion with TAAEs |
| 21-day Schedule | The Proportion of Infusions With Temporally Associated Adverse Events (TAAEs) That Occur Within 72 Hours Following an Infusion of Test Product | 0.16 Proportion of infusion with TAAEs |
| Total | The Proportion of Infusions With Temporally Associated Adverse Events (TAAEs) That Occur Within 72 Hours Following an Infusion of Test Product | 0.24 Proportion of infusion with TAAEs |
Secondary
The Incidence of Infections Other Than Acute Serious Bacterial Infections
Time frame: One year
Population: Intent-to-Treat (ITT) Population: Defined as of all subjects who were enrolled into the study and received any amount of the IMP. This population was used for display of demographics, disposition, and for the primary safety and efficacy analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 28-day Schedule | The Incidence of Infections Other Than Acute Serious Bacterial Infections | 2.4 Numberof infections per patient per year |
| 21-day Schedule | The Incidence of Infections Other Than Acute Serious Bacterial Infections | 3.6 Numberof infections per patient per year |
| Total | The Incidence of Infections Other Than Acute Serious Bacterial Infections | 2.9 Numberof infections per patient per year |
Secondary
The Number of Days Missed From Work/School/Kindergarten/Daycare, or Days Unable to Perform Normal Daily Activities Due to Infections
Based on the total number of days missed from work/school/kindergarten/daycare or days unable to perform normal daily activities due to infections for each subject. Mean and SD are calculated based on weighting for the duration of data available for each subject, where duration is defined as (date of last visit - first infusion date + 1) for subjects who complete the study; and defined as (date of withdrawal - first infusion date + 1) for subjects who withdraw from the study.
Time frame: One year
Population: Intent-to-Treat (ITT) Population: Defined as of all subjects who were enrolled into the study and received any amount of the IMP. This population was used for display of demographics, disposition, and for the primary safety and efficacy analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 28-day Schedule | The Number of Days Missed From Work/School/Kindergarten/Daycare, or Days Unable to Perform Normal Daily Activities Due to Infections | 2.9 Days | Standard Deviation 4.2 |
| 21-day Schedule | The Number of Days Missed From Work/School/Kindergarten/Daycare, or Days Unable to Perform Normal Daily Activities Due to Infections | 12.7 Days | Standard Deviation 26.11 |
| Total | The Number of Days Missed From Work/School/Kindergarten/Daycare, or Days Unable to Perform Normal Daily Activities Due to Infections | 7.1 Days | Standard Deviation 18.04 |
Secondary
The Number of Days of Hospitalizations Due to Infections
Subject with no experience of specific event will be included in the analysis as zero incidence, zero day, or zero time duration. The mean and SD will be calculated weighting for the duration of data available for each subject.
Time frame: One year
Population: Intent-to-Treat (ITT) Population: Defined as of all subjects who were enrolled into the study and received any amount of the IMP. This population was used for display of demographics, disposition, and for the primary safety and efficacy analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 28-day Schedule | The Number of Days of Hospitalizations Due to Infections | 0.1 Days | Standard Deviation 0.57 |
| 21-day Schedule | The Number of Days of Hospitalizations Due to Infections | 0.1 Days | Standard Deviation 0.46 |
| Total | The Number of Days of Hospitalizations Due to Infections | 0.1 Days | Standard Deviation 0.53 |
Secondary
The Number of Days of Intravenous (IV) Therapeutic Antibiotics
Based on the total number of days of IV therapeutic antibiotics for each subject. Mean and SD are calculated based on weighting for the duration of data available for each subject, where duration is defined as (date of last visit -first infusion date + 1) for subjects who complete the study; and defined as (date of withdrawal - first infusion date + 1) for subjects who withdraw from the study.
Time frame: One year
Population: Intent-to-Treat (ITT) Population: Defined as of all subjects who were enrolled into the study and received any amount of the IMP. This population was used for display of demographics, disposition, and for the primary safety and efficacy analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 28-day Schedule | The Number of Days of Intravenous (IV) Therapeutic Antibiotics | 0.1 Days | Standard Deviation 0.57 |
| 21-day Schedule | The Number of Days of Intravenous (IV) Therapeutic Antibiotics | 0.0 Days | Standard Deviation 0 |
| Total | The Number of Days of Intravenous (IV) Therapeutic Antibiotics | 0.1 Days | Standard Deviation 0.44 |
Secondary
The Number of Days of Oral Therapeutic Antibiotics
Based on the total number of days of oral (PO) therapeutic antibiotics for each subject. Mean and SD are calculated based on weighting for the duration of data available for each subject, where duration is defined as (date of last visit - first infusion date + 1) for subjects who complete the study; and defined as (date of withdrawal - first infusion date + 1) for subjects who withdraw from the study.
Time frame: One year
Population: Intent-to-Treat (ITT) Population: Defined as of all subjects who were enrolled into the study and received any amount of the IMP. This population was used for display of demographics, disposition, and for the primary safety and efficacy analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 28-day Schedule | The Number of Days of Oral Therapeutic Antibiotics | 13.3 Days | Standard Deviation 24.5 |
| 21-day Schedule | The Number of Days of Oral Therapeutic Antibiotics | 13.1 Days | Standard Deviation 18.38 |
| Total | The Number of Days of Oral Therapeutic Antibiotics | 13.2 Days | Standard Deviation 22.09 |
Secondary
The Number of Days of Unscheduled Physician Visits Due to Infections
Based on the total number of days of unscheduled physician visits due to infections for each subject. Mean and SD are calculated based on weighting for the duration of data available for each subject, where duration is defined as (date of last visit - first infusion date + 1) for subjects who complete the study; and defined as (date of withdrawal - first infusion date + 1) for subjects who withdraw from the study.
Time frame: One year
Population: Intent-to-Treat (ITT) Population: Defined as of all subjects who were enrolled into the study and received any amount of the IMP. This population was used for display of demographics, disposition, and for the primary safety and efficacy analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 28-day Schedule | The Number of Days of Unscheduled Physician Visits Due to Infections | 2.3 Days | Standard Deviation 4.56 |
| 21-day Schedule | The Number of Days of Unscheduled Physician Visits Due to Infections | 2.4 Days | Standard Deviation 2.25 |
| Total | The Number of Days of Unscheduled Physician Visits Due to Infections | 2.3 Days | Standard Deviation 3.75 |