Back to resultsA Study of NewGam, Human Immunoglobulin 10%, in Patients With Primary Immunodeficiency Diseases
Primary Purpose
Primary Immunodeficiency Diseases
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
NewGam
Sponsored by
About this trial
This is an interventional treatment trial for Primary Immunodeficiency Diseases focused on measuring PID
Eligibility Criteria
Inclusion Criteria:
- Age of ≥ 2 years and ≤ 75 years.
- Confirmed diagnosis of common variable immunodeficiency (CVID) or X-linked agammaglobulinemia (XLA).
- Previously treated with a commercial immune globulin intravenous (human) every 21-28 days for at least 6 infusion intervals at a constant dose between 200 and 800 mg/kg body weight.
Exclusion Criteria:
- Acute infection requiring intravenous antibiotic treatment within 2 weeks prior to and during the screening period.
- Exposure to blood or any blood product or derivative, other than commercially available intravenous immunoglobulin (IVIG), within the past 3 months prior to enrollment.
- Ongoing history of hypersensitivity or persistent reactions to blood or plasma derived products, or any component of the investigational product.
- Requirement of any routine pre-medication for IVIG infusion.
- Severe liver function impairment (alanine aminotransferase [ALAT] 3x > upper limit of normal).
- Presence of renal function impairment (creatinine > 120 μmol/L), or predisposition for acute renal failure (eg, any degree of pre-existing renal insufficiency or routine treatment with known nephritic drugs).
- History of autoimmune hemolytic anemia.
- History of diabetes mellitus.
- Congestive heart failure New York Heart Association (NYHA) class III or IV.
- Non-controlled arterial hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure > 90 mmHg).
- History of deep vein thrombosis or thrombotic complications of IVIG therapy.
- A positive result at screening on any of the following viral markers: human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV).
- Treatment with steroids (oral or parenteral, long-term, ie, 30 days or more, not intermittent or burst, daily, ≥ 0.15 mg of prednisone or equivalent/kg/day), immunosuppressive or immunomodulatory drugs.
- Planned vaccination during the study period.
- Treatment with any investigational agent within 3 months prior to enrollment.
- Known or suspected to abuse alcohol, drugs, psychotropic agents or other chemicals within the past 12 months prior to enrollment.
- Pregnant or nursing women.
Sites / Locations
- Sudir Gupta, MD
- Isaac Melamed, MD
- James Moy, MD
- William Smits, MD
- Dr. Alan Knutsen
- Ai Lan Kobayashi, MD
- Hans Ochs, MD
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
NewGam
Arm Description
Participants received NewGam 200-800 mg/kg intravenously every 3 weeks (17 infusions) or 4 weeks (13 infusions) for 1 year.
Outcomes
Primary Outcome Measures
Number of Serious Bacterial Infections Per Person-year of Treatment
The number of serious bacterial infections per person-year of treatment was calculated by the following formula: Total number of serious bacterial infections / patient-years on NewGam treatment. Serious bacterial infections were defined as bacteraemia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess.
Secondary Outcome Measures
IgG Trough Level Concentration
Total IgG trough concentrations were measured in serum samples taken before each infusion.
Trough Level Concentration of Antibodies Against Haemophilus Influenzae
Trough level concentrations of antibodies against Haemophilus influenzae were measured in serum blood samples collected before the 1st infusion in all participants, before the 9th and 10th infusions in participants receiving NewGam every 3 weeks, before the 7th and 8th infusions in participants receiving NewGam every 4 weeks, and at the termination visit for all participants.
Trough Level Concentration of Antibodies Against Measles
Trough level concentrations of antibodies against measles were measured in serum blood samples collected before the 1st infusion in all participants, before the 9th and 10th infusions in participants receiving NewGam every 3 weeks, before the 7th and 8th infusions in participants receiving NewGam every 4 weeks, and at the termination visit for all participants.
Trough Level Concentration of Antibodies Against Streptococcus Pneumoniae
Trough level concentrations of antibodies against Streptococcus pneumoniae (serotypes types 6B, 14, 9V, 18C, 19F, 4, and 23F) were measured in serum blood samples collected before the 1st infusion in all participants, before the 9th and 10th infusions in participants receiving NewGam every 3 weeks, before the 7th and 8th infusions in participants receiving NewGam every 4 weeks, and at the termination visit for all participants.
Trough Level Concentration of Antibodies Against Cytomegalovirus
Trough level concentrations of antibodies against cytomegalovirus were measured in serum blood samples collected before the 1st infusion in all participants, before the 9th and 10th infusions in participants receiving NewGam every 3 weeks, before the 7th and 8th infusions in participants receiving NewGam every 4 weeks, and at the termination visit for all participants.
Trough Level Concentration of Antibodies Against Tetanus
Trough level concentrations of antibodies against tetanus were measured in serum blood samples collected before the 1st infusion in all participants, before the 9th and 10th infusions in participants receiving NewGam every 3 weeks, before the 7th and 8th infusions in participants receiving NewGam every 4 weeks, and at the termination visit for all participants.
Trough Level Concentration of Antibodies Against Varicella-zoster Virus
Trough level concentrations of antibodies against varicella-zoster virus were measured in serum blood samples collected before the 1st infusion in all participants, before the 9th and 10th infusions in participants receiving NewGam every 3 weeks, before the 7th and 8th infusions in participants receiving NewGam every 4 weeks, and at the termination visit for all participants.
Total Number of Infections
The number of infections included serious bacterial infections (bacterial pneumonia, bacteraemia/sepsis, osteomyelitis/septic arthritis, visceral abscess, bacterial meningitis) and other infections. For other infections, the Medical Dictionary for Regulatory Activities (MedDRA) preferred term was used to determine the type of infection. They were grouped into the following categories as determined by a medical expert: Ear infections, eye infections, infections of the gastrointestinal tract, infections of the genitourinary tract, upper respiratory tract infections, lower respiratory tract infections, infections of the skin, and infections not elsewhere classified.
Number of Non-serious Infections
The MedDRA preferred term was used to determine the type of non-serious infection. They were grouped into the following categories as determined by a medical expert: Ear infections, eye infections, infections of the gastrointestinal tract, infections of the genitourinary tract, upper respiratory tract infections, lower respiratory tract infections, infections of the skin, and infections not elsewhere classified. The total number of infections and the number in each category are reported.
Time to Resolution of Serious and Other Infections
Since infections were reported as adverse events, the time to resolution of an infection was the time from the start date of the infection adverse event to the end date of the infection adverse event.
Percentage of Participants Treated With Antibiotics
The total percentage of participants treated with antibiotics, as well as, the percentage of participants treated with antibiotics therapeutically and prophylactically are reported.
Number of Antibiotic Treatment Episodes Per Person-year of Treatment
The number of antibiotic treatment episodes per person-year of treatment was calculated by the following formula: Total number of antibiotic treatment episodes / patient-years of NewGam treatment.
Number of Antibiotic Treatment Days Per Person-year of Treatment
The number of antibiotic treatment days per person-year of treatment was calculated by the following formula: Total number of antibiotic treatment days / patient-years of NewGam treatment.
Number of Participants Hospitalized Due to an Infection
Percentage of Participants With at Least 1 Episode of Fever
Percentage of Participants That Missed School or Work Due to an Infection
Changes in the Physical and Psychosocial Child Health Questionnaire-Parent Form Scores From Baseline to the End of the Study
The Quality of Life (QoL) questionnaire Child Health Questionnaire-Parent Form (CHQ-PF50) was completed by a parent or guardian in study participants < 14 years of age. The CHQ-PF50 consists of 50 items organized into 15 subscales.The 15 subscales could be combined into 2 summary scores, physical and psychosocial. The calculated summary scores were transformed to a range of 0-100, where a higher score indicates more positive functioning or better health status. A positive change score indicates improvement.
Changes in the Physical and Mental Short Form-36 Health Survey Scores From Baseline to the End of the Study
The Quality of Life (QoL) questionnaire Short Form-36 Health Survey (SF-36-HS) was completed by participants ≥ 14 years of age. The SF-36-HS consists of 36 items organized into 8 subscales. The 8 subscales could be combined into 2 summary scores, physical and mental. The calculated summary scores were transformed to a range of 0-100, where a higher score indicates better health. A positive change score indicates improvement.
Full Information
NCT ID
NCT01012323
First Posted
November 11, 2009
Last Updated
February 8, 2017
Sponsor
Octapharma
Collaborators
Premier Research Group plc
1. Study Identification
Unique Protocol Identification Number
NCT01012323
Brief Title
A Study of NewGam, Human Immunoglobulin 10%, in Patients With Primary Immunodeficiency Diseases
Official Title
Clinical Study to Evaluate the Efficacy, Pharmacokinetics and Safety of Immunoglobulin Intravenous (Human) 10% (NewGam) in Patients With Primary Immunodeficiency Diseases
Study Type
Interventional
2. Study Status
Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
January 2010 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
June 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Octapharma
Collaborators
Premier Research Group plc
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study was to determine the efficacy of NewGam in preventing serious bacterial infections and to determine the pharmacokinetic profile of NewGam. The safety of NewGam and its effect on quality of life were also evaluated.
Detailed Description
NewGam is a new 10% human normal immunoglobulin (IVIG) solution developed by Octapharma for intravenous administration. It is supplied as a liquid formulation ready to use. The primary therapeutic use of immunoglobulins is to provide antibodies to prevent viral and bacterial diseases (replacement therapy). IVIG has proved to be useful in a variety of clinical conditions other than for replacement of immunoglobulins; IVIG exhibits an immunomodulatory effect. Children and adults with a Primary Immunodeficiency Disease (PID) have an increased risk of recurrent bacterial and viral infections that typically attack the respiratory tract (sinusitis, bronchitis, pneumonia) but can also affect the gastrointestinal tract (gastroenteritis). Theses diseases can be severe and can lead to substantial morbidity. Responses to antibacterial therapy are often poor. At present, most primary immune deficiencies are not curable, but IVIGs have been shown to decrease the total number of severe infections and the duration of hospitalization.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Immunodeficiency Diseases
Keywords
PID
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
51 (Actual)
8. Arms, Groups, and Interventions
Arm Title
NewGam
Arm Type
Experimental
Arm Description
Participants received NewGam 200-800 mg/kg intravenously every 3 weeks (17 infusions) or 4 weeks (13 infusions) for 1 year.
Intervention Type
Biological
Intervention Name(s)
NewGam
Other Intervention Name(s)
Human normal immunoglobulin
Intervention Description
The dose of NewGam, solvent/detergent treated human normal immunoglobulin 10%, remained the same throughout the study, as long as minimum trough levels of serum immunoglobulin G (IgG) was above 5 g/L. If serum IgG trough levels dropped to 5 g/L or less, the dose was to be adjusted at the investigator's discretion. NewGam was supplied as a solution for infusion.
Primary Outcome Measure Information:
Title
Number of Serious Bacterial Infections Per Person-year of Treatment
Description
The number of serious bacterial infections per person-year of treatment was calculated by the following formula: Total number of serious bacterial infections / patient-years on NewGam treatment. Serious bacterial infections were defined as bacteraemia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess.
Time Frame
Baseline to end of the study (up to 12 months)
Secondary Outcome Measure Information:
Title
IgG Trough Level Concentration
Description
Total IgG trough concentrations were measured in serum samples taken before each infusion.
Time Frame
Baseline to end of the study (up to 12 months)
Title
Trough Level Concentration of Antibodies Against Haemophilus Influenzae
Description
Trough level concentrations of antibodies against Haemophilus influenzae were measured in serum blood samples collected before the 1st infusion in all participants, before the 9th and 10th infusions in participants receiving NewGam every 3 weeks, before the 7th and 8th infusions in participants receiving NewGam every 4 weeks, and at the termination visit for all participants.
Time Frame
Baseline to end of the study (up to 12 months)
Title
Trough Level Concentration of Antibodies Against Measles
Description
Trough level concentrations of antibodies against measles were measured in serum blood samples collected before the 1st infusion in all participants, before the 9th and 10th infusions in participants receiving NewGam every 3 weeks, before the 7th and 8th infusions in participants receiving NewGam every 4 weeks, and at the termination visit for all participants.
Time Frame
Baseline to end of the study (up to 12 months)
Title
Trough Level Concentration of Antibodies Against Streptococcus Pneumoniae
Description
Trough level concentrations of antibodies against Streptococcus pneumoniae (serotypes types 6B, 14, 9V, 18C, 19F, 4, and 23F) were measured in serum blood samples collected before the 1st infusion in all participants, before the 9th and 10th infusions in participants receiving NewGam every 3 weeks, before the 7th and 8th infusions in participants receiving NewGam every 4 weeks, and at the termination visit for all participants.
Time Frame
Baseline to end of the study (up to 12 months)
Title
Trough Level Concentration of Antibodies Against Cytomegalovirus
Description
Trough level concentrations of antibodies against cytomegalovirus were measured in serum blood samples collected before the 1st infusion in all participants, before the 9th and 10th infusions in participants receiving NewGam every 3 weeks, before the 7th and 8th infusions in participants receiving NewGam every 4 weeks, and at the termination visit for all participants.
Time Frame
Baseline to end of the study (up to 12 months)
Title
Trough Level Concentration of Antibodies Against Tetanus
Description
Trough level concentrations of antibodies against tetanus were measured in serum blood samples collected before the 1st infusion in all participants, before the 9th and 10th infusions in participants receiving NewGam every 3 weeks, before the 7th and 8th infusions in participants receiving NewGam every 4 weeks, and at the termination visit for all participants.
Time Frame
Baseline to end of the study (up to 12 months)
Title
Trough Level Concentration of Antibodies Against Varicella-zoster Virus
Description
Trough level concentrations of antibodies against varicella-zoster virus were measured in serum blood samples collected before the 1st infusion in all participants, before the 9th and 10th infusions in participants receiving NewGam every 3 weeks, before the 7th and 8th infusions in participants receiving NewGam every 4 weeks, and at the termination visit for all participants.
Time Frame
Baseline to end of the study (up to 12 months)
Title
Total Number of Infections
Description
The number of infections included serious bacterial infections (bacterial pneumonia, bacteraemia/sepsis, osteomyelitis/septic arthritis, visceral abscess, bacterial meningitis) and other infections. For other infections, the Medical Dictionary for Regulatory Activities (MedDRA) preferred term was used to determine the type of infection. They were grouped into the following categories as determined by a medical expert: Ear infections, eye infections, infections of the gastrointestinal tract, infections of the genitourinary tract, upper respiratory tract infections, lower respiratory tract infections, infections of the skin, and infections not elsewhere classified.
Time Frame
Baseline to end of the study (up to 12 months)
Title
Number of Non-serious Infections
Description
The MedDRA preferred term was used to determine the type of non-serious infection. They were grouped into the following categories as determined by a medical expert: Ear infections, eye infections, infections of the gastrointestinal tract, infections of the genitourinary tract, upper respiratory tract infections, lower respiratory tract infections, infections of the skin, and infections not elsewhere classified. The total number of infections and the number in each category are reported.
Time Frame
Baseline to end of the study (up to 12 months)
Title
Time to Resolution of Serious and Other Infections
Description
Since infections were reported as adverse events, the time to resolution of an infection was the time from the start date of the infection adverse event to the end date of the infection adverse event.
Time Frame
Baseline to end of the study (up to 12 months)
Title
Percentage of Participants Treated With Antibiotics
Description
The total percentage of participants treated with antibiotics, as well as, the percentage of participants treated with antibiotics therapeutically and prophylactically are reported.
Time Frame
Baseline to end of the study (up to 12 months)
Title
Number of Antibiotic Treatment Episodes Per Person-year of Treatment
Description
The number of antibiotic treatment episodes per person-year of treatment was calculated by the following formula: Total number of antibiotic treatment episodes / patient-years of NewGam treatment.
Time Frame
Baseline to end of the study (up to 12 months)
Title
Number of Antibiotic Treatment Days Per Person-year of Treatment
Description
The number of antibiotic treatment days per person-year of treatment was calculated by the following formula: Total number of antibiotic treatment days / patient-years of NewGam treatment.
Time Frame
Baseline to end of the study (up to 12 months)
Title
Number of Participants Hospitalized Due to an Infection
Time Frame
Baseline to end of the study (up to 12 months)
Title
Percentage of Participants With at Least 1 Episode of Fever
Time Frame
Baseline to end of the study (up to 12 months)
Title
Percentage of Participants That Missed School or Work Due to an Infection
Time Frame
Baseline to end of the study (up to 12 months)
Title
Changes in the Physical and Psychosocial Child Health Questionnaire-Parent Form Scores From Baseline to the End of the Study
Description
The Quality of Life (QoL) questionnaire Child Health Questionnaire-Parent Form (CHQ-PF50) was completed by a parent or guardian in study participants < 14 years of age. The CHQ-PF50 consists of 50 items organized into 15 subscales.The 15 subscales could be combined into 2 summary scores, physical and psychosocial. The calculated summary scores were transformed to a range of 0-100, where a higher score indicates more positive functioning or better health status. A positive change score indicates improvement.
Time Frame
Baseline to end of the study (up to 12 months)
Title
Changes in the Physical and Mental Short Form-36 Health Survey Scores From Baseline to the End of the Study
Description
The Quality of Life (QoL) questionnaire Short Form-36 Health Survey (SF-36-HS) was completed by participants ≥ 14 years of age. The SF-36-HS consists of 36 items organized into 8 subscales. The 8 subscales could be combined into 2 summary scores, physical and mental. The calculated summary scores were transformed to a range of 0-100, where a higher score indicates better health. A positive change score indicates improvement.
Time Frame
Baseline to end of the study (up to 12 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age of ≥ 2 years and ≤ 75 years.
Confirmed diagnosis of common variable immunodeficiency (CVID) or X-linked agammaglobulinemia (XLA).
Previously treated with a commercial immune globulin intravenous (human) every 21-28 days for at least 6 infusion intervals at a constant dose between 200 and 800 mg/kg body weight.
Exclusion Criteria:
Acute infection requiring intravenous antibiotic treatment within 2 weeks prior to and during the screening period.
Exposure to blood or any blood product or derivative, other than commercially available intravenous immunoglobulin (IVIG), within the past 3 months prior to enrollment.
Ongoing history of hypersensitivity or persistent reactions to blood or plasma derived products, or any component of the investigational product.
Requirement of any routine pre-medication for IVIG infusion.
Severe liver function impairment (alanine aminotransferase [ALAT] 3x > upper limit of normal).
Presence of renal function impairment (creatinine > 120 μmol/L), or predisposition for acute renal failure (eg, any degree of pre-existing renal insufficiency or routine treatment with known nephritic drugs).
History of autoimmune hemolytic anemia.
History of diabetes mellitus.
Congestive heart failure New York Heart Association (NYHA) class III or IV.
Non-controlled arterial hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure > 90 mmHg).
History of deep vein thrombosis or thrombotic complications of IVIG therapy.
A positive result at screening on any of the following viral markers: human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV).
Treatment with steroids (oral or parenteral, long-term, ie, 30 days or more, not intermittent or burst, daily, ≥ 0.15 mg of prednisone or equivalent/kg/day), immunosuppressive or immunomodulatory drugs.
Planned vaccination during the study period.
Treatment with any investigational agent within 3 months prior to enrollment.
Known or suspected to abuse alcohol, drugs, psychotropic agents or other chemicals within the past 12 months prior to enrollment.
Pregnant or nursing women.
Facility Information:
Facility Name
Sudir Gupta, MD
City
Irvine
State/Province
California
Country
United States
Facility Name
Isaac Melamed, MD
City
Centennial
State/Province
Colorado
Country
United States
Facility Name
James Moy, MD
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
William Smits, MD
City
Fort Wayne
State/Province
Indiana
Country
United States
Facility Name
Dr. Alan Knutsen
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
Ai Lan Kobayashi, MD
City
Papillion
State/Province
Nebraska
Country
United States
Facility Name
Hans Ochs, MD
City
Seattle
State/Province
Washington
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study of NewGam, Human Immunoglobulin 10%, in Patients With Primary Immunodeficiency Diseases
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