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Efficacy, Safety and Pharmacokinetics of Gammaplex in Primary Immunodeficiency Diseases.

Primary Purpose

Primary Immunodeficiency, Common Variable Hypogammaglobulinemia, X-linked Hypogammaglobulinemia

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Gammaplex (Intravenous immunoglobulin)
Sponsored by
Bio Products Laboratory
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Immunodeficiency focused on measuring Primary Antibody Deficiency, Common variable hypogammaglobulinemia, X-linked hypogammaglobulinemia, Hypogammaglobulinemia, Immunodeficiency with hyper-IgM, Wiskott-Aldrich Syndrome

Eligibility Criteria

3 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 1. The subject is 3 years of age or older, of either sex, belonging to any ethnic group, and above a minimum weight of 27.5 kg. This weight is based on the amount of blood required for testing. If subject is participating in the PK segment, the minimum weight required is 37 kg. 2. The subject has a primary immunodeficiency disease, which has as a significant component of hypogammaglobulinemia and/or antibody deficiency (e.g. (exempli gratia / for example), common variable immunodeficiency, X-linked and autosomal forms of agammaglobulinemia, hyper-immunoglobulin M (hyper-IgM) syndrome, Wiskott-Aldrich Syndrome). Isolated deficiency of a single IgG subclass, or of specific antibodies without hypogammaglobulinemia per se, does not qualify for inclusion. 3. The subject has been receiving licensed or investigational (Phase III or IIIb) immunoglobulin intravenous (IGIV) replacement therapy at a dose that has not changed by + 50% of the mean dose for at least 3 months before study entry and is between 300 and 800 mg/kg/infusion. The infusion interval must be between 21 and 28 days inclusive. The subject must have maintained a trough level at least 300 mg/dL (milligram per decilitre) above baseline serum IgG levels (defined as before initiation of any gamma globulin treatment for that subject). The trough level must be 600 mg/dL. 4. Trough levels of IgG and dose of IGIV, treatment intervals, and the trade name of the IGIV treatments used for the last 2 consecutive routine (licensed or investigational product) must be documented for each subject before the first infusion in this study can be administered. 5. If a subject is a female of child-bearing potential, she must have a negative result on an Human Chorionic Gonadotrophin (HCG)-based pregnancy test. 6. If a subject is a female who is or becomes sexually active, she must practice contraception by using a method of proven reliability for the duration of the study. 7. The subject is willing to comply with all aspects of the protocol, including blood sampling, for the duration of the study. 8. The subject has signed an informed consent form (if at least 18 years old) or the subject's parent or legal guardian has signed the informed consent form. If appropriate, the subject has signed a child assent form (See Section 12.3). Exclusion Criteria: Subjects will be excluded if any of the following exclusion criteria are met: The subject has a history of any severe anaphylactic reaction to blood or any blood-derived product. The subject is known to be intolerant to any component of GAMMAPLEX, such as sorbitol (i.e.(id est / that is) , intolerance to fructose). The subject has selective immunoglobulin A (IgA) deficiency, history of reaction to products containing IgA, or has a history of antibodies to IgA. Subjects who have completed the study and subjects who have withdrawn cannot participate in the study for a second time. The subject is currently receiving, or has received, any investigational agent, other than an immune serum globulin (ISG) preparation that is being evaluated in a Phase III or IIIb study, within the prior 3 months. The subject has been exposed to blood or any blood product or derivative within the last 6 months, other than a commercially available IGIV or other forms of commercially available and licensed ISG or an ISG product that is in Phase III or IIIb studies. The subject is pregnant or is nursing. The subject is positive for any of the following at screening: Serological test for Human immunodeficiency virus (HIV) 1&2, Hepatitis C virus (HCV), or Hepatitis B surface antigen (HBsAg) Nucleic Acid test (NAT) for HCV NAT for HIV The subject, at screening, has levels greater than 2.5 times the upper limit of normal as defined at the central laboratory of any of the following: Alanine transaminase (ALT) Aspartate transaminase (AST) The subject has a severe renal impairment (defined as serum creatinine greater than 2 times the upper limit of normal or Blood urea nitrogen (BUN) greater than 2.5 times the upper limit of normal for the range of the laboratory doing the analysis); the subject is on dialysis; the subject has a history of acute renal failure. The subject is known to abuse alcohol, opiates, psychotropic agents, or other chemicals or drugs, or has done so within the past 12 months. The subject has a history of deep vein thrombosis (DVT), or thrombotic complications of IGIV therapy. The subject suffers from any acute or chronic medical condition (e.g., renal disease or predisposing conditions for renal disease, coronary artery disease, or protein losing state) that, in the opinion of the investigator, may interfere with the conduct of the study. The subject has an acquired medical condition, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia (Absolute neutrophil count (ANC) < 1000 x 109/L). The subject is receiving the following medication: Immunosuppressive drugs The subject is receiving the following medication: Steroids (long-term daily, >0.15 mg /kg/day of prednisone or prednisolone of equivalent dose of other corticosteroids) The requirement for burst or intermittent courses would not exclude the subject. Immunomodulatory drugs The subject has non-controlled arterial hypertension (systolic blood pressure > 160 mmHg (millimeters of mercury) and/or diastolic blood pressure > 100 mmHg). The subject has anemia (hemoglobin < 10 g/dL) at screening.

Sites / Locations

  • Allergy Associates of the Palm Beaches
  • Family Allergy and Asthma Center PC
  • Rush University Medical Centre, University Consultants in Allergy & Immunology
  • Childrens Hospital at Buffalo, Allergy Division
  • Allergy, Asthma & Immunology Clinic, P.A.
  • UCLA Medical Centre
  • University of Washington School of Medicine, Dept. of Pediatrics

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Gammaplex

Arm Description

Gammaplex

Outcomes

Primary Outcome Measures

Number of Serious, Acute, Bacterial Infections (SABIs) Per Subject Per Year in Subjects With Primary Immunodeficiency Disease.
By assessing the number of serious, acute, bacterial infections per subject per year in subjects with Primary Immunodeficiency disease.

Secondary Outcome Measures

The Pharmacokinetic (PK) Half-Life of Immunoglobulin G (IgG)
Blood samples for PK analysis were obtained and analysed at 10 different time points, i.e. -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days, at an infusion visit following 6 months of treatment.
The Pharmacokinetic (PK) Clearance of Immunoglobulin G (IgG)
Blood samples for PK analysis were obtained and analysed at 10 different time points, i.e. -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days, at an infusion visit following 6 months of treatment.
The Pharmacokinetic (PK) Volume of Distribution (Vz)of Immunoglobulin G (IgG)
Blood samples for PK analysis were obtained and analysed at 10 different time points, i.e. -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days, at an infusion visit following 6 months of treatment.
The Pharmacokinetic (PK) Mean Residence Time (MRT) for Inmuunoglobulin G (IgG)
Blood samples for PK analysis were obtained and analysed at 10 different time points, i.e. -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days, at an infusion visit following 6 months of treatment.

Full Information

First Posted
January 18, 2006
Last Updated
January 23, 2013
Sponsor
Bio Products Laboratory
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1. Study Identification

Unique Protocol Identification Number
NCT00278954
Brief Title
Efficacy, Safety and Pharmacokinetics of Gammaplex in Primary Immunodeficiency Diseases.
Official Title
A Phase III, Multicenter, Open-Label Study To Evaluate The Efficacy, Safety, and Pharmacokinetics of Gammaplex® in Primary Immunodeficiency Diseases
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
January 2006 (undefined)
Primary Completion Date
November 2007 (Actual)
Study Completion Date
November 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bio Products Laboratory

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The main objective of this study is to see if GAMMAPLEX is efficacious with respect to Food and Drug Administration (FDA) minimal requirements (no more than 1 serious, acute, bacterial infection per subject per year) in subjects with Primary Immunodeficiency Diseases (PID). The secondary objectives are to assess the safety and tolerability of GAMMAPLEX and to determine if GAMMAPLEX has a pharmacokinetic (PK) profile comparable with that of intact Immunoglobulin G (IgG) in subjects with PID.
Detailed Description
Primary Efficacy Variable The primary variable is the number of serious, acute, bacterial infections/subject/year, and it will be based on the total of all of the following events as defined by the FDA: bacterial Pneumonia, bacteremia/sepsis, osteomyelitis/septic arthritis, visceral abscess, and bacterial meningitis. Secondary Efficacy Variables Secondary efficacy will be determined by using the following variables: number of days of work/school missed because of infection per subject year; number and days of hospitalizations because of infection per subject year; number of visits to physicians for acute problems and/or number of visits to hospital emergency rooms per subject year; other infections documented by fever or a positive result on a radiograph and/or culture; number of infectious episodes per subject per year; number of days on therapeutic antibiotics.These data will be entered into the subject diary, confirmed by the physician, and entered on the electronic-CRF (e-CRF). Safety Variables. The variables used to assess safety will be the following: adverse events (AEs); vital signs; clinical laboratory tests and Direct Coombs' Test; transmission of viruses; physical examination. Test product, dose/mode of administration, batch number(s): The GAMMAPLEX dose is 300-800 mg/kg/infusion (milligram per killgram per infusion) every 21 or 28 days, intravenously. At least 2 batches will be used in this study and no more than 1 batch in any given infusion. Duration of treatment: The total duration of treatment is 12 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Immunodeficiency, Common Variable Hypogammaglobulinemia, X-linked Hypogammaglobulinemia, Hypogammaglobulinemia, Immunodeficiency With Hyper-IgM, Wiskott-Aldrich Syndrome
Keywords
Primary Antibody Deficiency, Common variable hypogammaglobulinemia, X-linked hypogammaglobulinemia, Hypogammaglobulinemia, Immunodeficiency with hyper-IgM, Wiskott-Aldrich Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Gammaplex
Arm Type
Other
Arm Description
Gammaplex
Intervention Type
Biological
Intervention Name(s)
Gammaplex (Intravenous immunoglobulin)
Intervention Description
GAMMAPLEX 5g/100 mL, dose is 300-800 mg/kg/infusion every 21 or 28 days, intravenously for 12 months.
Primary Outcome Measure Information:
Title
Number of Serious, Acute, Bacterial Infections (SABIs) Per Subject Per Year in Subjects With Primary Immunodeficiency Disease.
Description
By assessing the number of serious, acute, bacterial infections per subject per year in subjects with Primary Immunodeficiency disease.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
The Pharmacokinetic (PK) Half-Life of Immunoglobulin G (IgG)
Description
Blood samples for PK analysis were obtained and analysed at 10 different time points, i.e. -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days, at an infusion visit following 6 months of treatment.
Time Frame
-5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days
Title
The Pharmacokinetic (PK) Clearance of Immunoglobulin G (IgG)
Description
Blood samples for PK analysis were obtained and analysed at 10 different time points, i.e. -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days, at an infusion visit following 6 months of treatment.
Time Frame
-5, 0, 60 min, 24, 48 hrs, 4, 7, 14, 21 and 28 days
Title
The Pharmacokinetic (PK) Volume of Distribution (Vz)of Immunoglobulin G (IgG)
Description
Blood samples for PK analysis were obtained and analysed at 10 different time points, i.e. -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days, at an infusion visit following 6 months of treatment.
Time Frame
-5, 0, 60 min, 24, 48 hrs, 4, 7, 14, 21 and 28 days
Title
The Pharmacokinetic (PK) Mean Residence Time (MRT) for Inmuunoglobulin G (IgG)
Description
Blood samples for PK analysis were obtained and analysed at 10 different time points, i.e. -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days, at an infusion visit following 6 months of treatment.
Time Frame
-5, 0, 60 min, 24, 48 hrs, 4, 7, 14, 21 and 28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 1. The subject is 3 years of age or older, of either sex, belonging to any ethnic group, and above a minimum weight of 27.5 kg. This weight is based on the amount of blood required for testing. If subject is participating in the PK segment, the minimum weight required is 37 kg. 2. The subject has a primary immunodeficiency disease, which has as a significant component of hypogammaglobulinemia and/or antibody deficiency (e.g. (exempli gratia / for example), common variable immunodeficiency, X-linked and autosomal forms of agammaglobulinemia, hyper-immunoglobulin M (hyper-IgM) syndrome, Wiskott-Aldrich Syndrome). Isolated deficiency of a single IgG subclass, or of specific antibodies without hypogammaglobulinemia per se, does not qualify for inclusion. 3. The subject has been receiving licensed or investigational (Phase III or IIIb) immunoglobulin intravenous (IGIV) replacement therapy at a dose that has not changed by + 50% of the mean dose for at least 3 months before study entry and is between 300 and 800 mg/kg/infusion. The infusion interval must be between 21 and 28 days inclusive. The subject must have maintained a trough level at least 300 mg/dL (milligram per decilitre) above baseline serum IgG levels (defined as before initiation of any gamma globulin treatment for that subject). The trough level must be 600 mg/dL. 4. Trough levels of IgG and dose of IGIV, treatment intervals, and the trade name of the IGIV treatments used for the last 2 consecutive routine (licensed or investigational product) must be documented for each subject before the first infusion in this study can be administered. 5. If a subject is a female of child-bearing potential, she must have a negative result on an Human Chorionic Gonadotrophin (HCG)-based pregnancy test. 6. If a subject is a female who is or becomes sexually active, she must practice contraception by using a method of proven reliability for the duration of the study. 7. The subject is willing to comply with all aspects of the protocol, including blood sampling, for the duration of the study. 8. The subject has signed an informed consent form (if at least 18 years old) or the subject's parent or legal guardian has signed the informed consent form. If appropriate, the subject has signed a child assent form (See Section 12.3). Exclusion Criteria: Subjects will be excluded if any of the following exclusion criteria are met: The subject has a history of any severe anaphylactic reaction to blood or any blood-derived product. The subject is known to be intolerant to any component of GAMMAPLEX, such as sorbitol (i.e.(id est / that is) , intolerance to fructose). The subject has selective immunoglobulin A (IgA) deficiency, history of reaction to products containing IgA, or has a history of antibodies to IgA. Subjects who have completed the study and subjects who have withdrawn cannot participate in the study for a second time. The subject is currently receiving, or has received, any investigational agent, other than an immune serum globulin (ISG) preparation that is being evaluated in a Phase III or IIIb study, within the prior 3 months. The subject has been exposed to blood or any blood product or derivative within the last 6 months, other than a commercially available IGIV or other forms of commercially available and licensed ISG or an ISG product that is in Phase III or IIIb studies. The subject is pregnant or is nursing. The subject is positive for any of the following at screening: Serological test for Human immunodeficiency virus (HIV) 1&2, Hepatitis C virus (HCV), or Hepatitis B surface antigen (HBsAg) Nucleic Acid test (NAT) for HCV NAT for HIV The subject, at screening, has levels greater than 2.5 times the upper limit of normal as defined at the central laboratory of any of the following: Alanine transaminase (ALT) Aspartate transaminase (AST) The subject has a severe renal impairment (defined as serum creatinine greater than 2 times the upper limit of normal or Blood urea nitrogen (BUN) greater than 2.5 times the upper limit of normal for the range of the laboratory doing the analysis); the subject is on dialysis; the subject has a history of acute renal failure. The subject is known to abuse alcohol, opiates, psychotropic agents, or other chemicals or drugs, or has done so within the past 12 months. The subject has a history of deep vein thrombosis (DVT), or thrombotic complications of IGIV therapy. The subject suffers from any acute or chronic medical condition (e.g., renal disease or predisposing conditions for renal disease, coronary artery disease, or protein losing state) that, in the opinion of the investigator, may interfere with the conduct of the study. The subject has an acquired medical condition, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia (Absolute neutrophil count (ANC) < 1000 x 109/L). The subject is receiving the following medication: Immunosuppressive drugs The subject is receiving the following medication: Steroids (long-term daily, >0.15 mg /kg/day of prednisone or prednisolone of equivalent dose of other corticosteroids) The requirement for burst or intermittent courses would not exclude the subject. Immunomodulatory drugs The subject has non-controlled arterial hypertension (systolic blood pressure > 160 mmHg (millimeters of mercury) and/or diastolic blood pressure > 100 mmHg). The subject has anemia (hemoglobin < 10 g/dL) at screening.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Melvin Berger, MD
Organizational Affiliation
Rainbow Babies & Children's Hospital, Cleveland, Ohio
Official's Role
Principal Investigator
Facility Information:
Facility Name
Allergy Associates of the Palm Beaches
City
North Palm Beach
State/Province
Florida
ZIP/Postal Code
33408
Country
United States
Facility Name
Family Allergy and Asthma Center PC
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Rush University Medical Centre, University Consultants in Allergy & Immunology
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Childrens Hospital at Buffalo, Allergy Division
City
Buffalo
State/Province
New York
ZIP/Postal Code
14222
Country
United States
Facility Name
Allergy, Asthma & Immunology Clinic, P.A.
City
Irving
State/Province
Texas
ZIP/Postal Code
75063
Country
United States
Facility Name
UCLA Medical Centre
City
Irving
State/Province
Texas
ZIP/Postal Code
75063
Country
United States
Facility Name
University of Washington School of Medicine, Dept. of Pediatrics
City
Seattle
State/Province
Washington
ZIP/Postal Code
989109-5235
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.bpl.co.uk
Description
Sponsor website

Learn more about this trial

Efficacy, Safety and Pharmacokinetics of Gammaplex in Primary Immunodeficiency Diseases.

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