Phase 2/3 Study of IGSC, 20% in PIDD

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01218438
• Date of registration: 08/10/2010
• Prospective Registration: Yes
• Primary sponsor: Baxalta now part of Shire
• Public title: Phase 2/3 Study of IGSC, 20% in PIDD
• Scientific title: A Clinical Study of Immune Globulin Subcutaneous (Human), 20% Solution (IGSC, 20%) for the Evaluation of Efficacy, Safety, Tolerability and Pharmacokinetics in Subjects With Primary Immunodeficiency Diseases (PIDD)
• Date of first enrolment: January 2013
• Target sample size: 86
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01218438
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2/Phase 3

Countries of recruitment

Canada, United States

Contacts

• Name: Leman Yel, MD
• Affiliation: Baxter Healthcare Corporation

Key inclusion & exclusion 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 < 60% of normal for age and gender either
measured, or calculated according to the Cockcroft-Gault formula

- Malignancy (other than adequately treated basal cell or squamous cell carcinoma of the
skin or carcinoma in situ of the cervix), unless the disease-free period prior to
screening exceeds 5 years

- Participant is receiving anti-coagulation therapy (low dose aspirin at =325 mg/day is
permitted) or has a history of thrombotic episodes (including deep vein thrombosis,
myocardial infarction, cerebrovascular accident, pulmonary embolism) or sickle cell
disease with crisis within 12 months prior to screening or a history of thrombophilia

- Abnormal protein loss (protein losing enteropathy, nephrotic syndrome)

- Anemia that would preclude phlebotomy for laboratory studies according to standard
practice at the site

- Acute serious bacterial infection within 3 months prior to screening

- Ongoing history of hypersensitivity or persistent reactions (urticaria, breathing
difficulty, severe hypotension, or anaphylaxis) following intravenous immunoglobulin,
subcutaneous immunoglobulin, and/or Immune Serum Globulin (ISG) infusions

- Severe immunoglobulin A (IgA) deficiency (less than 0.07g/L) with known anti-IgA
antibodies and a history of hypersensitivity

- Participant is on continuous systemic antibacterial antibiotics at doses sufficient to
treat or prevent bacterial infections, and, in the opinion of the investigator, cannot
stop these for the duration of the study without putting the patient at risk of
increased infections

- Participant has active infection and is receiving antibiotic therapy for the treatment
of infection at the time of screening

- Bleeding disorder or thrombocytopenia with a platelet count less than 20,000/µL, or
who, in the opinion of the investigator, would be at significant risk of increased
bleeding or bruising as a result of subcutaneous therapy

- Total protein > 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



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

Health Condition(s) or Problem(s) studied

Primary Immunodeficiency Diseases (PID)

Intervention(s)

Biological: Immune Globulin Intravenous (Human), 10% Solution

Drug: Immune Globulin Subcutaneous (Human), 20% Solution

Primary Outcome(s)

Rate of Acute Serious Bacterial Infections Per Year (ASBI) [Time Frame: 1 year]

Secondary Outcome(s)

Annual Rate of Days on Antibiotics Per Participant [Time Frame: 1 year]

Annual Rate of Sinus Infections Per Participant [Time Frame: 1 year]

Number of Adverse Events (AEs) (Including and Excluding Infections) That Begin During or Within 24 Hours of Completion of Infusion Per Infusion [Time Frame: Within 24 hours of completion of infusion]

Number of Adverse Events (AEs) (Including and Excluding Infections) That Begin During or Within 72 Hours of Completion of Infusion Per Infusion [Time Frame: Within 72 hours of completion of infusion]

Percentage of Participants Reporting One or More Local Non-serious Adverse Events (Non-SAEs) [Time Frame: Up to 20 months (throughout entire study)]

Pharmacokinetics Parameters for Haemophilus Influenza B Antibody: Area Under the Curve (AUC) [Time Frame: Epoch 1: 3 week IV interval: Weeks 10-13. Epoch 1: 4 week IV interval: Weeks 9-13. Epoch 2: Subcutaneous (SC) weeks 9-10. Epoch 4: SC weeks 17-18]

Pharmacokinetics Parameters for Immunoglobulin G (IgG): Clearance (CL) for Immune Globulin Administered Intravenously (IGIV) and Apparent Clearance for Immune Globulin Administered Subcutaneously (IGSC) [Time Frame: Epoch 1: 3 week IV interval: Weeks 10-13. Epoch 1: 4 week IV interval: Weeks 9-13. Epoch 2: Subcutaneous (SC) weeks 9-10. Epoch 4: SC weeks 17-18]

Pharmacokinetics Parameters for Immunoglobulin G (IgG): Dose Per Weight-adjusted Area Under the Curve (AUC) [Time Frame: Epoch 1: 3 week IV interval: Weeks 10-13. Epoch 1: 4 week IV interval: Weeks 9-13. Epoch 2: Subcutaneous (SC) weeks 9-10. Epoch 4: SC weeks 17-18]

Quality of Life- Pediatric Quality of Life Inventory^TM (PEDS-QL^TM) (Observer: Parent) for the Age Group 2 to 7 Years [Time Frame: Up to 20 months (throughout entire study)]

Quality of Life- PEDS-QL^TM (Observer: Participant) for the Age Group 8 to 13 Years of Age [Time Frame: Up to 20 months (throughout entire study)]

Short Term Tolerance - Change in Heart Rate (Pulse) [Time Frame: Within 30 minutes pre-infusion, during infusion and within 30 minutes post infusion at first 3 infusions in Epoch 1 & 2]

Annual Rate of Days Off School/Work or Days Unable to Perform Normal Daily Activities Due to Illness or Infection Per Participant [Time Frame: 1 year]

Life Quality Index - 2 to 12 Years Old [Time Frame: Up to 20 months (throughout entire study)]

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 [Time Frame: Epoch 1: 3 week IV interval: Weeks 10-13. Epoch 1: 4 week IV interval: Weeks 9-13. Epoch 2: Subcutaneous (SC) weeks 9-10. Epoch 4: SC weeks 17-18]

Annual Rate of All Infections Per Participant [Time Frame: 1 year]

Correction Factor to Determine the Individually Adapted Dose in Study 170904 Epoch 4 (Dose Adjustment Table) [Time Frame: 29 weeks]

Pharmacokinetics Parameters for Haemophilus Influenza B Antibody: Maximum Concentration (Cmax) [Time Frame: Epoch 1: 3 week IV interval: Weeks 10-13. Epoch 1: 4 week IV interval: Weeks 9-13. Epoch 2: Subcutaneous (SC) weeks 9-10. Epoch 4: SC weeks 17-18]

Number of Adverse Events (AEs) (Including and Excluding Infections) That Begin During or Within 72 Hours of Completion of Infusion Per Participant [Time Frame: Within 72 hours of completion of infusion]

Annual Rate of Hospitalizations for Illness or Infection Per Participant [Time Frame: 1 year]

Number of Serious (SAEs) and Non-serious Adverse Events (AEs) (Including and Excluding Infections) Regardless of Relationship to the Investigational Product Per Participant [Time Frame: Up to 20 months per subject (throughout entire study)]

Percentage of Infusions Associated With One or More Local Non-serious Adverse Events (Non-SAEs) [Time Frame: Up to 20 months (throughout entire study)]

Number of Serious (SAEs) and Non-serious Adverse Events (AEs) (Including and Excluding Infections) Regardless of Relationship to the Investigational Product Per Infusion [Time Frame: Up to 20 months per subject (throughout entire study)]

Pharmacokinetics Parameters for Haemophilus Influenza B Antibody: Minimum Concentration (Cmin) [Time Frame: Epoch 1: 3 week IV interval: Weeks 10-13. Epoch 1: 4 week IV interval: Weeks 9-13. Epoch 2: Subcutaneous (SC) weeks 9-10. Epoch 4: SC weeks 17-18]

Treatment Satisfaction Questionnaire for Medication (TSQM) - 2 to 12 Years Old [Time Frame: Up to 20 months per subject (throughout entire study)]

Trough Levels of Anti-Hepatitis B Antibody [Time Frame: Epoch 1: 3 week IV interval- weeks 1, 4, 7, 10, 13. Epoch 1: 4 week IV interval- weeks 1, 5, 9, 13. Epochs 2 & 3: Subcutaneous (SC) weeks 5, 9. Epoch 4: SC weeks 1, 9, 17, 29, 40 (week dependent on time to establish "Adjusted Dose" in Epoch 2)]

Trough Levels of Anti-Haemophilus Influenza B Antibody [Time Frame: Epoch 1: 3 week IV interval- weeks 1, 4, 7, 10, 13. Epoch 1: 4 week IV interval- weeks 1, 5, 9, 13. Epochs 2 & 3: Subcutaneous (SC) weeks 5, 9. Epoch 4: SC weeks 1, 9, 17, 29, 40 (week dependent on time to establish "Adjusted Dose" in Epoch 2)]

Life Quality Index - 13 Years and Older [Time Frame: Up to 20 months per subject (throughout entire study)]

Number of Adverse Events (AEs) (Including and Excluding Infections) That Begin During or Within 1 Hour of Completion of Infusion [Time Frame: Within 1 hour of completion of infusion]

Number of Participants With Laboratory Confirmed Hemolysis That Occurred Following Investigational Product Administration [Time Frame: Epoch 1: 3 week IV interval- weeks 0, 10. Epoch 1: 4 week IV interval- weeks 0, 9. Epoch 3: Subcutaneous (SC) week 9. Epoch 4: SC weeks 17, 18, 40]

Annual Rate of Fever Episodes Per Participant [Time Frame: 1 year]

Bioavailability of IGSC, 20% as Measured by the Ratio of the Geometric Means of Immunoglobulin G (IgG) AUCSC (Epoch 4) to IgG AUCIV,0-t (Standardized to 1 Week) (Epoch 1) Adjusted for Dose and Dosing Frequency (Participants =12 Years Old) [Time Frame: Epoch 1: 3 week IV administration interval: Week 10, 11, 12, 13. Epoch 1: 4 week IV interval: Week 9, 10, 11, 12, 13. Epoch 4 Subcutaneous administration weeks 17, 18]

Number of Serious (SAEs) and Non-serious Adverse Events (AEs) (Including and Excluding Infections) Deemed Related to the Investigational Product Per Infusion [Time Frame: Up to 20 months per subject (throughout entire study)]

Causally Related and/or Temporally Associated Adverse Events (AEs) Per Infusion [Time Frame: Within 72 hours post infusion for Temporally Associated AEs; End of each Study Epoch (Epoch 1, Epoch 2, Epoch 3, and Epoch 4) for Causally Related AEs]

Short Term Tolerance - Change in Blood Pressure [Time Frame: Within 30 minutes pre-infusion, during infusion and within 30 minutes post infusion at first 3 infusions in Epoch 1 & 2]

Pharmacokinetics Parameters for Haemophilus Influenza B Antibody: Time to Maximum Concentration (Tmax) [Time Frame: Epoch 1: 3 week IV interval: Weeks 10-13. Epoch 1: 4 week IV interval: Weeks 9-13. Epoch 2: Subcutaneous (SC) weeks 9-10. Epoch 4: SC weeks 17-18]

Pharmacokinetics Parameters for Immunoglobulin G (IgG): Area Under the Curve (AUC) [Time Frame: Epoch 1: 3 week IV interval: Weeks 10-13. Epoch 1: 4 week IV interval: Weeks 9-13. Epoch 2: Subcutaneous (SC) weeks 9-10. Epoch 4: SC weeks 17-18]

Pharmacokinetics Parameters for Immunoglobulin G (IgG): Maximum Concentration (Cmax) [Time Frame: Epoch 1: 3 week IV interval: Weeks 10-13. Epoch 1: 4 week IV interval: Weeks 9-13. Epoch 2: Subcutaneous (SC) weeks 9-10. Epoch 4: SC weeks 17-18]

Short Term Tolerance - Change in Respiratory Rate [Time Frame: Within 30 minutes pre-infusion, during infusion and within 30 minutes post infusion at first 3 infusions in Epoch 1 & 2]

Treatment Satisfaction Questionnaire for Medication (TSQM) - 13 Years and Older [Time Frame: Up to 20 months per subject (throughout entire study)]

Annual Rate of Acute (Urgent or Unscheduled) Physician Visits, or Visits to the Emergency Room for Illness or Infection Per Participant [Time Frame: 1 year]

Number of Adverse Events (AEs) (Including and Excluding Infections) That Begin During or Within 1 Hour of Completion of Infusion Per Participant [Time Frame: Within 1 hour of completion of infusion]

Number of Adverse Events (AEs) (Including and Excluding Infections) That Begin During or Within 24 Hours of Completion of Infusion Per Participant [Time Frame: Within 24 hours of completion of infusion]

Number of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped Due to Tolerability Concerns or AEs [Time Frame: Up to 20 months (throughout entire study)]

Percentage of Infusions Tolerated With Intravenous or Subcutaneous Administration [Time Frame: Up to 20 months (throughout entire study)]

Percentage of Participants for Whom the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped Due to Tolerability Concerns or AEs [Time Frame: Up to 20 months (throughout entire study)]

Pharmacokinetics Parameters for Immunoglobulin G (IgG): Time to Maximum Concentration (Tmax) [Time Frame: Epoch 1: 3 week IV interval: Weeks 10-13. Epoch 1: 4 week IV interval: Weeks 9-13. Epoch 2: Subcutaneous (SC) weeks 9-10. Epoch 4: SC weeks 17-18]

Quality of Life- Short-Form 36v2 (SF-36v2) for the Age Group 14 Years and Older [Time Frame: Up to 20 months (throughout entire study)]

Trough Levels of Anti-Tetanus Antibody [Time Frame: Epoch 1: 3 week IV interval- weeks 1, 4, 7, 10, 13. Epoch 1: 4 week IV interval- weeks 1, 5, 9, 13. Epochs 2 & 3: Subcutaneous (SC) weeks 5, 9. Epoch 4: SC weeks 1, 9, 17, 29, 40 (week dependent on time to establish "Adjusted Dose" in Epoch 2)]

Annual Rate of Days of Hospitalizations for Illness or Infection Per Participant [Time Frame: 1 year]

Number of Serious (SAEs) and Non-serious Adverse Events (AEs) (Including and Excluding Infections) Deemed Related to the Investigational Product Per Participant [Time Frame: Up to 20 months per subject (throughout entire study)]

Pharmacokinetics Parameters for Haemophilus Influenza B Antibody: Dose Per Weight-adjusted Area Under the Curve (AUC) [Time Frame: Epoch 1: 3 week IV interval: Weeks 10-13. Epoch 1: 4 week IV interval: Weeks 9-13. Epoch 2: Subcutaneous (SC) weeks 9-10. Epoch 4: SC weeks 17-18]

Pharmacokinetics Parameters for Immunoglobulin G (IgG): Minimum Concentration (Cmin) [Time Frame: Epoch 1: 3 week IV interval: Weeks 10-13. Epoch 1: 4 week IV interval: Weeks 9-13. Epoch 2: Subcutaneous (SC) weeks 9-10. Epoch 4: SC weeks 17-18]

Short Term Tolerance - Change in Body Temperature [Time Frame: Within 30 minutes pre-infusion, during infusion and within 30 minutes post infusion at first 3 infusions in Epoch 1 & 2]

Trough Levels of IgG (Total), and IgG Subclasses at the End of the Treatment Intervals [Time Frame: Epoch 1: 3 week IV interval- weeks 0, 1, 4, 7, 10, 13. Epoch 1: 4 week IV interval- weeks 0, 1, 5, 9, 13. Epochs 2 & 3: Subcutaneous (SC) weeks 5, 9. Epoch 4: SC weeks 1, 9, 17, 29, 40 (week dependent on time to establish "Adjusted Dose" in Epoch 2)]

Secondary ID(s)

170904

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 15/02/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01218438