A Study of NewGam, Human Immunoglobulin 10%, in Patients With Primary Immunodeficiency Diseases

Study Overview
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Brief Summary
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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
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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.

Official Title
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Clinical Study to Evaluate the Efficacy, Pharmacokinetics and Safety of Immunoglobulin Intravenous (Human) 10% (NewGam) in Patients With Primary Immunodeficiency Diseases

Conditions
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Primary Immunodeficiency Diseases

Intervention / Treatment
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* Biological: NewGam


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NewGam<br>Participants received NewGam 200-800 mg/kg intravenously every 3 weeks (17 infusions) or 4 weeks (13 infusions) for 1 year. | Biological: NewGam<br>* 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.<br>* Other names: Human normal immunoglobulin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline to end of the study (up to 12 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IgG Trough Level Concentration | Total IgG trough concentrations were measured in serum samples taken before each infusion. | Baseline to end of the study (up to 12 months) | 
| 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. | Baseline to end of the study (up to 12 months) | 
| 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. | Baseline to end of the study (up to 12 months) | 
| 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. | Baseline to end of the study (up to 12 months) | 
| 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. | Baseline to end of the study (up to 12 months) | 
| 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. | Baseline to end of the study (up to 12 months) | 
| 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. | Baseline to end of the study (up to 12 months) | 
| 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. | Baseline to end of the study (up to 12 months) | 
| 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. | Baseline to end of the study (up to 12 months) | 
| 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. | Baseline to end of the study (up to 12 months) | 
| 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. | Baseline to end of the study (up to 12 months) | 
| 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. | Baseline to end of the study (up to 12 months) | 
| 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. | Baseline to end of the study (up to 12 months) | 
| Number of Participants Hospitalized Due to an Infection |  | Baseline to end of the study (up to 12 months) | 
| Percentage of Participants With at Least 1 Episode of Fever |  | Baseline to end of the study (up to 12 months) | 
| Percentage of Participants That Missed School or Work Due to an Infection |  | Baseline to end of the study (up to 12 months) | 
| 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. | Baseline to end of the study (up to 12 months) | 
| 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. | Baseline to end of the study (up to 12 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PID