Phase 3
N=87
Gammagard Liquid and rHuPH20 in PID
Primary Immunodeficiency Diseases (PID)
Bottom Line
View on ClinicalTrials.gov: NCT00814320 ↗Enrolled (actual)
87
Serious AEs
8.8%
Results posted
Dec 2015
Primary outcome: Primary: Validated Acute Serious Bacterial Infection (VASBI) Rate — 0.025 Estimated infections/year — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Recombinant human hyaluronidase (rHuPH20)+ immune globulin intravenous (IGIV) (Biological)
- Age
- Pediatric, Adult, Older Adult · 2+ yrs
- Sex
- All
- Sponsor
- Baxalta now part of Shire
- Primary completion
- Nov 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Validated Acute Serious Bacterial Infection (VASBI) Rate |
0.025 | <0.0001 sig |
| SECONDARY Bioavailability (AUC) of IgG After Administration of IGIV, 10% Given Via IV or SC With rHuPH20 in Participants ≥12 Years |
93.3 | — |
| SECONDARY Bioavailability (Trough Levels) of IgG After Administration of IGIV, 10% Given Via IV or SC With rHuPH20 in Participants Aged 2 to < 12 Years |
103.8 | — |
| SECONDARY Bioavailability (AUC) of IgG After SC Administration of IGIV, 10%, Given With and Without rHuPH20 |
118.7; 133.6; 120.4 | — |
| SECONDARY Annual Rate of All Infections Per Participant |
4.51; 2.97 | — |
| SECONDARY Trough Levels of IgG After Administration of IGIV, 10% Given Via IV or SC With rHuPH20 |
9.63; 10.40; 9.95; 10.70 | — |
| SECONDARY Trough Levels of IgG Subclasses After Administration of IGIV, 10% Given Via IV or SC With rHuPH20 |
490.0; 574.0; 455.0; 548.0; 327.0; 360.0 | — |
| SECONDARY Antibody Levels to Tetanus (Clostridium Tetani Toxoid) |
2.230; 2.320; 2.580; 2.525 | — |
| SECONDARY Antibody Levels to Haemophilus Influenzae |
2.11; 2.36; 1.97; 2.58 | — |
| SECONDARY Antibody Levels to Measles |
NA; 64.0; 768.0; 1024.0 | — |
| SECONDARY Antibody Levels to Hepatitis B |
212.9; 222.8; 242.2; 249.2 | — |
| SECONDARY IgG Minimum Plasma Concentration (C_min) for Participants Aged 12 Years and Older |
10.1; 10.4 | — |
| SECONDARY IgG Area Under the Curve (AUC)/Week for Participants Aged 12 Years and Older |
93.9; 90.5 | — |
| SECONDARY IgG Clearance (CL) for Participants Aged 12 Years and Older |
1.4; 1.6 | — |
| SECONDARY IgG Maximum Plasma Concentration (C_max) for Participants Aged 12 Years and Older |
21.9; 15.5 | — |
| SECONDARY IgG Terminal Half Life (T1/2) for Participants Aged 12 Years and Older |
35.7; 45.3 | — |
| SECONDARY Time to Maximum IgG Concentration (T-max) for Participants Aged 12 Years and Older |
0.1; 5.0 | — |
| SECONDARY Tetanus Antibody Minimum Plasma Concentration (C_min) for Participants Aged 12 Years and Older |
2.3; 2.1 | — |
| SECONDARY Tetanus Antibody Area Under the Curve (AUC)/Week for Participants Aged 12 Years and Older |
28.0; 22.6 | — |
| SECONDARY Tetanus Antibody Clearance (CL) for Participants Aged 12 Years and Older |
4.5; 5.8 | — |
| SECONDARY Tetanus Antibody Terminal Half Life (T1/2) for Participants Aged 12 Years and Older |
22.7; 30.4 | — |
| SECONDARY Tetanus Antibody Maximum Plasma Concentration (C_max) for Participants Aged 12 Years and Older |
7.3; 5.0 | — |
| SECONDARY Time to Maximum Tetanus Antibody Concentration (T-max) for Participants Aged 12 Years and Older |
0.1; 5.1 | — |
| SECONDARY H. Influenzae Antibody Minimum Plasma Concentration (C_min) for Participants Aged 12 Years and Older |
2.1; 2.2 | — |
| SECONDARY H. Influenzae Antibody Area Under the Curve (AUC)/Week for Participants Aged 12 Years and Older |
22.4; 22.5 | — |
| SECONDARY H. Influenzae Antibody Clearance (CL) for Participants Aged 12 Years and Older |
5.8; 6.4 | — |
| SECONDARY H. Influenzae Antibody Maximum Plasma Concentration (C_max) for Participants Aged 12 Years and Older |
5.5; 4.1 | — |
| SECONDARY H. Influenzae Antibody Terminal Half Life (T1/2) for Participants Aged 12 Years and Older |
33.8; 35.0 | — |
| SECONDARY Time to Maximum H. Influenzae Antibody Concentration (T-max) for Participants Aged 12 Years and Older |
0.1; 4.8 | — |
| SECONDARY Rate of Days Off School or Work |
0.23; 0.28 | — |
| SECONDARY Rate of Days on Antibiotics |
3.15; 1.69 | — |
| SECONDARY Rate of Acute Physician Visits |
0.33; 0.40 | — |
| SECONDARY Rate of Days in Hospital |
0.06; 0.02 | — |
| SECONDARY 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) |
6.9; 9.9; 4.6; 4.9; 0.0; 1.2 | — |
| SECONDARY 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) |
2.7; 1.7; 1.4; 0.4; 0.0; 0.2 | — |
| SECONDARY Rate of Temporally Associated AEs Per Infusion |
0.25; 0.21; 0.25; 0.17 | — |
| SECONDARY Percentage of Participants Reporting ≥1 Temporally Associated AEs |
66.7; 86.4; 63.2; 82.7 | — |
| SECONDARY Percentage of Infusions Resulting in ≥1 Temporally Associated AEs |
30.1; 24.5; 28.8; 22.8 | — |
| SECONDARY Percentage of Participants Reporting ≥1 Temporally Associated Moderate or Severe AEs |
36.8; 54.3; 34.5; 46.9 | — |
| SECONDARY Percentage of Infusions Resulting in ≥1 Temporally Associated Moderate or Severe AEs Within 72 Hours of Completion of Infusion |
0.0; 5.9; 0.0; 0.0 | — |
| SECONDARY Percentage of SC Doses of IGIV, 10% and rHuPH20 Tolerated at 1 Infusion Site |
100.0; 100.0 | — |
| SECONDARY Percentage of Infusions Associated With ≥1 Systemic AE During Infusion or Within 72 Hours of Completion of Infusion |
25.0; 8.3; 25.0; 8.3 | — |
| SECONDARY Percentage of Participants With ≥1 Systemic AE (Including and Excluding Infections) During Infusion or Within 72 Hours of Completion of Infusion |
64.4; 75.3; 60.9; 67.9 | — |
| SECONDARY Percentage of Infusions Associated With ≥1 Local AE (Including and Excluding Infections) During Infusion or Within 72 Hours of Completion of Infusion |
0.0; 5.9; 0.0; 5.9 | — |
| SECONDARY Percentage of Infusions Associated With ≥1 Local AE At Any Time During the Study |
0.0; 5.9; 0.0; 5.9 | — |
| SECONDARY Percentage of Participants With ≥1 Local AE During Infusion or Within 72 Hours of Completion of Infusion |
4.6; 51.9; 4.6; 51.9 | — |
| SECONDARY Percentage of Participants With ≥1 Local AE At Any Time During the Study |
5.7; 53.1; 5.7; 53.1 | — |
| SECONDARY Rate of AEs Determined to be Related to the Study Drug by the Investigator Per Participant |
0.00; 0.09; 0.00; 0.09 | — |
| SECONDARY Rate of AEs Determined to be Related to the Study Drug by the Investigator Per Infusion |
0.25; 0.22; 0.25; 0.18 | — |
| SECONDARY Frequency of Dose Corrections (If IgG Trough Levels <4.5 g/L) for Each Study Epoch (IV and SC/rHuPH20 Treatment) |
0.0; 0.0 | — |
| SECONDARY Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity (A-F) |
0; 1; 0; 1; 0; 1 | — |
| SECONDARY Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity (G-M) |
0; 1; 0; 3; 2; 2 | — |
| SECONDARY Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity (N-Z) |
4; 3; 0; 2; 0; 3 | — |
| SECONDARY Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity Per Infusion (A-F) |
0; 0.001; 0; 0.001; 0; 0.001 | — |
| SECONDARY Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity Per Infusion (G-M) |
0; 0.001; 0; 0.003; 0.005; 0.002 | — |
| SECONDARY Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity Per Infusion (N-Z) |
0.011; 0.003; 0; 0.002; 0; 0.003 | — |
| SECONDARY Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity Per Participant (A-F) |
0; 0.012; 0; 0.012; 0; 0.012 | — |
| SECONDARY Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity Per Participant (G-M) |
0; 0.012; 0; 0.037; 0.023; 0.025 | — |
| SECONDARY Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to Study Drug, and Severity Per Participant (N-Z) |
0.046; 0.037; 0; 0.025; 0; 0.037 | — |
| SECONDARY Percentage of Infusions Associated With ≥1 AE Related to Either or Both Study Drugs |
0.0; 8.3; 0.0; 8.3 | — |
| SECONDARY Percentage of Infusions Tolerated With IV and SC Administration at Dose Used in Study Epoch 2 (SC/rHuPH20 Treatment) |
100.0; 100.0 | — |
| SECONDARY Median Rate of AEs Temporally Associated or Related to Study Drug Per Infusion |
0.25; 0.22; 0.25; 0.18 | — |
| SECONDARY Number of Participants Who Developed Neutralizing Antibodies to Recombinant Human Hyaluronidase (rHuPH20) |
— | — |
| SECONDARY Percentage of Participants Who Developed Neutralizing Antibodies to Recombinant Human Hyaluronidase (rHuPH20) |
0.0 | — |
| SECONDARY Number of Participants Who Experienced a Hemoglobin Drop of >2.0 g/dL, With Evidence of Hemolysis on Further Analysis |
— | — |
| SECONDARY Percentage of Participants Who Experienced a Hemoglobin Drop of >2.0 g/dL, With Evidence of Hemolysis on Further Analysis |
— | — |
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.
Eligibility 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] 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
Data sourced from ClinicalTrials.gov (NCT00814320). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.