Clinical Assessment of Pharmacokinetics, Efficacy, and Safety of 10% IVIg in PID Patients

Incidence rate was defined as the mean number of acute serious bacterial infections (bacterial pneumonia, bacteremia/sepsis, bacterial meningitis, visceral abscess, osteomyelitis/septic arthritis) per participant-year according to pre-specified criteria.

The serum IgG trough levels were collected and analyzed at a central laboratory.

IgG subclasses levels (IgG1, IgG2, IgG3, IgG4) were collected and analyzed at a central laboratory.

Number of participants with Total IgG trough levels <= 6 g/L criteria were reported.

The anti-tetanus toxoid antibody levels were collected and analyzed at a central laboratory. This antibody level was measured in international units per milliliter (IU/mL).

Anti-pneumococcal capsular polysaccharide antibody levels for serotype 1, serotype 12, serotype 14, serotype 17, serotype 19, serotype 2, serotype 20, serotype 22, serotype 23, serotype 26, serotype 3, serotype 4, serotype 34, serotype 43, serotype 5, serotype 51, serotype 54, serotype 56, serotype 57, serotype 68, serotype 70, serotype 8 and serotype 9 were collected and analyzed at a central laboratory.

The anti-measles antibody levels were collected and analyzed at a central laboratory.

The anti-haemophilus influenza type B antibody levels were collected and analyzed at central laboratory.

Incidence rate was defined as the mean number of any infection other than acute serious bacterial infections (bacterial pneumonia, bacteraemia/sepsis, bacterial meningitis, visceral abscess, osteomyelitis/septic arthritis) per participant-year. Incidence rate of any infection other than acute bacterial serious infections collected by the participant/participants parent(s)/legal guardian(s) in the participant diary or during clinic visit was reported.

Duration of any infection other than serious acute bacterial infections (in days) was calculated as date of stop of infection - date of start of infection + 1. Duration of any infection other than serious acute bacterial infections collected by the by the participant/participants parent(s)/legal guardian(s) in the participant diary or during clinic visit was reported.

Incidence rate was defined as the mean number of fever episodes per participant-year. Incidence rate of fever episodes collected by the participant/participant's parent(s)/legal guardian(s) in the participant diary or during clinic visit were reported.

Duration of fever episodes in participants was reported.

Duration of overall participants hospitalization was reported.

Duration of participants hospitalization due to infection was reported.

Incidence rate was defined as the mean number of antibiotics episodes per participant year. Incidence rate of participants on antibiotics for treatment of any kind of infections was reported.

Duration of participants on antibiotics for treatment of any kind of infection was reported.

Duration of missed school/work/other major activities due to infections was reported.

23-item PedsQL generic core scales was a modular approach to measure health-related Quality of Life (QoL) in healthy children, adolescents and those with acute and chronic health conditions. The total scale score (23 items) consisted of Physical Health Summary Score (8 items) and Psychosocial Health SummaryScore (15 items). Physical health summary included Physical Functioning (8 items) and Psychosocial health summary score included Emotional Functioning (5 items), Social Functioning (5 items) and School Functioning (5 items). Items were scored on a 5 point Likert-type response scale: 0=never a problem; 1=almost never a problem; 2=sometimes a problem; 3=often a problem; and 4=almost always a problem). Once scored, items were reverse scored and linearly transformed to a 0-100 scale, where higher scores indicated better QoL. The overall range for total PedsQL score (23 items) was 0 to 100, with higher score indicated better QoL. Data for 18-25 years and >25 years age group was reported.

An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a study drug which may or may not have a causal relationship with the study drug. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life- threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAE was defined as an AE with an onset that occurs after receiving study drug. Any TEAE included participants with both serious and non-serious TEAEs.

An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a study drug which may or may not have a causal relationship with the study drug. A SAE was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life- threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. A TEAE was defined as an AE with an onset that occurs after receiving study drug. Number of TEAEs and Serious TEAEs were reported.

An AE was defined as any untoward medical occurrence in a participant administered a study drug which may or may not have a causal relationship with the study drug. Number of drug related infusion AEs were reported.

Percentage of participants who experienced at least one drug related infusion AEs were reported.

Number of infusions with decreased infusion rate due to AEs were reported.

The number of infusions with one or more infusion associated AEs were reported collectively for 21 and 28-day dosing schedule up to Week 52.

Vital signs included body temperature, systolic and diastolic blood pressure, heart rate and weight. The systolic and diastolic blood pressure and pulse rate was measured after the participants have in a rested at least 3 minutes in seated position. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in vital signs were reported.

Physical examination included the examination of general appearance, skin, neck, eyes, ears, nose, throat, cardiovascular assessment including rhythm, and presence of other cardiac abnormalities (for example gallops, murmurs, cardiomegaly), respiratory system, gastrointestinal system, genitourinary system and musculoskeletal system. Clinical significance was decided by the investigator. The number of participants with clinically significant changes from baseline in physical examination were reported.

Laboratory parameters included chemistry, hematology and urinalysis. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in laboratory parameters were reported.

Intravascular hemolysis testing was performed by using coomb's test. The coomb's assessment was performed at a central laboratory.

Number of participants with positive urine hemosiderin test were reported.

Number of participants with plasma-free haemoglobin level more than or equal to (>=) 69 milligrams per deciliter (mg/dL) were consisdered as abormal and were reported.

Number of participants with abnormal serum haptoglobin level were reported.

Cmax was obtained directly from the concentration versus time curve. Both baseline corrected and un-corrected data was reported.

t1/2 was the time measured for the concentration to decrease by one half. t1/2 was calculated by natural log 2 divided by Kel. Kel was the elimination rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase. Both baseline corrected and un-corrected data was reported.

Area under the serum concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. Both baseline corrected and un-corrected data was reported.

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Kel, where Clast pred was the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above the Lower Limit of quantification (LLOQ) and Kel was the elimination rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase. Both baseline corrected and un-corrected data was reported.

AUCtau was defined as area under the serum concentration-time curve from time zero to the end of the dosing interval (tau). AUCtau was calculated using the mixed log linear trapezoidal rule. Both baseline corrected and un-corrected data was reported.

Vd was defined as the the theoretical volume in which the total amount of total IgG would need to be uniformly distributed to produce the desired blood concentration of a total IgG. Both baseline corrected and un-corrected data was reported.

Clearance of a total IgG was a measure of the rate at which a total IgG is metabolized or eliminated by normal biological processes. CLss of total IgG was measured in milliliters per hour per kilogram (mL/hr/kg). Both baseline corrected and un-corrected data was reported.

Cmin was minimum observed serum concentration obtained directly from the concentration versus time curve. Both baseline corrected and un-corrected data was reported.

Tmax was obtained directly from the concentration versus time curve. Both baseline corrected and un-corrected data was reported.

Kel was the elimination rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase. Both baseline corrected and un-corrected data was reported.

Average concentration of total IgG over the dosing interval (Cavg) was reported. Both baseline corrected and un-corrected data was reported.

The peak trough fluctuation within complete dosing interval at steady state of total IgG was reported. Both baseline corrected and un-corrected data was reported.

Cmax was obtained directly from the concentration versus time curve.

t1/2 was the time measured for the concentration to decrease by one half. t1/2 was calculated by natural log 2 divided by Kel. Kel was the elimination rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase.

Area under the serum concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. The AUC0-t of antigen-specific tetanus toxoid antibodies was measured in hour*international units per milliliter (hr*IU/mL).

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Kel, where Clast pred was the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above the Lower Limit of quantification (LLOQ) and Kel was the elimination rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase.

AUCtau was defined as area under the serum concentration-time curve from time zero to the end of the dosing interval (tau). AUCtau was calculated using the mixed log linear trapezoidal rule.

Vd was defined as the the theoretical volume in which the total amount of antigen-specific tetanus toxoid antibodies would need to be uniformly distributed to produce the desired blood concentration of antigen-specific tetanus toxoid antibodies. The Vd of antigen-specific tetanus toxoid antibodies was measured in milligrams*milliliter per international unit*kilogram (mg*mL/IU*kg).

Clearance of a antigen-specific tetanus toxoid antibodies was a measure of the rate at which a antigen-specific tetanus toxoid antibodies are metabolized or eliminated by normal biological processes. The CLss of antigen-specific tetanus toxoid antibodies was reported. The CLss of antigen-specific tetanus toxoid antibodies was measured in milligrams*milliliter per hour*international unit*kilogram (mg*mL/hr*IU*kg).

Cmin was minimum observed serum concentration obtained directly from the concentration versus time curve.

Tmax was obtained directly from the concentration versus time curve.

Kel was the elimination rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase.

Average concentration of antigen-specific tetanus toxoid antibodies over the dosing interval (Cavg) was reported.

The peak trough fluctuation within complete dosing interval at steady state of antigen-specific tetanus toxoid antibodies was reported.

Cmax was obtained directly from the concentration versus time curve.

t1/2 was the time measured for the concentration to decrease by one half. t1/2 was calculated by natural log 2 divided by Kel. Kel was the elimination rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase.

Area under the serum concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. AUC0-t of antigen-specific haemophilus influenza Type B Antibodies was measured in hour*microgram per milliliter (hr*mcg/mL).

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Kel, where Clast pred was the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above the Lower Limit of quantification (LLOQ) and Kel was the elimination rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase.

AUCtau was defined as area under the serum concentration-time curve from time zero to the end of the dosing interval (tau). AUCtau was calculated using the mixed log linear trapezoidal rule.

Vd was defined as the the theoretical volume in which the total amount of antigen-specific haemophilus influenza type B antibodies would need to be uniformly distributed to produce the desired blood concentration of a antigen-specific haemophilus influenza type B antibodies.

Clearance of antigen-specific haemophilus influenza type B antibodies was a measure of the rate at which antigen-specific haemophilus influenza type B antibodies were metabolized or eliminated by normal biological processes. CLss of antigen-specific haemophilus influenza type B antibodies was measured in milliliter per hour per kilogram (mL/hr/kg).

Cmin was minimum observed serum concentration obtained directly from the concentration versus time curve.

Tmax was obtained directly from the concentration versus time curve.

Terminal Elimination Rate Constant (lambda z) derived if data allowed based on PK acceptance criteria

Average concentration of antigen-specific haemophilus influenza type B antibodies over the dosing interval (Cavg) was reported.

The peak trough fluctuation within complete dosing interval at steady state of antigen-specific haemophilus influenza type B antibodies was reported.

Cmax was obtained directly from the concentration versus time curve. The Cmax for serotype 1, serotype 12, serotype 14, serotype 17, serotype 19, serotype 2, serotype 20, serotype 22, serotype 23, serotype 26, serotype 3, serotype 4, serotype 34, serotype 43, serotype 5, serotype 51, serotype 54, serotype 56, serotype 57, serotype 68, serotype 70, serotype 8, serotype 9 was reported at Week 16 during 28-day dosing schedule and at Week 18 during 21-day dosing schedule.

t1/2 was the time measured for the concentration to decrease by one half. t1/2 was calculated by natural log 2 divided by Kel. Kel was the elimination rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase.Kel was the elimination rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase. The t1/2 for serotype 1, serotype 12, serotype 14, serotype 17, serotype 19, serotype 2, serotype 20, serotype 22, serotype 23, serotype 26, serotype 3, serotype 4, serotype 34, serotype 43, serotype 5, serotype 51, serotype 54, serotype 56, serotype 57, serotype 68, serotype 70, serotype 8 and serotype 9 was reported at Week 16 during 28-day dosing schedule and at Week 18 during 21-day dosing schedule.

Area under the serum concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. AUC0-t of antigen-pneumococcal capsular polysaccharide was measured in hour*microgram per milliliter (hr*mcg/mL). The AUC0-t for serotype 1, serotype 12, serotype 14, serotype 17, serotype 19, serotype 2, serotype 20, serotype 22, serotype 23, serotype 26, serotype 3, serotype 4, serotype 34, serotype 43, serotype 5, serotype 51, serotype 54, serotype 56, serotype 57, serotype 68, serotype 70, serotype 8 and serotype 9 was reported at Week 16 during 28-day dosing schedule and at Week 18 during 21-day dosing schedule.

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Kel, where Clast pred was the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above the Lower Limit of quantification (LLOQ) and Kel was the elimination rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase. The AUC0-inf for serotype 1, serotype 12, serotype 14, serotype 17, serotype 19, serotype 2, serotype 20 serotype 22, serotype 23, serotype 26, serotype 3, serotype 4, serotype 34, serotype 43, serotype 5, serotype 51, serotype 54, serotype 56, serotype 57, serotype 68, serotype 70, serotype 8 and serotype 9 was reported at Week 16 during 28-day dosing schedule and at Week 18 during 21-day dosing schedule.

AUCtau was defined as area under the serum concentration-time curve from time zero to the end of the dosing interval (tau). AUCtau was calculated using the mixed log linear trapezoidal rule. The AUCtau for serotype 1, serotype 12, serotype 14, serotype 17, serotype 19, serotype 2, serotype 20, serotype 22, serotype 23, serotype 26, serotype 3, serotype 4, serotype 34, serotype 43, serotype 5, serotype 51, serotype 54, serotype 56, serotype 57, serotype 68, serotype 70, serotype 8 and serotype 9 was reported at Week 16 during 28-day dosing schedule and at Week 18 during 21-day dosing schedule.

Vd was defined as the the theoretical volume in which the total amount of anti-pneumococcal capsular polysaccharide would need to be uniformly distributed to produce the desired blood concentration of a anti-pneumococcal capsular polysaccharide. The Vd for serotype 1, serotype 12, serotype 14, serotype 17, serotype 19, serotype 2, serotype 20, serotype 22, serotype 23, serotype 26, serotype 3, serotype 4, serotype 34, serotype 43, serotype 5, serotype 51, serotype 54, serotype 56, serotype 57, serotype 68, serotype 70, serotype 8 and serotype 9 was reported at Week 16 during 28-day dosing schedule and at Week 18 during 21-day dosing schedule.

Clearance of a anti-pneumococcal capsular polysaccharide antibodies was a measure of the rate at which a anti-pneumococcal capsular polysaccharide antibodies are metabolized or eliminated by normal biological processes. The CLss of anti-pneumococcal capsular polysaccharide antibodies was reported. The CLss of anti-pneumococcal capsular polysaccharide antibodies was measured in milligrams*milliliter per hour*international unit*kilogram (mg*mL/hr*IU*kg). The CLss for serotype 1, serotype 12, serotype 14, serotype 17, serotype 19, serotype 2, serotype 20, serotype 22, serotype 23, serotype 26, serotype 3, serotype 4, serotype 34, serotype 43, serotype 5, serotype 51, serotype 54, serotype 56, serotype 57, serotype 68, serotype 70, serotype 8 and serotype 9 was reported at Week 16 during 28-day dosing schedule and at Week 18 during 21-day dosing schedule.

Cmin was minimum observed serum concentration obtained directly from the concentration versus time curve. The Cmin for serotype 1, serotype 12, serotype 14, serotype 17, serotype 19, serotype 2, serotype 20, serotype 22, serotype 23, serotype 26, serotype 3, serotype 4, serotype 34, serotype 43, serotype 5, serotype 51, serotype 54, serotype 56, serotype 57, serotype 68, serotype 70, serotype 8 and serotype 9 was reported at Week 16 during 28-day dosing schedule and at Week 18 during 21-day dosing schedule.

Tmax was obtained directly from the concentration versus time curve. The Tmax for serotype 1, serotype 12, serotype 14, serotype 17, serotype 19, serotype 2, serotype 20, serotype 22, serotype 23, serotype 26, serotype 3, serotype 4, serotype 34, serotype 43, serotype 5, serotype 51, serotype 54, serotype 56, serotype 57, serotype 68, serotype 70, serotype 8 and serotype 9 was reported at Week 16 during 28-day dosing schedule and at Week 18 during 21-day dosing schedule.

Kel was the elimination rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase. The Kel for serotype 1, serotype 12, serotype 14, serotype 17, serotype 19, serotype 2, serotype 20 serotype 22, serotype 23, serotype 26, serotype 3, serotype 4, serotype 34, serotype 43, serotype 5, serotype 51, serotype 54, serotype 56, serotype 57, serotype 68, serotype 70, serotype 8 and serotype 9 was reported at Week 16 during 28-day dosing schedule and at Week 18 during 21-day dosing schedule.

Average concentration of anti-pneumococcal capsular polysaccharide over the dosing interval (Cavg) was reported. The Cavg for serotype 1, serotype 12, serotype 14, serotype 17, serotype 19, serotype 2, serotype 20, serotype 22, serotype 23, serotype 26, serotype 3, serotype 4, serotype 34, serotype 43, serotype 5, serotype 51, serotype 54, serotype 56, serotype 57, serotype 68, serotype 70, serotype 8 and serotype 9 was reported at Week 16 during 28-day dosing schedule and at Week 18 during 21-day dosing schedule.

The peak trough fluctuation within complete dosing interval at steady state of anti-pneumococcal capsular polysaccharide was reported. The peak trough fluctuation for serotype 1, serotype 12, serotype 14, serotype 17, serotype 19, serotype 2, serotype 20, serotype 22, serotype 23, serotype 26, serotype 3, serotype 4, serotype 34, serotype 43, serotype 5, serotype 51, serotype 54, serotype 56, serotype 57, serotype 68, serotype 70, serotype 8 and serotype 9 was reported at Week 16 during 28-day dosing schedule and at Week 18 during 21-day dosing schedule.