Gammagard Liquid and rHuPH20 in PID

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00814320
• Date of registration: 23/12/2008
• Prospective Registration: No
• Primary sponsor: Baxalta now part of Shire
• Public title: Gammagard Liquid and rHuPH20 in PID
• Scientific title: Efficacy, Tolerability and Pharmacokinetic Comparison of Immune Globulin Intravenous (Human), 10% (GAMMAGARD LIQUID/KIOVIG) Administered Intravenously or Subcutaneously Following Administration of Recombinant Human Hyaluronidase (rHuPH20) in Subjects With Primary Immunodeficiency Diseases
• Date of first enrolment: December 18, 2008
• Target sample size: 89
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00814320
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Canada, United States

Contacts

• Name: Study Director
• Affiliation: Shire

Key inclusion & exclusion criteria

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

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



Age minimum: 2 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Primary Immunodeficiency Diseases (PID)

Intervention(s)

Biological: Recombinant human hyaluronidase (rHuPH20)+ immune globulin intravenous (IGIV)

Primary Outcome(s)

Validated Acute Serious Bacterial Infection (VASBI) Rate [Time Frame: Throughout the study period (17 months)]

Secondary Outcome(s)

H. Influenzae Antibody Minimum Plasma Concentration (C_min) for Participants Aged 12 Years and Older [Time Frame: PK 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.]

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

Percentage of Infusions Associated With =1 Systemic AE During Infusion or Within 72 Hours of Completion of Infusion [Time Frame: During infusion or within 72 hours of completion of infusion]

Bioavailability (AUC) of IgG After Administration of IGIV, 10% Given Via IV or SC With rHuPH20 in Participants =12 Years [Time Frame: PK 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]

Percentage of Participants Who Developed Neutralizing Antibodies to Recombinant Human Hyaluronidase (rHuPH20) [Time Frame: Throughout the study period (17 months)]

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

Percentage of Participants Who Experienced a Hemoglobin Drop of >2.0 g/dL, With Evidence of Hemolysis on Further Analysis [Time Frame: Throughout the study period (17 months)]

Percentage of Infusions Associated With =1 AE Related to Either or Both Study Drugs [Time Frame: Throughout the study period (17 months)]

Rate of AEs Determined to be Related to the Study Drug by the Investigator Per Infusion [Time Frame: Throughout the study period (17 months)]

Percentage of Participants With =1 Local AE During Infusion or Within 72 Hours of Completion of Infusion [Time Frame: During infusion or within 72 hours of completion of infusion]

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

H. Influenzae Antibody Terminal Half Life (T1/2) for Participants Aged 12 Years and Older [Time Frame: PK 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.]

Antibody Levels to Tetanus (Clostridium Tetani Toxoid) [Time Frame: 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]

Bioavailability (Trough Levels) of IgG After Administration of IGIV, 10% Given Via IV or SC With rHuPH20 in Participants Aged 2 to < 12 Years [Time Frame: IgG 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]

H. Influenzae Antibody Clearance (CL) for Participants Aged 12 Years and Older [Time Frame: PK 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.]

IgG Area Under the Curve (AUC)/Week for Participants Aged 12 Years and Older [Time Frame: PK 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.]

Annual Rate of All Infections Per Participant [Time Frame: Throughout the study period (17 months)]

Antibody Levels to Haemophilus Influenzae [Time Frame: 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]

Time to Maximum IgG Concentration (T-max) for Participants Aged 12 Years and Older [Time Frame: PK 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.]

IgG Clearance (CL) for Participants Aged 12 Years and Older [Time Frame: PK 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.]

Percentage of Infusions Associated With =1 Local AE (Including and Excluding Infections) During Infusion or Within 72 Hours of Completion of Infusion [Time Frame: During infusion or within 72 hours of completion of infusion]

IgG Maximum Plasma Concentration (C_max) for Participants Aged 12 Years and Older [Time Frame: PK 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.]

IgG Minimum Plasma Concentration (C_min) for Participants Aged 12 Years and Older [Time Frame: PK 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]

Median Rate of AEs Temporally Associated or Related to Study Drug Per Infusion [Time Frame: Throughout the study period (17 months)]

Percentage of SC Doses of IGIV, 10% and rHuPH20 Tolerated at 1 Infusion Site [Time Frame: During infusion or within 60 minutes of completion of the infusion]

Tetanus Antibody Maximum Plasma Concentration (C_max) for Participants Aged 12 Years and Older [Time Frame: PK 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.]

Number of Participants Who Developed Neutralizing Antibodies to Recombinant Human Hyaluronidase (rHuPH20) [Time Frame: Throughout the study period (17 months)]

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

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) [Time Frame: Throughout the study period (17 months)]

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

Percentage of Participants Reporting =1 Temporally Associated AEs [Time Frame: During infusion or within 72 hours of completion of infusion]

Antibody Levels to Hepatitis B [Time Frame: 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]

Percentage of Participants Reporting =1 Temporally Associated Moderate or Severe AEs [Time Frame: During infusion or within 72 hours of completion of infusion]

Rate of Days in Hospital [Time Frame: Monthly, for up to 17 months]

Percentage of Infusions Resulting in =1 Temporally Associated Moderate or Severe AEs Within 72 Hours of Completion of Infusion [Time Frame: During infusion or within 72 hours of completion of infusion]

Antibody Levels to Measles [Time Frame: 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]

Percentage of Participants With =1 Systemic AE (Including and Excluding Infections) During Infusion or Within 72 Hours of Completion of Infusion [Time Frame: During infusion or within 72 hours of completion of infusion]

Bioavailability (AUC) of IgG After SC Administration of IGIV, 10%, Given With and Without rHuPH20 [Time Frame: PK: 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.]

Percentage of Participants With =1 Local AE At Any Time During the Study [Time Frame: During infusion or within 72 hours of completion of infusion]

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

Percentage of Infusions Resulting in =1 Temporally Associated AEs [Time Frame: During infusion or within 72 hours of completion of infusion]

Tetanus Antibody Minimum Plasma Concentration (C_min) for Participants Aged 12 Years and Older [Time Frame: PK 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.]

Rate of AEs Determined to be Related to the Study Drug by the Investigator Per Participant [Time Frame: Throughout the study period (17 months)]

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

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

Trough Levels of IgG After Administration of IGIV, 10% Given Via IV or SC With rHuPH20 [Time Frame: IgG 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.]

Rate of Temporally Associated AEs Per Infusion [Time Frame: During infusion or within 72 hours of completion of infusion]

Time to Maximum H. Influenzae Antibody Concentration (T-max) for Participants Aged 12 Years and Older [Time Frame: PK 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 Antibody Clearance (CL) for Participants Aged 12 Years and Older [Time Frame: PK 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 Antibody Concentration (T-max) for Participants Aged 12 Years and Older [Time Frame: PK 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.]

Rate of Acute Physician Visits [Time Frame: Monthly, for up to 17 months]

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

Tetanus Antibody Area Under the Curve (AUC)/Week for Participants Aged 12 Years and Older [Time Frame: PK 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 Antibody Terminal Half Life (T1/2) for Participants Aged 12 Years and Older [Time Frame: PK 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.]

H. Influenzae Antibody Area Under the Curve (AUC)/Week for Participants Aged 12 Years and Older [Time Frame: PK 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.]

H. Influenzae Antibody Maximum Plasma Concentration (C_max) for Participants Aged 12 Years and Older [Time Frame: PK 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.]

IgG Terminal Half Life (T1/2) for Participants Aged 12 Years and Older [Time Frame: PK 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.]

Percentage of Infusions Associated With =1 Local AE At Any Time During the Study [Time Frame: At any time during the study]

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) [Time Frame: Throughout the study period (17 months)]

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

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

Rate of Days Off School or Work [Time Frame: Monthly, for up to 17 months]

Rate of Days on Antibiotics [Time Frame: Monthly, for up to 17 months]

Trough Levels of IgG Subclasses After Administration of IGIV, 10% Given Via IV or SC With rHuPH20 [Time Frame: IgG 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]

Secondary ID(s)

160603

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 03/12/2015
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00814320