Phase 3
N=77
Phase 2/3 Study of IGSC, 20% in PIDD
Primary Immunodeficiency Diseases (PID)
Bottom Line
View on ClinicalTrials.gov: NCT01218438 ↗Enrolled (actual)
77
Serious AEs
2.0%
Results posted
Feb 2017
Primary outcome: Primary: Rate of Acute Serious Bacterial Infections Per Year (ASBI) — 0.012 Estimated infections/ year — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Immune Globulin Intravenous (Human), 10% Solution (Biological); Immune Globulin Subcutaneous (Human), 20% Solution (Drug)
- Age
- Pediatric, Adult, Older Adult · 2+ yrs
- Sex
- All
- Sponsor
- Baxalta now part of Shire
- Primary completion
- Mar 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Rate of Acute Serious Bacterial Infections Per Year (ASBI) |
0.012 | <0.0001 sig |
| SECONDARY Annual Rate of All Infections Per Participant |
3.86; 2.41 | — |
| SECONDARY Annual Rate of Sinus Infections Per Participant |
0.97; 0.69 | — |
| SECONDARY Annual Rate of Fever Episodes Per Participant |
0.61; 0.13 | — |
| SECONDARY Annual Rate of Days Off School/Work or Days Unable to Perform Normal Daily Activities Due to Illness or Infection Per Participant |
3.20; 1.16 | — |
| SECONDARY Annual Rate of Days on Antibiotics Per Participant |
63.20; 57.59 | — |
| SECONDARY Annual Rate of Hospitalizations for Illness or Infection Per Participant |
0.05; 0.02 | — |
| SECONDARY Annual Rate of Days of Hospitalizations for Illness or Infection Per Participant |
0.20; 0.11 | — |
| SECONDARY Annual Rate of Acute (Urgent or Unscheduled) Physician Visits, or Visits to the Emergency Room for Illness or Infection Per Participant |
1.73; 0.86 | — |
| SECONDARY Bioavailability of IGSC, 20% as Measured by the Ratio of the Geometric Means of Immunoglobulin G (IgG) AUCSC (Epoch 4) to IgG AUCIV,0-τ (Standardized to 1 Week) (Epoch 1) Adjusted for Dose and Dosing Frequency (Participants ≥12 Years Old) |
1.0855 | — |
| SECONDARY Trough Levels of IgG (Total), and IgG Subclasses at the End of the Treatment Intervals |
11.58; 10.19; 14.77; 14.20; 14.74; 6.23 | — |
| SECONDARY Trough Levels of Anti-Tetanus Antibody |
2.28; 3.36; 2.66; 2.55; 2.26; 1.92 | — |
| SECONDARY Trough Levels of Anti-Haemophilus Influenza B Antibody |
2.91; 2.71; 3.08; 2.42; 2.47; 2.82 | — |
| SECONDARY Trough Levels of Anti-Hepatitis B Antibody |
266.6; 357.8; 402.6; 376.6; 392.2; 301.1 | — |
| SECONDARY Pharmacokinetics Parameters for Immunoglobulin G (IgG): Area Under the Curve (AUC) |
352.05; 410.40; 108.33; 115.21 | — |
| SECONDARY Pharmacokinetics Parameters for Immunoglobulin G (IgG): Dose Per Weight-adjusted Area Under the Curve (AUC) |
606.99; 796.30; 472.50; 536.05 | — |
| SECONDARY Pharmacokinetics Parameters for Immunoglobulin G (IgG): Clearance (CL) for Immune Globulin Administered Intravenously (IGIV) and Apparent Clearance for Immune Globulin Administered Subcutaneously (IGSC) |
1.65; 1.26; 2.12; 1.87 | — |
| SECONDARY Pharmacokinetics Parameters for Immunoglobulin G (IgG): Maximum Concentration (Cmax) |
27.09; 24.85; 17.31; 19.31 | — |
| SECONDARY Pharmacokinetics Parameters for Immunoglobulin G (IgG): Time to Maximum Concentration (Tmax) |
6.94; 5.84; 54.19; 78.68 | — |
| SECONDARY Pharmacokinetics Parameters for Immunoglobulin G (IgG): Minimum Concentration (Cmin) |
12.03; 10.37; 13.85; 14.00 | — |
| SECONDARY Pharmacokinetics Parameters for Haemophilus Influenza B Antibody: Area Under the Curve (AUC) |
80.79; 123.05; 29.51; 30.64 | — |
| SECONDARY Pharmacokinetics Parameters for Haemophilus Influenza B Antibody: Dose Per Weight-adjusted Area Under the Curve (AUC) |
139.29; 239.99; 128.72; 141.78 | — |
| SECONDARY Pharmacokinetics Parameters for Haemophilus Influenza B Antibody: Clearance (CL) for Immune Globulin Administered Intravenously (IGIV) and Apparent Clearance (CL/F) for Immune Globulin Administered Subcutaneously |
7.18; 4.17; 7.77; 7.05 | — |
| SECONDARY Pharmacokinetics Parameters for Haemophilus Influenza B Antibody: Maximum Concentration (Cmax) |
6.31; 7.22; 4.40; 4.86 | — |
| SECONDARY Pharmacokinetics Parameters for Haemophilus Influenza B Antibody: Time to Maximum Concentration (Tmax) |
3.11; 3.71; 70.67; 66.87 | — |
| SECONDARY Pharmacokinetics Parameters for Haemophilus Influenza B Antibody: Minimum Concentration (Cmin) |
2.82; 3.13; 3.97; 3.71 | — |
| SECONDARY Correction Factor to Determine the Individually Adapted Dose in Study 170904 Epoch 4 (Dose Adjustment Table) |
1.16; 1.14; 1.12; 1.11; 1.10; 1.09 | — |
| SECONDARY Number of Serious (SAEs) and Non-serious Adverse Events (AEs) (Including and Excluding Infections) Deemed Related to the Investigational Product Per Participant |
1.039; 2.122; 1.039; 2.122; 0.013; 0 | — |
| SECONDARY Number of Serious (SAEs) and Non-serious Adverse Events (AEs) (Including and Excluding Infections) Deemed Related to the Investigational Product Per Infusion |
0.247; 0.036; 0.247; 0.036; 0.003; 0 | — |
| SECONDARY Number of Serious (SAEs) and Non-serious Adverse Events (AEs) (Including and Excluding Infections) Regardless of Relationship to the Investigational Product Per Participant |
3.325; 9.014; 2.338; 6.297; 0.013; 0.027 | — |
| SECONDARY Number of Serious (SAEs) and Non-serious Adverse Events (AEs) (Including and Excluding Infections) Regardless of Relationship to the Investigational Product Per Infusion |
0.390; 0.114; 0.296; 0.079; 0.003; 0.000 | — |
| SECONDARY Number of Adverse Events (AEs) (Including and Excluding Infections) That Begin During or Within 72 Hours of Completion of Infusion Per Participant |
1.377; 4.581; 1.260; 3.703; 0.013; 0 | — |
| SECONDARY Number of Adverse Events (AEs) (Including and Excluding Infections) That Begin During or Within 72 Hours of Completion of Infusion Per Infusion |
0.327; 0.078; 0.299; 0.063; 0.003; 0 | — |
| SECONDARY Number of Adverse Events (AEs) (Including and Excluding Infections) That Begin During or Within 24 Hours of Completion of Infusion Per Participant |
0.961; 3.365; 0.948; 3.027; 0; 0 | — |
| SECONDARY Number of Adverse Events (AEs) (Including and Excluding Infections) That Begin During or Within 24 Hours of Completion of Infusion Per Infusion |
0.228; 0.058; 0.225; 0.052; 0; 0 | — |
| SECONDARY Number of Adverse Events (AEs) (Including and Excluding Infections) That Begin During or Within 1 Hour of Completion of Infusion Per Participant |
0.662; 1.865; 0.662; 1.797; 0; 0 | — |
| SECONDARY Number of Adverse Events (AEs) (Including and Excluding Infections) That Begin During or Within 1 Hour of Completion of Infusion |
0.157; 0.032; 0.157; 0.031; 0; 0 | — |
| SECONDARY Causally Related and/or Temporally Associated Adverse Events (AEs) Per Infusion |
0.336; 0.079; 0.309; 0.064; 0.003; 0 | — |
| SECONDARY Percentage of Infusions Associated With One or More Local Non-serious Adverse Events (Non-SAEs) |
0.9; 1.8 | — |
| SECONDARY Percentage of Participants Reporting One or More Local Non-serious Adverse Events (Non-SAEs) |
3.9; 31.1 | — |
| SECONDARY Number of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped Due to Tolerability Concerns or AEs |
4; 5; 5; 2; 0; 1 | — |
| SECONDARY Percentage of Participants for Whom the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped Due to Tolerability Concerns or AEs |
1.3; 5.4; 6.5; 1.4; 0.0; 1.4 | — |
| SECONDARY Percentage of Infusions Tolerated With Intravenous or Subcutaneous Administration |
100; 100 | — |
| SECONDARY Short Term Tolerance - Change in Systolic Blood Pressure: Immune Globulin Administered Intravenously (Human), 10% (IV 10%), Infusion 1 |
61; 1; 1; 0; 0; 10 | — |
| SECONDARY Short Term Tolerance - Change in Systolic Blood Pressure: Immune Globulin Administered Intravenously (Human), 10% (IV 10%), Infusion 2 |
62; 0; 0; 0; 0; 5 | — |
| SECONDARY Short Term Tolerance - Change in Systolic Blood Pressure: Immune Globulin Administered Intravenously (Human), 10% (IV 10%), Infusion 3 |
59; 0; 0; 0; 0; 9 | — |
| SECONDARY Short Term Tolerance - Change in Systolic Blood Pressure: Immune Globulin Administered Subcutaneously (Human), 20% (SC 20%), Infusion 1 |
38; 1; 0; 0; 0; 1 | — |
| SECONDARY Short Term Tolerance - Change in Systolic Blood Pressure: Immune Globulin Administered Subcutaneously (Human), 20% (SC 20%), Infusion 2 |
35; 2; 0; 0; 0; 2 | — |
| SECONDARY Short Term Tolerance - Change in Systolic Blood Pressure: Immune Globulin Administered Subcutaneously (Human), 20% (SC 20%), Infusion 3 |
32; 0; 0; 0; 0; 2 | — |
| SECONDARY Short Term Tolerance - Change in Diastolic Blood Pressure: Immune Globulin Administered Intravenously (Human), 10% (IV 10%), Infusion 1 |
69; 0; 1; 0; 0; 2 | — |
| SECONDARY Short Term Tolerance - Change in Diastolic Blood Pressure: Immune Globulin Administered Intravenously (Human), 10% (IV 10%), Infusion 2 |
67; 0; 1; 0; 0; 3 | — |
| SECONDARY Short Term Tolerance - Change in Diastolic Blood Pressure: Immune Globulin Administered Intravenously (Human), 10% (IV 10%), Infusion 3 |
69; 1; 0; 0; 0; 1 | — |
| SECONDARY Short Term Tolerance - Change in Diastolic Blood Pressure: Immune Globulin Administered Subcutaneously (Human), 20% (SC 20%), Infusion 1 |
41; 1; 0; 0; 0; 0 | — |
| SECONDARY Short Term Tolerance - Change in Diastolic Blood Pressure: Immune Globulin Administered Subcutaneously (Human), 20% (SC 20%), Infusion 2 |
37; 0; 0; 0; 0; 2 | — |
| SECONDARY Short Term Tolerance - Change in Diastolic Blood Pressure: Immune Globulin Administered Subcutaneously (Human), 20% (SC 20%), Infusion 3 |
35; 0; 0; 0; 0; 0 | — |
| SECONDARY Short Term Tolerance - Change in Heart Rate (Pulse): Immune Globulin Administered Intravenously (Human), 10% (IV 10%), Infusion 1 |
61; 3; 0; 0; 0; 8 | — |
| SECONDARY Short Term Tolerance - Change in Heart Rate (Pulse): Immune Globulin Administered Intravenously (Human), 10% (IV 10%), Infusion 2 |
53; 3; 1; 0; 0; 9 | — |
| SECONDARY Short Term Tolerance - Change in Heart Rate (Pulse): Immune Globulin Administered Intravenously (Human), 10% (IV 10%), Infusion 3 |
55; 1; 0; 0; 0; 9 | — |
| SECONDARY Short Term Tolerance - Change in Heart Rate (Pulse): Immune Globulin Administered Subcutaneously (Human), 20% (SC 20%), Infusion 1 |
40; 0; 0; 0; 0; 1 | — |
| SECONDARY Short Term Tolerance - Change in Heart Rate (Pulse): Immune Globulin Administered Subcutaneously (Human), 20% (SC 20%), Infusion 2 |
36; 0; 0; 0; 0; 2 | — |
| SECONDARY Short Term Tolerance - Change in Heart Rate (Pulse): Immune Globulin Administered Subcutaneously (Human), 20% (SC 20%), Infusion 3 |
32; 2; 0; 0; 0; 1 | — |
| SECONDARY Short Term Tolerance - Change in Respiratory Rate: Immune Globulin Administered Intravenously (Human), 10% (IV 10%), Infusion 1 |
32; 5; 0; 0; 0; 7 | — |
| SECONDARY Short Term Tolerance - Change in Respiratory Rate: Immune Globulin Administered Intravenously (Human), 10% (IV 10%), Infusion 2 |
35; 2; 0; 0; 0; 11 | — |
| SECONDARY Short Term Tolerance - Change in Respiratory Rate: Immune Globulin Administered Intravenously (Human), 10% (IV 10%), Infusion 3 |
32; 4; 0; 0; 0; 6 | — |
| SECONDARY Short Term Tolerance - Change in Respiratory Rate: Immune Globulin Administered Subcutaneously (Human), 20% (SC 20%), Infusion 1 |
18; 1; 0; 0; 0; 9 | — |
| SECONDARY Short Term Tolerance - Change in Respiratory Rate: Immune Globulin Administered Subcutaneously (Human), 20% (SC 20%), Infusion 2 |
18; 1; 0; 0; 0; 4 | — |
| SECONDARY Short Term Tolerance - Change in Respiratory Rate: Immune Globulin Administered Subcutaneously (Human), 20% (SC 20%), Infusion 3 |
13; 6; 0; 0; 0; 5 | — |
| SECONDARY Short Term Tolerance - Change in Body Temperature: Immune Globulin Administered Intravenously (Human), 10% (IV 10%), Infusion 1 |
77; 0; 0; 0; 0; 0 | — |
| SECONDARY Short Term Tolerance - Change in Body Temperature: Immune Globulin Administered Intravenously (Human), 10% (IV 10%), Infusion 2 |
73; 0; 0; 0; 0; 1 | — |
| SECONDARY Short Term Tolerance - Change in Body Temperature: Immune Globulin Administered Intravenously (Human), 10% (IV 10%), Infusion 3 |
72; 0; 0; 0; 0; 2 | — |
| SECONDARY Short Term Tolerance - Change in Body Temperature: Immune Globulin Administered Subcutaneously (Human), 20% (SC 20%), Infusion 1 |
45; 0; 0; 0; 0; 0 | — |
| SECONDARY Short Term Tolerance - Change in Body Temperature: Immune Globulin Administered Subcutaneously (Human), 20% (SC 20%), Infusion 2 |
41; 0; 0; 0; 0; 0 | — |
| SECONDARY Short Term Tolerance - Change in Body Temperature: Immune Globulin Administered Subcutaneously (Human), 20% (SC 20%), Infusion 3 |
36; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Laboratory Confirmed Hemolysis That Occurred Following Investigational Product Administration |
0; 0 | — |
| SECONDARY Quality of Life- Pediatric Quality of Life Inventory^TM (PEDS-QL^TM) (Observer: Parent) for the Age Group 2 to 7 Years |
95.31; 93.75; 96.88; 92.19; 1.56; 1.56 | — |
| SECONDARY Quality of Life- PEDS-QL^TM (Observer: Participant) for the Age Group 8 to 13 Years of Age |
89.06; 90.63; 87.50; 93.75; 0.00; 6.25 | — |
| SECONDARY Quality of Life- Short-Form 36v2 (SF-36v2) for the Age Group 14 Years and Older |
48.61; 52.82; 50.72; 50.72; 0.00; 0.00 | — |
| SECONDARY Treatment Satisfaction Questionnaire for Medication (TSQM) - 2 to 12 Years Old |
83.33; 88.89; 83.33; 91.67; 0.00; 0.00 | — |
| SECONDARY Treatment Satisfaction Questionnaire for Medication (TSQM) - 13 Years and Older |
77.78; 80.56; 83.33; 83.33; 0.00; 0.00 | — |
| SECONDARY Life Quality Index - 2 to 12 Years Old |
32.0; 31.0; 35.0; 34.5; 0.0; -0.5 | — |
| SECONDARY Life Quality Index - 13 Years and Older |
34.0; 34.5; 37.0; 38.5; 1.0; 3.0 | — |
Summary
The purpose of this study is to develop a 20% subcutaneous (SC) immunoglobulin preparation for the treatment of patients with primary immunodeficiency diseases (PIDD).
Eligibility Criteria
Main Inclusion Criteria:
- Documented diagnosis of a form of primary humoral immunodeficiency involving defective antibody formation and requiring gammaglobulin replacement as defined according to the IUIS Scientific Committee, 2011 and by diagnostic criteria according to Conley et al. (1999). The diagnosis must be confirmed by the Medical Director prior to first treatment with the investigational product (IP) in the study.
- Participant is 2 years or older at the time of screening, and has a minimum body weight of 13 kg.
- Written informed consent has been obtained from either the participant or the participant's legally authorized representative prior to any study-related procedures and study product administration
- Participant has been receiving a stable monthly equivalent dose of IgG at an average minimum dose equivalent to 300 mg/kg bodyweight (BW)/4 weeks and a maximum dose equivalent to 1.0 gram/kg BW/4 weeks, for a minimum of 12 weeks prior to first treatment with the IP in the study.
- Serum trough level of IgG > 500 mg/dL at screening
- Participant is willing and able to comply with the requirements of the protocol
Main Exclusion Criteria:
- Participant has known history of or is positive at 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
- Abnormal laboratory values at screening meeting any one of the following criteria (abnormal tests may be repeated once to determine if they are persistent):
- Persistent alanine aminotransferase (ALT) and aspartate amino transferase(AST) > 2.5 times the upper limit of normal for the testing laboratory
- Persistent severe neutropenia (defined as an absolute neutrophil count [ANC] ≤500/mm^3)
- Creatinine clearance (CLcr) value that is 9 g/dL or myeloma or macroglobulinemia (IgM) or paraproteinemia
- Severe dermatitis that would preclude adequate sites for safe product administration
- Women of childbearing potential meeting any one of the following criteria:
- Participant presents with a positive pregnancy test
- Participant is breast feeding
- Participant intends to begin nursing during the course of the study
- Participant does not agree to employ adequate birth-control measures (e.g. intrauterine device, diaphragm or condom [for male partner] with spermicidal jelly or foam, or birth control pills/patches) throughout the course of the study
- Participation in another clinical study and exposure to an investigational product or device within 30 days prior to study enrollment (exception: treatment in a previous Baxter immunoglobulin study)
- Participant is scheduled to participate in another (non-Baxter) non-observational (interventional) clinical study involving an investigational product or device during the course of the study
Data sourced from ClinicalTrials.gov (NCT01218438). 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.