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CompletedNCT02783482Updated Dec 9, 2022Results posted

Study of Immune Globulin Intravenous (Human) GC5107 in Subjects With Primary Humoral Immunodeficiency

A Phase 3 interventional study of GC5107 in Immunologic Deficiency Syndromes, sponsored by Green Cross Corporation. Completed at 20 sites in 2 countries. Open to participants aged 2 Years to 70 Years. Per ClinicalTrials.gov, last updated 2022-12-09.

Sponsored by Green Cross Corporation · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
49
Allocation
Not applicable
Ages
2 Years to 70 Years
Sex
All
01

Study 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).

Read the 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.

02

Conditions studied

  • Immunologic Deficiency Syndromes
03

Who can participate

Ages eligible
2 Years to 70 Years
Sexes eligible
All
Accepts 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

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
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
49 participants (actual)

Study arms

  • Experimental
    GC5107

    GC5107 Immune globulin intravenous (human) solution, 10% liquid

    Biological: GC5107

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)

    Also known as: IGIV, Immune globulin intravenous (human) solution, 10% liquid

05

What researchers measure

Primary outcomes

  1. 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

  2. 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

Secondary outcomes

  1. The Incidence of Infections Other Than Acute Serious Bacterial Infections

    Time frame: One year

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

06

Results

Posted Oct 28, 2022

Participant flow

Participant flow — Overall Study
Milestone28-day Schedule21-day Schedule
Started2920
Completed2419
Not completed51

Outcome measures

PrimaryThe 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
Reported as:
Number · Number of events per patient per year
The Incidence of Acute Serious Bacterial Infections (SBI)
Number of events per patient per year28-day Schedule21-day ScheduleTotal
The Incidence of Acute Serious Bacterial Infections (SBI)0.04 (NA to 0.35)0 (NA to NA)0.02 (NA to 0.21)
PrimaryThe 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
Reported as:
Number · Proportion of infusion with TAAEs
The Proportion of Infusions With Temporally Associated Adverse Events (TAAEs) That Occur Within 72 Hours Following an Infusion of Test Product
Proportion of infusion with TAAEs28-day Schedule21-day ScheduleTotal
The Proportion of Infusions With Temporally Associated Adverse Events (TAAEs) That Occur Within 72 Hours Following an Infusion of Test Product0.31 (NA to 0.40)0.16 (NA to 0.22)0.24 (NA to 0.31)
SecondaryThe Incidence of Infections Other Than Acute Serious Bacterial Infections
Time frame:
One year
Reported as:
Number · Numberof infections per patient per year
The Incidence of Infections Other Than Acute Serious Bacterial Infections
Numberof infections per patient per year28-day Schedule21-day ScheduleTotal
The Incidence of Infections Other Than Acute Serious Bacterial Infections2.43.62.9
SecondaryThe 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
Reported as:
Mean · Days
The Number of Days Missed From Work/School/Kindergarten/Daycare, or Days Unable to Perform Normal Daily Activities Due to Infections
Days28-day Schedule21-day ScheduleTotal
The Number of Days Missed From Work/School/Kindergarten/Daycare, or Days Unable to Perform Normal Daily Activities Due to Infections2.9 ± 4.2012.7 ± 26.117.1 ± 18.04
SecondaryThe 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
Reported as:
Mean · Days
The Number of Days of Unscheduled Physician Visits Due to Infections
Days28-day Schedule21-day ScheduleGC5107 IVIG 10%
The Number of Days of Unscheduled Physician Visits Due to Infections2.3 ± 4.562.4 ± 2.252.3 ± 3.75
SecondaryThe 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
Reported as:
Mean · Days
The Number of Days of Hospitalizations Due to Infections
Days28-day Schedule21-day ScheduleTotal
The Number of Days of Hospitalizations Due to Infections0.1 ± 0.570.1 ± 0.460.1 ± 0.53
SecondaryThe 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
Reported as:
Mean · Days
The Number of Days of Intravenous (IV) Therapeutic Antibiotics
Days28-day Schedule21-day ScheduleGC5107 IVIG 10%
The Number of Days of Intravenous (IV) Therapeutic Antibiotics0.1 ± 0.570.0 ± 0.000.1 ± 0.44
SecondaryThe 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
Reported as:
Mean · Days
The Number of Days of Oral Therapeutic Antibiotics
Days28-day Schedule21-day ScheduleGC5107 IVIG 10%
The Number of Days of Oral Therapeutic Antibiotics13.3 ± 24.5013.1 ± 18.3813.2 ± 22.09

Adverse events

Collected over One year. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
GC5107 IVIG 10%0/49 (0%)4/49 (8.2%)49/49 (100%)
Most frequent serious events
Most frequent serious events
EventGC5107 IVIG 10%
InfluenzaInfections and infestations1/49
Acute urticariaSkin and subcutaneous tissue disorders1/49
ST elevation myocardial infarctionCardiac disorders1/49
Bacterial pneumoniaInfections and infestations1/49
Squamous cell carcinoma of base of tongueNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/49
Most frequent other events
Showing 10 of 42
Most frequent other events
EventGC5107 IVIG 10%
HeadacheNervous system disorders28/49
NauseaGastrointestinal disorders20/49
CoughRespiratory, thoracic and mediastinal disorders15/49
FatigueGeneral disorders13/49
PyrexiaGeneral disorders13/49
SinusitisInfections and infestations13/49
Oropharyngeal painRespiratory, thoracic and mediastinal disorders11/49
DiarrhoeaGastrointestinal disorders9/49
Nasal congestionRespiratory, thoracic and mediastinal disorders9/49
Abdominal pain upperGastrointestinal disorders8/49

Baseline characteristics

Age, Continuous
Age, Continuous(years)28-day Infusion21-day InfusionTotal
Mean41.5 ± 21.730.7 ± 23.237.1 ± 22.7
Sex: Female, Male
Sex: Female, Male(Participants)28-day Infusion21-day InfusionTotal
Female13821
Male161228
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)28-day Infusion21-day InfusionTotal
White281947
Other112
Region of Enrollment
Region of Enrollment(Participants)28-day Infusion21-day InfusionTotal
Canada11213
United States181836
Duration since first IVIG infusion
Duration since first IVIG infusion(years)28-day Infusion21-day InfusionTotal
Mean8.8 ± 8.38.8 ± 6.78.8 ± 7.6
IVIG dose prior to enrollment
IVIG dose prior to enrollment(mg/kg)28-day Infusion21-day InfusionTotal
Mean501.2 ± 94.0592.7 ± 135.9538.5 ± 120.6
07

Study locations

20 sites
  • Immuno International Research Centers
    Centennial, Colorado 80112, United States
  • Allergy Associates of Palm Beaches PA
    North Palm Beach, Florida 33408, United States
  • Midwest Immunology Clinic and Infusion Center
    Plymouth, Minnesota 55446, United States
  • Optimed Infusions LLC
    Columbus, Ohio 43235, United States
  • Oklahoma Institute of Allergy Ashma and Immunology
    Oklahoma City, Oklahoma 73131, United States
  • Allergy Partners of North Texas Research
    Dallas, Texas 75230, United States
  • Allergy and Asthma Specialists
    Dallas, Texas 75231, United States
  • Pediatric Pulmonary Associates of North Texas
    Frisco, Texas 75034, United States
  • Allergy Asthma and Immunology Clinic PA
    Irving, Texas 75063, United States
  • Lysosomal Rare Disorder Research and Treatment Center, Inc.
    Fairfax, Virginia 22030, United States
  • University of Alberta Hospital
    Edmonton, Alberta T6G 2V2, Canada
  • Hamilton Health Sciences Corporation
    Hamilton, Ontario L8S4K1, Canada
  • Queen's University - Kingston General Hospital (KGH)
    Kingston, Ontario K7L 2V7, Canada
  • The Ottawa Hospital
    Ottawa, Ontario K1H 8L6, Canada
  • Gordon Sussman Clinical Research
    Toronto, Ontario M4V 1R2, Canada
  • Saint Michael's Hospital
    Toronto, Ontario M5B 1W8, Canada
  • CHU Ste-Justine - University of Montreal
    Montreal, Quebec H3T 1C5, Canada
  • McGill University Health Centre (MUHC) - The Montreal Children's Hospital
    Montreal, Quebec H4A 3J1, Canada
  • Hotel Dieu de Montreal
    Montréal, Quebec H2W 1T8, Canada
  • Clinique Spécialisée en Allergie de la Capitale
    Québec City, Quebec G1V 4W2, Canada
08

References and documents

Publications

  • Perez EE, Hebert J, Ellis AK, Alpan O, Lumry WR, Shapiro R, Suez D, Mandujano JF, Wasserman RL. Efficacy, Safety and Tolerability of a New 10% Intravenous Immunoglobulin for the Treatment of Primary Immunodeficiencies. Front Immunol. 2021 Jul 8;12:707463. doi: 10.3389/fimmu.2021.707463. eCollection 2021. PubMed 34305948 ↗

Study documents

  • Study protocol · Jan 4, 2019
  • Statistical analysis plan · Nov 5, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT02783482
Lead sponsor
Green Cross Corporation
Collaborators
Parexel, Atlantic Research Group
Responsible party
Sponsor
First posted
May 26, 2016
Start date
Oct 2016
Primary completion
Jul 2019
Completion
Jul 2019
Results posted
Oct 28, 2022
Last update
Dec 9, 2022

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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