MedPath

Gammagard Liquid and rHuPH20 in PID

Phase 3
Completed
Conditions
Primary Immunodeficiency Diseases (PID)
Interventions
Biological: Recombinant human hyaluronidase (rHuPH20)+ immune globulin intravenous (IGIV)
Registration Number
NCT00814320
Lead Sponsor
Baxalta now part of Shire
Brief Summary

The purpose of the study is to develop a subcutaneous treatment option for participants with Primary Immunodeficiency Diseases (PID) that allows an administration of Immune Globulin Intravenous (Human), 10% at the same frequency as IV administration.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
89
Inclusion Criteria
  • Participant is 2 years or older at the time of screening
  • Written informed consent obtained from either the participant or the participant's legally acceptable representative prior to any study-related procedures and study product administration
  • Participant has been diagnosed with a PID disorder requiring antibody replacement as defined by WHO criteria
  • Participant has completed or is about to complete Baxter Clinical Study Protocol No. 160601 or has been receiving a regular IGIV-treatment at mean intervals of 21 ± 3 days or 28 ± 3 days, or SC at mean intervals of 5 to 16 days, over a period of at least 3 months prior to enrollment at a minimum dose of 300 mg/kg BW/4 weeks
  • Participant has a serum trough level of IgG > 4.5 g/L at the last documented determination
  • If female of childbearing potential, participant presents with a negative urine pregnancy test and agrees to employ adequate birth control measures for the duration of the study
  • Participant is willing and able to comply with the requirements of the protocol
Read More
Exclusion Criteria
  • Participant has a known history of or is positive at enrollment or screening for one or more of the following: Hepatitis B surface antigen (HbsAg), polymerase chain reaction (PCR) for Hepatitis C Virus (HCV), PCR for Human immunodeficiency virus (HIV) Type 1/2
  • Participant has levels of alanine aminotransferase (ALT) or aspartate amino transferase (AST) > 2.5 times the upper limit of normal for the testing laboratory
  • Participant has persistent severe neutropenia (defined as an absolute neutrophil count [ANC] <= 500/mm3)
  • Participant has creatinine clearance (CLcr) values, calculated according to the formula below, which are < 60% of normal for age and gender for males: CLcr = [(140 - Age(years)) * (body weight (kg))] / [72 * (serum creatinine (mg/dL))] for females: CLcr = [(140 - Age(years)) * (body weight(kg)) * 0.85] / [72 * (serum creatinine (mg/dL))]
  • Participant has been diagnosed with, or has a malignancy (other than adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) within the last 12 months prior to enrollment; participants treated with immunosuppressive chemotherapeutic agents during this period are excluded
  • Participant has a history of thrombotic episodes (including deep vein thrombosis, myocardial infarction, cerebrovascular accident, pulmonary embolism) within the last 12 months
  • Participant has abnormal protein loss (protein losing enteropathy, nephrotic syndrome)
  • Participant has anemia that would preclude phlebotomy for laboratory studies
  • Participant has received any blood or blood product other than an IGIV, SC immunoglobulin, immune serum globulin (ISG) preparation, or albumin within the 6 months prior to enrollment
  • Participant has an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IGIV, SC immunoglobulin, and/or ISG infusions
  • Participant has immunoglobulin A (IgA) deficiency and known anti IgA antibodies
  • Participant is on preventative (prophylactic) antibiotics and cannot stop antibiotics at the time of enrollment
  • Participant has active infection who started on antibiotic therapy for the treatment of infection within 7 days prior to screening
  • Participant has a bleeding disorder or is on anti-coagulation therapy that results in a platelet count less than 20,000/μL or International Normalized Ration (INR) > 2X control, or who, in the opinion of the investigator would be at significant risk of increased bleeding or bruising as a result of SC therapy
  • Participant has total protein > 9 g/dL and participants with myeloma, macroglobulinemia (IgM) and paraproteinemia
  • Participant has a known allergy to hyaluronidase
  • If female, participant is pregnant or lactating at the time of study enrollment
  • Participant has participated in another clinical study involving an investigational product (IP) or device within 30 days prior to study enrollment or is scheduled to participate in another clinical study involving an IP or device during the course of this study; exception: Baxter Study No. 160601
  • Severe dermatitis that would preclude adequate sites for safe product administration
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1Recombinant human hyaluronidase (rHuPH20)+ immune globulin intravenous (IGIV)Efficacy and tolerability of subcutaneous (SC) infusions of immune globulin intravenous (IGIV), 10% with hyaluronidase (rHuPH20) after ramp-up
2Recombinant human hyaluronidase (rHuPH20)+ immune globulin intravenous (IGIV)Pharmacokinetics of intravenous (IV) infusions of immune globulin intravenous (IGIV), 10% and efficacy and tolerability of subcutaneous (SC) infusions of immune globulin intravenous (IGIV), 10% with hyaluronidase (rHuPH20) after ramp-up
Primary Outcome Measures
NameTimeMethod
Validated Acute Serious Bacterial Infection (VASBI) RateThroughout the study period (17 months)

Serious acute bacterial infections include bacteremia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess that are caused by a recognized bacterial pathogen. VASBI rate is the mean number of VASBIs per participant per year, recorded for SC Administration of IGIV, 10%, with rHuPH20 after ramp-up, only. The mean number of VASBIs per participant per year and the 99% upper confidence limit for the acute serious bacterial infection rate were calculated using a Poisson model to account for the length of the observation periods per participant.

Secondary Outcome Measures
NameTimeMethod
Bioavailability (AUC) of IgG After Administration of IGIV, 10% Given Via IV or SC With rHuPH20 in Participants ≥12 YearsPK AUC evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval];SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion

Bioavailability expressed as pharmacokinetic (PK) equivalence of immunoglobulin (IgG) in terms of ratio of Area Under the Concentration Curve (AUC)/Week after administration of immune globulin intravenous (IGIV), 10% given via subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) after ramp-up to intravenous (IV) route, i.e. ratio of AUC/week of SC/rHuPH20 versus IV administration of IGIV, 10%. Expressed as a percentage.

Bioavailability (Trough Levels) of IgG After Administration of IGIV, 10% Given Via IV or SC With rHuPH20 in Participants Aged 2 to < 12 YearsIgG trough levels measured at baseline and on day of each 3- or 4-week infusion for infusion for IV and SC (except during ramp-up for SC) and at end of study visit

Bioavailability expressed as pharmacokinetic (PK) equivalence of immunoglobulin (IgG) in terms of trough levels after administration of immune globulin intravenous (IGIV), 10% given via subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) after ramp-up to intravenous (IV) route, i.e. ratio of AUC/week of SC/rHuPH20 versus IV administration of IGIV, 10%. Expressed as a percentage.

Bioavailability (AUC) of IgG After SC Administration of IGIV, 10%, Given With and Without rHuPH20PK: 160603 (IV: before infusion (inf.) #4 [3-week treatment interval] or inf. #3 [4-week treatment interval];SC: before last SC inf.) 1 hour pre-inf. ≤28 days (+/-2 days) post-inf.; 160601- 1 hour pre-inf. (before inf. #8) ≤7 days (+/-1 day) post-inf.

Bioavailability of immunoglobulin (IgG) after subcutaneous (SC) administration of immune globulin intravenous (IGIV), 10%, with and without recombinant human hyaluronidase (rHuPH20) (from current study 160603 and study 160601, respectively), as measured by ratio of AUC of IgG per dose/kg with versus without rHuPH20. Expressed as a percentage. This was analysed for participants in Stratum A , participants in Stratum B and for all participants who received IGIV, 10% via SC administration (Stratum A plus Stratum B): Stratum A: Participants who provided data both on SC with AND without rHuPH20 ie, participants who participated in both studies 160601 and 160603; Stratum B: Participants who provided data on SC with OR without rHuPH20, but not on both (participants who participated in study 160601 OR 160603, but not in both studies).

Annual Rate of All Infections Per ParticipantThroughout the study period (17 months)

Annual rate of all infections per participant after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) after ramp-up. Point estimates and 95% CIs for the annual rates will be calculated using a Poisson model and the same methodology including allowance for over-dispersion as described for the primary endpoint.

Trough Levels of IgG After Administration of IGIV, 10% Given Via IV or SC With rHuPH20IgG trough levels measured at baseline and on day of each 3- or 4-week infusion for IV and SC (except during ramp up for SC) and at end of study visit.

Trough levels of immunoglobulin (IgG) after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) after ramp-up

Trough Levels of IgG Subclasses After Administration of IGIV, 10% Given Via IV or SC With rHuPH20IgG subclasses (1-4) trough levels measured at baseline and on day of each 3- or 4-week infusion for infusion for IV and SC (except during ramp up for SC) and at end of study visit

Trough levels of immunoglobulin (IgG) subclasses after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) after ramp-up by IgG subclasses 1 to 4 at end of IV treatment and end of SC treatment with rHuPH20 IgG subclass 1 (IgG 1) IgG subclass 2 (IgG 2) IgG subclass 3 (IgG 3) IgG subclass 4 (IgG 4)

Antibody Levels to Tetanus (Clostridium Tetani Toxoid)IV: At baseline; SC/rHuPH20: at baseline then at infusion #1 at ramp-up and at infusions #5, 9, 13 (for 3-week treatment interval) and infusions #4, 7, 10 (for 4-week treatment interval), SC: end of SC treatment and at end of study visit

Antibody levels to Tetanus (Clostridium tetani toxoid) after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) at end of IV treatment and end of SC treatment with rHuPH20

IgG Terminal Half Life (T1/2) for Participants Aged 12 Years and OlderPK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.

Terminal half life (T1/2) for immunoglobulin (IgG) after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) for participants aged 12 years and older. Terminal half life is the time it takes for the plasma concentration or the amount of immunoglobulin in the body to be reduced by 50% during the terminal phase

Time to Maximum IgG Concentration (T-max) for Participants Aged 12 Years and OlderPK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.

Time to Maximum Immunoglobulin (IgG) Concentration (T-max) after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) for participants aged 12 years and older

Tetanus Antibody Minimum Plasma Concentration (C_min) for Participants Aged 12 Years and OlderPK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.

Minimal tetanus (clostridium tetani toxoid) antibody concentration after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) for participants aged 12 years and older

Tetanus Antibody Terminal Half Life (T1/2) for Participants Aged 12 Years and OlderPK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.

Terminal half life (T1/2) for tetanus (clostridium tetani toxoid) antibody after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) with recombinant human hyaluronidase (rHuPH20) for participants aged 12 years and older. Terminal half life is the time it takes for the plasma concentration or the amount of tetanus antibody in the body to be reduced by 50% during the terminal phase

H. Influenzae Antibody Area Under the Curve (AUC)/Week for Participants Aged 12 Years and OlderPK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval];SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.

Influenza (haemophilus influenzae) antibody Area under the Curve (AUC) AUC/week after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) for participants aged 12 years and older. The AUC between adjacent infusions was calculated by the trapezoidal rule. Linear interpolation/extrapolation was used to calculate the AUC for the exact duration of the infusion intervals (21 days for 3-week treatment interval or 28 days for 4-week treatment interval).

Antibody Levels to Haemophilus InfluenzaeIV: At baseline; SC/rHuPH20: at baseline then at infusion #1 at ramp-up and at infusions #5, 9, 13 (for 3-week treatment interval) and infusions #4, 7, 10 (for 4-week treatment interval), SC: end of SC treatment and at end of study visit

Antibody levels to Haemophilus influenzae after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) at end of IV treatment and end of SC treatment with rHuPH20

IgG Minimum Plasma Concentration (C_min) for Participants Aged 12 Years and OlderPK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion

Minimal immunoglobulin (IgG) concentration after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) for participants aged 12 years and Older

Antibody Levels to MeaslesIV: At baseline; SC/rHuPH20: at baseline then at infusion #1 at ramp-up and at infusions #5, 9, 13 (for 3-week treatment interval) and infusions #4, 7, 10 (for 4-week treatment interval), SC: end of SC treatment and at end of study visit

Antibody levels to measles after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) at end of IV treatment and end of SC treatment with rHuPH20

Antibody Levels to Hepatitis BIV: At baseline; SC/rHuPH20: at baseline then at infusion #1 at ramp-up and at infusions #5, 9, 13 (for 3-week treatment interval) and infusions #4, 7, 10 (for 4-week treatment interval), SC: end of SC treatment and at end of study visit

Antibody levels to hepatitis B after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) with recombinant human hyaluronidase (rHuPH20) at end of IV treatment and end of SC treatment with rHuPH20

IgG Area Under the Curve (AUC)/Week for Participants Aged 12 Years and OlderPK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval];SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.

Immunoglobulin (IgG) Area under the Curve (AUC) AUC/week after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) for participants aged 12 years and older. The AUC between adjacent infusions was calculated by the trapezoidal rule. Linear interpolation/extrapolation was used to calculate the AUC for the exact duration of the infusion intervals (21 days for 3-week treatment interval or 28 days for 4-week treatment interval).

IgG Clearance (CL) for Participants Aged 12 Years and OlderPK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval];SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.

Immunoglobulin (IgG) Clearance after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) with recombinant human hyaluronidase (rHuPH20) for participants aged 12 years and older. Clearance (CL) is provided after administration of IGIV,10% given via IV route. Apparent Clearance is provided after administration of IGIV, 10% given via SC route with rHuPH20. Clearance and apparent clearance are determined by weight adjusted dose divided by total AUC.

IgG Maximum Plasma Concentration (C_max) for Participants Aged 12 Years and OlderPK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.

Maximum immunoglobulin (IgG) concentration after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) for participants aged 12 years and older

Tetanus Antibody Area Under the Curve (AUC)/Week for Participants Aged 12 Years and OlderPK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval];SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.

Tetanus (clostridium tetani toxoid) antibody Area under the Curve (AUC) AUC/week after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) for participants aged 12 years and older. The AUC between adjacent infusions was calculated by the trapezoidal rule. Linear interpolation/extrapolation was used to calculate the AUC for the exact duration of the infusion intervals (21 days for 3-week treatment interval or 28 days for 4-week treatment interval).

Tetanus Antibody Clearance (CL) for Participants Aged 12 Years and OlderPK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval];SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.

Tetanus (clostridium tetani toxoid) antibody Clearance after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) for participants aged 12 years and older. Clearance (CL) is provided after administration of IGIV,10% given via IV route. Apparent Clearance is provided after administration of IGIV, 10% given via SC route with rHuPH20. Clearance (CL) and apparent clearance are determined by weight adjusted dose divided by total AUC.

Tetanus Antibody Maximum Plasma Concentration (C_max) for Participants Aged 12 Years and OlderPK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.

Maximum tetanus (clostridium tetani toxoid) antibody concentration after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) with recombinant human hyaluronidase (rHuPH20) for participants aged 12 years and older

Time to Maximum Tetanus Antibody Concentration (T-max) for Participants Aged 12 Years and OlderPK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.

Time to Maximum tetanus (clostridium tetani toxoid) antibody Concentration (T-max) after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) for participants aged 12 years and older

H. Influenzae Antibody Minimum Plasma Concentration (C_min) for Participants Aged 12 Years and OlderPK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.

Minimal influenza (haemophilus influenzae) antibody concentration after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) with recombinant human hyaluronidase (rHuPH20) for participants aged 12 years and older

H. Influenzae Antibody Clearance (CL) for Participants Aged 12 Years and OlderPK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval];SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.

Influenza (haemophilus influenzae) antibody Clearance after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) with recombinant human hyaluronidase (rHuPH20) for participants aged 12 years and older. Clearance (CL) is provided after administration of IGIV,10% given via IV route. Apparent Clearance is provided after administration of IGIV, 10% given via SC route with rHuPH20. Clearance (CL) and apparent clearance are determined by weight adjusted dose divided by total AUC.

H. Influenzae Antibody Maximum Plasma Concentration (C_max) for Participants Aged 12 Years and OlderPK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.

Maximal influenza (haemophilus influenzae) antibody concentration after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) for participants aged 12 years and older

Percentage of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Interrupted or Stopped for Tolerability Concerns or for Adverse Events (AEs)Throughout the study period (17 months)

Percentage of infusions for which the infusion rate was reduced and/or the infusion interrupted or stopped during administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) after ramp-up for tolerability concerns or for adverse events (AEs). IV administration of IGIV, 10%: 365 infusions; SC administration of IGIV, 10% with rHuPH20: 1129 infusions

Rate of Temporally Associated AEs Per InfusionDuring infusion or within 72 hours of completion of infusion

Rate of all AEs (including and excluding infections) per infusion that began during administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) after ramp-up (during infusion) or within 72 hours of completion of an infusion ("temporally associated")

Percentage of Participants Reporting ≥1 Temporally Associated AEsDuring infusion or within 72 hours of completion of infusion

Percentage of participants reporting at least 1 AE (including and excluding infections) during administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) after ramp-up (during infusion) or within 72 hours of completion of infusion ("temporally associated")

Percentage of Infusions Resulting in ≥1 Temporally Associated AEsDuring infusion or within 72 hours of completion of infusion

Percentage of infusions resulting in at least 1 AE (including and excluding infections) during administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) after ramp-up (during infusion) or within 72 hours of completion of infusion ("temporally associated")

H. Influenzae Antibody Terminal Half Life (T1/2) for Participants Aged 12 Years and OlderPK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.

Terminal half life (T1/2) for influenza (haemophilus influenzae) antibody after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) for participants aged 12 years and older. Terminal half life is the time it takes for the plasma concentration or the amount of influenza antibody in the body to be reduced by 50% during the terminal phase.

Time to Maximum H. Influenzae Antibody Concentration (T-max) for Participants Aged 12 Years and OlderPK evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval]; SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion.

Time to Maximum influenza (haemophilus influenzae) antibody Concentration (T-max) after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) for participants aged 12 years and older

Rate of Days Off School or WorkMonthly, for up to 17 months

Monthly rate of days off school or work after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) after ramp-up. Point estimates and 95% CIs for the monthly rates were calculated using a Poisson model and the same methodology including allowance for over-dispersion as described for the primary outcome measures. The lengths of the month were defined as average length of the month in the Gregorian calendar, namely (365\*400+100-3)/(400\*12)= 30.436875 days.

Rate of Days on AntibioticsMonthly, for up to 17 months

Monthly rate of days on antibiotics after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) after ramp-up. Point estimates and 95% CIs for the monthly rates were calculated using a Poisson model and the same methodology including allowance for over-dispersion as described for the primary outcome measures. The lengths of the month was defined as average length of the month in the Gregorian calendar, namely (365\*400+100-3)/(400\*12)= 30.436875 days.

Rate of Acute Physician VisitsMonthly, for up to 17 months

Monthly rate of acute physician visits after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) after ramp-up. Point estimates and 95% CIs for the monthly rates will be calculated using a Poisson model and the same methodology including allowance for over-dispersion as described for the primary outcome measures. The lengths of the month will be defined as average length of the month in the Gregorian calendar, namely (365\*400+100-3)/(400\*12)= 30.436875 days.

Rate of Days in HospitalMonthly, for up to 17 months

Monthly rate of days in hospital after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) after ramp-up. Point estimates and 95% CIs for the monthly rates will be calculated using a Poisson model and the same methodology including allowance for over-dispersion as described for the primary outcome measures. The lengths of the month will be defined as average length of the month in the Gregorian calendar, namely (365\*400+100-3)/(400\*12)= 30.436875 days.

Percentage of Participants for Which the Infusion Rate Was Reduced and/or the Infusion Interrupted or Stopped for Tolerability Concerns or for Adverse Events (AEs)Throughout the study period (17 months)

Percentage of participants for which the infusion rate was reduced and/or the infusion interrupted or stopped during administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) after ramp-up for tolerability concerns or for adverse events (AEs). An infusion was deemed as tolerated if there are no serious Adverse Drug Reactions (ADR), no non-serious moderate or severe local ADRs that prevent completion of the infusion and no non-serious moderate or severe systemic ADRs during infusion or within 60 minutes of completion of the infusion.

Percentage of Participants Reporting ≥1 Temporally Associated Moderate or Severe AEsDuring infusion or within 72 hours of completion of infusion

Percentage of participants reporting at least 1 Moderate or Severe AE (including and excluding infections) during administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) after ramp-up (during infusion) or within 72 hours of completion of infusion ("temporally associated")

Percentage of Infusions Resulting in ≥1 Temporally Associated Moderate or Severe AEs Within 72 Hours of Completion of InfusionDuring infusion or within 72 hours of completion of infusion

Percentage of infusions resulting in at least 1 moderate or severe AE (including and excluding infections) during administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) after ramp-up (during infusion) or within 72 hours of completion of infusion ("temporally associated")

Percentage of SC Doses of IGIV, 10% and rHuPH20 Tolerated at 1 Infusion SiteDuring infusion or within 60 minutes of completion of the infusion

Percentage of subcutaneous (SC) doses of immune globulin intravenous (IGIV), 10% and recombinant human hyaluronidase (rHuPH20) tolerated at 1 infusion site. An infusion was deemed as tolerated if there were no serious adverse drug reactions (ADRs), no non-serious moderate or severe local ADRs that prevented completion of the infusion, and no non-serious moderate or severe systemic ADRs during or within 60 minutes of completion of the infusion.

Percentage of Infusions Associated With ≥1 Systemic AE During Infusion or Within 72 Hours of Completion of InfusionDuring infusion or within 72 hours of completion of infusion

Percentage of intravenous (IV) and subcutaneous (SC) infusions associated with ≥1 systemic AE (including and excluding infections) during administration of immune globulin intravenous (IGIV), 10% given via IV or SC route with recombinant human hyaluronidase (rHuPH20) after ramp-up (during infusion) or within 72 hours of completion of infusion

Percentage of Participants With ≥1 Systemic AE (Including and Excluding Infections) During Infusion or Within 72 Hours of Completion of InfusionDuring infusion or within 72 hours of completion of infusion

Percentage of participants with ≥1 systemic AE (including and excluding Infections) during administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) after ramp-up (during infusion) or within 72 hours of completion of infusion

Percentage of Infusions Associated With ≥1 Local AE (Including and Excluding Infections) During Infusion or Within 72 Hours of Completion of InfusionDuring infusion or within 72 hours of completion of infusion

Percentage of IV and SC (with recombinant human hyaluronidase \[rHuPH20\]) infusions associated with ≥1 local AE (including and excluding infections) during administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with rHuPH20 after ramp-up (during infusion) or within 72 hours of completion of infusion

Percentage of Infusions Associated With ≥1 Local AE At Any Time During the StudyAt any time during the study

Percentage of intravenous (IV) and subcutaneous (SC) infusions with recombinant human hyaluronidase (rHuPH20) after ramp-up of immune globulin intravenous (IGIV), 10% associated with ≥1 local AE (including and excluding infections) at any time during the study

Percentage of Participants With ≥1 Local AE During Infusion or Within 72 Hours of Completion of InfusionDuring infusion or within 72 hours of completion of infusion

Percentage of participants With ≥1 local AE (including and excluding Infections) during administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) after ramp-up (during infusion) or within 72 hours of completion of infusion

Percentage of Participants With ≥1 Local AE At Any Time During the StudyDuring infusion or within 72 hours of completion of infusion

Percentage of participants With ≥1 local AE (including and excluding infections) after administration of immune globulin intravenous (IGIV), 10% given via intravenous (IV) or subcutaneous (SC) route with recombinant human hyaluronidase (rHuPH20) after ramp-up at any time during the study

Rate of AEs Determined to be Related to the Study Drug by the Investigator Per ParticipantThroughout the study period (17 months)

Rate of related AEs defined as the total number of AEs determined by the investigator to be related to the study drug (immune globulin intravenous \[IGIV\], 10% or recombinant human hyaluronidase \[rHuPH20\]), that occur at any time during the study divided by the total number of participants

Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity (A-F)Throughout the study period (17 months)

Categories presented as Preferred term-Seriousness, Relatedness, Severity. The following codes are to be used: Seriousness: non-SAE-non-serious AE; SAE-serious AE Relationship: NR-not related to immune globulin (IGIV), 10% and recombinant human hyaluronidase (rHuPH20); RIGIV-related to IGIV, 10%; RrHu-related to rHuPH20; Rboth-related to both IGIV, 10% and rHuPH20 Severity: Mild; Mod (Moderate); Severe Preferred terms abbreviated: ADHD-Attention Deficit/Hyperactivity Disorder BP-Blood Pressure COPD- Chronic Obstructive Pulmonary Disease

Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity Per Infusion (G-M)Throughout the study period (17 months)

Categories presented as Preferred term-Seriousness, Relatedness, Severity. The following codes are to be used: Seriousness: non-SAE-non-serious AE; SAE-serious AE Relationship: NR-not related to immune globulin (IGIV), 10% and recombinant human hyaluronidase (rHuPH20); RIGIV-related to IGIV, 10%; RrHu-related to rHuPH20; Rboth-related to both IGIV, 10% and rHuPH20 Severity: Mild; Mod (Moderate); Severe

Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity Per Participant (A-F)Throughout the study period (17 months)

Categories presented as Preferred term-Seriousness, Relatedness, Severity. The following codes are to be used: Seriousness: non-SAE-non-serious AE; SAE-serious AE Relationship: NR-not related to immune globulin (IGIV), 10% and recombinant human hyaluronidase (rHuPH20); RIGIV-related to IGIV, 10%; RrHu-related to rHuPH20; Rboth-related to both IGIV, 10% and rHuPH20 Severity: Mild; Mod (Moderate); Severe Preferred terms abbreviated: ADHD-Attention Deficit/Hyperactivity Disorder BP-Blood Pressure COPD- Chronic Obstructive Pulmonary Disease

Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity Per Participant (G-M)Throughout the study period (17 months)

Categories presented as Preferred term-Seriousness, Relatedness, Severity. The following codes are to be used: Seriousness: non-SAE-non-serious AE; SAE-serious AE Relationship: NR-not related to immune globulin (IGIV), 10% and recombinant human hyaluronidase (rHuPH20); RIGIV-related to IGIV, 10%; RrHu-related to rHuPH20; Rboth-related to both IGIV, 10% and rHuPH20 Severity: Mild; Mod (Moderate); Severe

Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity Per Participant (N-Z)Throughout the study period (17 months)

Categories presented as Preferred term-Seriousness, Relatedness, Severity. The following codes are to be used: Seriousness: non-SAE-non-serious AE; SAE-serious AE Relationship: NR-not related to immune globulin (IGIV), 10% and recombinant human hyaluronidase (rHuPH20); RIGIV-related to IGIV, 10%; RrHu-related to rHuPH20; Rboth-related to both IGIV, 10% and rHuPH20 Severity: Mild; Mod (Moderate); Severe Preferred terms abbreviated: Resp.-Respiratory WBC - White blood cells

Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity (G-M)Throughout the study period (17 months)

Categories presented as Preferred term-Seriousness, Relatedness, Severity. The following codes are to be used: Seriousness: non-SAE-non-serious AE; SAE-serious AE Relationship: NR-not related to immune globulin (IGIV), 10% and recombinant human hyaluronidase (rHuPH20); RIGIV-related to IGIV, 10%; RrHu-related to rHuPH20; Rboth-related to both IGIV, 10% and rHuPH20 Severity: Mild; Mod (Moderate); Severe

Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity Per Infusion (N-Z)Throughout the study period (17 months)

Categories presented as Preferred term-Seriousness, Relatedness, Severity. The following codes are to be used: Seriousness: non-SAE-non-serious AE; SAE-serious AE Relationship: NR-not related to immune globulin (IGIV), 10% and recombinant human hyaluronidase (rHuPH20); ; RIGIV-related to IGIV, 10%; RrHu-related to rHuPH20; Rboth-related to both IGIV, 10% and rHuPH20 Severity: Mild; Mod (Moderate); Severe Preferred terms abbreviated: Resp.-Respiratory WBC - White blood cells

Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity Per Infusion (A-F)Throughout the study period (17 months)

Categories presented as Preferred term-Seriousness, Relatedness, Severity. The following codes are to be used: Seriousness: non-SAE-non-serious AE; SAE-serious AE Relationship: NR-not related to immune globulin (IGIV), 10% and recombinant human hyaluronidase (rHuPH20); RIGIV-related to IGIV, 10%; RrHu-related to rHuPH20; Rboth-related to both IGIV, 10% and rHuPH20 Severity: Mild; Mod (Moderate); Severe Preferred terms abbreviated: ADHD-Attention Deficit/Hyperactivity Disorder BP-Blood Pressure COPD- Chronic Obstructive Pulmonary Disease

Rate of AEs Determined to be Related to the Study Drug by the Investigator Per InfusionThroughout the study period (17 months)

Rate of related AEs defined as the total number of AEs determined by the investigator to be related to the study drug (immune globulin intravenous \[IGIV\], 10% or recombinant human hyaluronidase \[rHuPH20\]), that occur at any time during the study divided by the total number of infusions

Frequency of Dose Corrections (If IgG Trough Levels <4.5 g/L) for Each Study Epoch (IV and SC/rHuPH20 Treatment)Throughout the study period (17 months)

Frequency of dose corrections based on immune globulin G (IgG) trough levels \<4.5 g/L IgG, if any, for intravenous (IV) (Epoch 1) and subcutaneous with recombinant human hyaluronidase (SC/rHuPH20) after ramp-up (Epoch 2) administration of immune globulin intravenous (IGIV), 10% Defined/calculated as the number of participants requiring dose adjustments divided by the number of participants, for each respective data set.

Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity (N-Z)Throughout the study period (17 months)

Categories presented as Preferred term-Seriousness, Relatedness, Severity. The following codes are to be used: Seriousness: non-SAE-non-serious AE; SAE-serious AE Relationship: NR-not related to immune globulin (IGIV), 10% and recombinant human hyaluronidase (rHuPH20); RIGIV-related to IGIV, 10%; RrHu-related to rHuPH20; Rboth-related to both IGIV, 10% and rHuPH20 Severity: Mild; Mod (Moderate); Severe Preferred terms abbreviated: Resp.-Respiratory WBC - White blood cells

Percentage of Infusions Associated With ≥1 AE Related to Either or Both Study DrugsThroughout the study period (17 months)

Percentage of Infusions Associated With ≥1 AE Related to immune globulin intravenous (IGIV), 10%, \[administered via intravenous (IV) or subcutaneous (SC) route\], recombinant human hyaluronidase (rHuPH20) or both. The percentage of affected infusions is calculated per subject and then summarized by the median of all subjects analysed.

Percentage of Infusions Tolerated With IV and SC Administration at Dose Used in Study Epoch 2 (SC/rHuPH20 Treatment)Throughout the study period (17 months)

Epoch 2: subcutaneous (SC) administration of immune globulin intravenous (IGIV), 10% with recombinant human hyaluronidase (rHuPH20) after ramp-up. Dose used in Epoch 2 (after ramp-up) was 108% of dose used in intravenous (IV) administration of IGIV, 10%. The percentage of affected infusions is calculated per subject and then summarized by the median of all subjects analysed.

Median Rate of AEs Temporally Associated or Related to Study Drug Per InfusionThroughout the study period (17 months)

Temporally associated defined as during infusion or within 72 hours of completion of infusion. Related defined as determined by investigator to be at least possibly related to study drug (immune globulin intravenous \[IGIV\], 10% or recombinant human hyaluronidase \[rHuPH20\]). Expressed as a percentage.

Number of Participants Who Developed Neutralizing Antibodies to Recombinant Human Hyaluronidase (rHuPH20)Throughout the study period (17 months)
Percentage of Participants Who Developed Neutralizing Antibodies to Recombinant Human Hyaluronidase (rHuPH20)Throughout the study period (17 months)
Number of Participants Who Experienced a Hemoglobin Drop of >2.0 g/dL, With Evidence of Hemolysis on Further AnalysisThroughout the study period (17 months)

Further analysis for incidences of potential hemolysis included direct Coombs' test, free hemoglobin, serum haptoglobin, LDH, urine hemosiderin and microscopic urinalysis

Percentage of Participants Who Experienced a Hemoglobin Drop of >2.0 g/dL, With Evidence of Hemolysis on Further AnalysisThroughout the study period (17 months)

Further analysis for incidences of potential hemolysis included direct Coombs' test, free hemoglobin, serum haptoglobin, LDH, urine hemosiderin and microscopic urinalysis

© Copyright 2025. All Rights Reserved by MedPath
HomeTerms & ConditionsPrivacy Policy