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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01012323

Enrollment

Registered

2009-11-13

Start date

2010-01-31

Completion date

2012-06-30

Last updated

2017-03-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Primary Immunodeficiency Diseases

Keywords

PID

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.

Interventions

BIOLOGICALNewGam

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.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

2 Years to 75 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Number of Serious Bacterial Infections Per Person-year of Treatment	Baseline to end of the study (up to 12 months)	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

Measure	Time frame	Description
Trough Level Concentration of Antibodies Against Haemophilus Influenzae	Baseline to end of the study (up to 12 months)	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	Baseline to end of the study (up to 12 months)	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	Baseline to end of the study (up to 12 months)	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	Baseline to end of the study (up to 12 months)	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	Baseline to end of the study (up to 12 months)	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	Baseline to end of the study (up to 12 months)	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	Baseline to end of the study (up to 12 months)	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	Baseline to end of the study (up to 12 months)	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.
IgG Trough Level Concentration	Baseline to end of the study (up to 12 months)	Total IgG trough concentrations were measured in serum samples taken before each infusion.
Percentage of Participants Treated With Antibiotics	Baseline to end of the study (up to 12 months)	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	Baseline to end of the study (up to 12 months)	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	Baseline to end of the study (up to 12 months)	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	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	Baseline to end of the study (up to 12 months)	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	Baseline to end of the study (up to 12 months)	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 to Resolution of Serious and Other Infections	Baseline to end of the study (up to 12 months)	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
NewGam Participants received NewGam 200-800 mg/kg intravenously every 3 weeks (17 infusions) or 4 weeks (13 infusions) for 1 year.	51
Total	51

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Investigator Judgment	1

Baseline characteristics

Characteristic	NewGam
Age, Continuous	26.8 Years STANDARD_DEVIATION 19.25
Sex: Female, Male Female	18 Participants
Sex: Female, Male Male	33 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	45 / 51
serious Total, serious adverse events	5 / 51

Outcome results

Primary

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.