Tolerability and Safety of Immune Globulin Subcutaneous Solution (IGSC) and rHuPH20 in PID

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Baxalta US Inc.
ClinicalTrials.gov Identifier:
NCT01175213
First received: August 3, 2010
Last updated: May 24, 2016
Last verified: May 2016

August 3, 2010
May 24, 2016
July 2010
August 2013   (final data collection date for primary outcome measure)
  • Annual Rate of Serious Bacterial Infections [ Time Frame: Throughout the efficacy period only (from 60 to 729 days) ] [ Designated as safety issue: No ]

    The point estimate of the annual rate of validated acute serious bacterial infections (VASBIs) per participant per year was provided during subcutaneous (SC) administration of Immune Globulin Subcutaneous Solution (IGSC), 10%, after SC administration of human recombinant hyaluronidase (rHuPH20).

    This efficacy outcome measure was only applicable prior to the safety follow-up i.e. before discontinuation of rHuPH20.

  • Annual Rate of All Infections [ Time Frame: Throughout the efficacy period only (from 60 to 729 days) ] [ Designated as safety issue: No ]

    Annualized rate of infections per participant as defined by MedDRA system organ class (SOC) "infections and infestations".

    The point estimate of the annual rate of all infections was provided during subcutaneous (SC) administration of Immune Globulin Subcutaneous Solution (IGSC), 10%, after SC administration of human recombinant hyaluronidase (rHuPH20).

    This efficacy outcome measure was only applicable prior to the safety follow-up i.e. before discontinuation of rHuPH20.

  • Trough Levels of IgG Maintained During the Study Period in Relation to Dose Frequency [ Time Frame: Throughout the efficacy period only (from 60 to 729 days) ] [ Designated as safety issue: No ]

    Immunoglobulin (IgG) steady state trough levels were measured in relation to dose frequency by measuring in relation to treatment interval (2-, 3- or 4-week intervals).

    Initially participants were administered subcutaneous (SC) infusions of Immune Globulin Subcutaneous Solution (IGSC), 10%, after SC administration of human recombinant hyaluronidase (rHuPH20) [or IV infusions of IGSC, 10% only] at the treatment intervals and dose determined by epoch 2 of study 160603 (3- or 4-week intervals).

    After 3 treatment intervals (either 3- or 4- week intervals), participants changed to a 2-week treatment interval, if agreed with participant and investigator, with the dose adjusted to 1/2 of the 4-week dose or 2/3 of the 3-week dose, whichever was applicable. The rHuPH20 dose was adjusted relative to the new IGSC, 10% dose in order to achieve a dose ratio of 75 U/g IgG.

    This efficacy outcome measure was only applicable prior to the safety follow-up i.e. before discontinuation of rHuPH20.

To evaluate the long-term tolerability and safety of IGSC given SC after an SC administration of recombinant human hyaluronidase (rHuPH20) in subjects with PID [ Time Frame: 21 months ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01175213 on ClinicalTrials.gov Archive Site
  • The Annual Rate of Serious Adverse Events (SAEs), Related and Not Related to Study Drugs [ Time Frame: Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer. ] [ Designated as safety issue: Yes ]

    Separated into age groups as described below and into related (related to either study drug) and not related (not related to either or both study drugs).

    Study drugs are Immune Globulin Subcutaneous Solution (IGSC), 10% and recombinant human hyaluronidase (rHuPH20).

  • Percentage of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Interrupted or Stopped for Tolerability Concerns or for AEs [ Time Frame: Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer. ] [ Designated as safety issue: Yes ]
  • Percentage of Infusions Associated With One or More Moderate or Severe AEs (Including and Excluding Infections) That Begin During or Within 72 Hours of Completion of an Infusion [ Time Frame: Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer. ] [ Designated as safety issue: Yes ]
  • Number of Participants Who Develop Antibodies and Neutralizing Antibodies to rHuPH20 [ Time Frame: Throughout entire study period for 160603 (1 year 11 months) and 160902 (2 years 11 months) ] [ Designated as safety issue: Yes ]

    Participants who develop binding antibodies and/or neutralizing antibodies to recombinant human hyaluronidase (rHuPH20) from study 160603 and/ or from this study (160902) are included here.

    This study (160902) is an extension of study 160603. Study 160603 was divided into 2 study epochs. In epoch 1 of study 160603 participants were treated with intravenous (IV) administration of Immune Globulin Subcutaneous Solution (IGSC), 10%. In epoch 2 of study 160603 participants were treated with subcutaneous (SC) administration of IGSC, 10% after SC administration of rHuPH20. Only participants who completed study 160603 were eligible to be screened and enrolled in this study (160902).

    In this study, participants started on same doses of IGSC, 10% and rHuPH20 that were used for the last infusions in epoch 2 of study 160603.

  • Percentage of Participants Who Develop Antibodies and Neutralizing Antibodies to rHuPH20 [ Time Frame: Throughout entire study period for 160603 (1 year 11 months) and 160902 (2 years 11 months) ] [ Designated as safety issue: Yes ]

    Participants who develop binding antibodies and/or neutralizing antibodies to recombinant human hyaluronidase (rHuPH20) from study 160603 and/ or from this study (160902) are included here.

    This study (160902) is an extension of study 160603. Study 160603 was divided into 2 study epochs. In epoch 1 of study 160603 participants were treated with intravenous (IV) administration of Immune Globulin Subcutaneous Solution (IGSC), 10%. In epoch 2 of study 160603 participants were treated with subcutaneous (SC) administration of IGSC, 10% after SC administration of rHuPH20. Only participants who completed study 160603 were eligible to be screened and enrolled in this study (160902).

    In this study, participants started on same doses of IGSC, 10% and rHuPH20 that were used for the last infusions in epoch 2 of study 160603.

  • Number of Participants With AEs Related to Anti-rHuPH20 Titers [ Time Frame: Throughout entire study period for 160603 (1 year 11 months) and 160902 (2 years 11 months) ] [ Designated as safety issue: Yes ]
  • Percentage of Participants With AEs Related to Anti-rHuPH20 Titers [ Time Frame: Throughout entire study period for 160603 (1 year 11 months) and 160902 (2 years 11 months) ] [ Designated as safety issue: Yes ]
  • Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to the Study Drug, and Severity (A-F). [ Time Frame: Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer. ] [ Designated as safety issue: Yes ]

    Categories presented as Preferred Term-Seriousness-Relatedness-Severity. The following codes are to be used:

    Seriousness: non-SAE-non-serious AE; SAE-serious AE Relatedness to study drug: R (related to either study drug); NR (not related to either or both study drugs). Study drugs are Immune Globulin Subcutaneous Solution, 10% (IGSC, 10%) and recombinant human hyaluronidase (rHuPH20) Severity: Mild; Mod (Moderate); Severe

    Preferred terms abbreviated:

    ADHD - Attention Deficit/Hyperactivity Disorder COPD - Chronic Obstructive Pulmonary Disease

    Other abbreviations:

    CPK - Creatinine Phosphokinase Inc. - Increased Dis - Disease Sml- small

  • Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to the Study Drug, and Severity (G-M). [ Time Frame: Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer. ] [ Designated as safety issue: Yes ]

    Categories presented as Preferred Term-Seriousness-Relatedness-Severity. The following codes are to be used:

    Seriousness: non-SAE-non-serious AE; SAE-serious AE Relatedness to study drug: R (related to either study drug); NR (not related to either or both study drugs). Study drugs are Immune Globulin Subcutaneous Solution, 10% (IGSC, 10%) and recombinant human hyaluronidase (rHuPH20) Severity: Mild; Mod (Moderate); Severe

  • Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to the Study Drug, and Severity (N-Z). [ Time Frame: Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer. ] [ Designated as safety issue: Yes ]

    Categories presented as Preferred Term-Seriousness, Relatedness, Severity. The following codes are to be used:

    Seriousness: non-SAE-non-serious AE; SAE-serious AE Relatedness to study drug: R (related to either study drug); NR (not related to either or both study drugs). Study drugs are Immune Globulin Subcutaneous Solution, 10% (IGSC, 10%) and recombinant human hyaluronidase (rHuPH20) Severity: Mild; Mod (Moderate); Severe

    Preferred terms abbreviated:

    Infection - Inf.

  • Rate of All AEs Per Participant Categorized by MedDRA Preferred Terms, Seriousness and Severity (A-F). [ Time Frame: Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer. ] [ Designated as safety issue: Yes ]

    Categories presented as Preferred Term-Seriousness-Severity. The following codes are to be used:

    Seriousness: non-SAE-non-serious AE; SAE-serious AE Severity: Mild; Mod (Moderate); Sev (Severe)

    Preferred terms abbreviated:

    ADHD - Attention Deficit/Hyperactivity Disorder COPD - Chronic Obstructive Pulmonary Disease

    Other abbreviations:

    Inc. - Increased Dis. - Disease

  • Rate of All AEs Per Participant Categorized by MedDRA Preferred Terms, Seriousness and Severity (G-M). [ Time Frame: Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer. ] [ Designated as safety issue: Yes ]

    Categories presented as Preferred term-Seriousness-Severity. The following codes are to be used:

    Seriousness: non-SAE-non-serious AE; SAE-serious AE Severity: Mild; Mod (Moderate); Sev (Severe)

  • Rate of All AEs Per Participant Categorized by MedDRA Preferred Terms, Seriousness and Severity (N-Z). [ Time Frame: Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer. ] [ Designated as safety issue: Yes ]

    Categories presented as Preferred term-Seriousness-Severity. The following codes are to be used:

    Seriousness: non-SAE-non-serious AE; SAE-serious AE Severity: Mild; Mod (Moderate); Sev (Severe)

  • Rate of All AEs Per Infusion Categorized by MedDRA Preferred Terms, Seriousness and Severity (A-F). [ Time Frame: Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer. ] [ Designated as safety issue: Yes ]

    Categories presented as Preferred term-Seriousness-Severity. The following codes are to be used:

    Seriousness: non-SAE-non-serious adverse event; SAE- serious adverse event Severity: Mild; Mod (Moderate); Sev (Severe)

    Preferred terms abbreviated:

    ADHD - Attention Deficit/Hyperactivity Disorder COPD - Chronic Obstructive Pulmonary Disease

    Other abbreviations:

    Inc. - Increased Dis. - Disease

  • Rate of All AEs Per Infusion Categorized by MedDRA Preferred Terms, Seriousness and Severity (G-M). [ Time Frame: Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer. ] [ Designated as safety issue: Yes ]

    Categories presented as Preferred term-Seriousness-Severity. The following codes are to be used:

    Seriousness: non-SAE-non-serious AE; SAE-serious AE Severity: Mild; Mod (Moderate); Sev (Severe)

  • Rate of All AEs Per Infusion Categorized by MedDRA Preferred Terms, Seriousness and Severity (N-Z). [ Time Frame: Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer. ] [ Designated as safety issue: Yes ]

    Categories presented as Preferred term-Seriousness-Severity. The following codes are to be used:

    Seriousness: non-SAE-non-serious AE; SAE-serious AE Severity: Mild; Mod (Moderate); Sev (Severe)

  • Rate of AEs Per Participant (Including and Excluding Infections) Determined by the Investigator to be Related to the Study Drug That Occur at Any Time During the Study ("Related") [ Time Frame: Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer. ] [ Designated as safety issue: Yes ]

    Categories presented as adverse event (AE) type : Total, Local, Systemic including infections, Systemic excluding infections, and Severity (Mild, Moderate, Severe, Total).

    All of these adverse events are non-serious AEs.

  • Rate of AEs Per Infusion (Including and Excluding Infections) Determined by the Investigator to be Related to the Study Drug That Occur at Any Time During the Study ("Related") [ Time Frame: Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer. ] [ Designated as safety issue: Yes ]

    Categories presented as adverse event (AE) type : Total, Local, Systemic including infections, Systemic excluding infections, and Severity (Mild, Moderate, Severe, Total).

    All of these adverse events are non-serious AEs.

  • Rate of AEs Per Participant (Including and Excluding Infections) Temporarily Associated With the Infusion [ Time Frame: Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer. ] [ Designated as safety issue: Yes ]

    Categories presented as adverse event (AE) type : Total, Local, Systemic including infections, Systemic excluding infections, Seriousness: Serious AE (SAE), non-serious AE (nsAE) and Severity (Mild, Moderate, Severe, Total).

    All of these adverse events are non-serious AEs.

  • Rate of AEs Per Infusion (Including and Excluding Infections) Temporarily Associated With the Infusion [ Time Frame: Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer. ] [ Designated as safety issue: Yes ]

    Categories presented as adverse event (AE) type : Total, Local, Systemic including infections, Systemic excluding infections, Seriousness: Serious AE (SAE), non-serious AE (non-SAE) and Severity (Mild, Moderate, Severe, Total).

    All of these adverse events are non-serious AEs.

  • Percentage of Infusions Associated With One or More Local AEs (Including and Excluding Infections), at Any Time During the Study [ Time Frame: Throughout entire study period (up to 3 years). Duration of participation for each participant is variable depending on date of enrollment and their anti-rHuPH20 binding antibody titer. ] [ Designated as safety issue: Yes ]
To monitor the long-term efficacy of IGSC given subcutaneously after an administration of rHuPH20 in subjects with PID [ Time Frame: 21 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Tolerability and Safety of Immune Globulin Subcutaneous Solution (IGSC) and rHuPH20 in PID
Long-Term Tolerability and Safety of Immune Globulin Subcutaneous (IGSC) Solution Administered Subcutaneously Following Administration of Recombinant Human Hyaluronidase (rHuPH20) in Subjects With Primary Immunodeficiency Diseases

The original purpose of the study was to assess the long-term safety, tolerability, and practicability of the subcutaneous (SC) treatment with Immune Globulin Subcutaneous Solution (IGSC), 10% facilitated with recombinant human hyaluronidase (rHuPH20) in participants with Primary Immunodeficiency Diseases (PID) who had completed Baxalta (formerly Baxter) Clinical Study Protocol No. 160603.

Following a discussion with the FDA at the end of July 2012, all participants still active in the study stopped treatment with rHuPH20 to assure safety of the participants participating in the study and went into a safety follow-up.

During this safety follow-up period, participants underwent either SC treatment with IGSC, 10% or intravenous (IV) treatment with Immune Globulin Intravenous (Human) (IGIV), 10%. The IV or SC administration route was at the discretion of the participant and the investigator.

IGSC, 10% is the same product as IGIV, 10%. IGSC, 10% is generally quoted when administration is subcutaneous (SC) and IGIV, 10% is generally quoted when administration is intravenous (IV).

IGSC, 10% is abbreviated to IGI, 10% (IMMUNE GLOBULIN INFUSION (HUMAN), 10%)

In the US the product is licensed (trade name GAMMAGARD LIQUID) for the IV and SC replacement therapy of antibody deficiency in patients with PID.

In the EU this product is licensed (trade name KIOVIG)

IGSC, 10% with rHuPH20 established name is Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase.

US trade name is HYQVIA EU trade name is HyQvia

Interventional
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Primary Immunodeficiency Diseases (PID)
  • Biological: IGSC - rHuPH20 then IGSC or IGIV

    Treatment Period:

    As this was an extension of Study 160603 (NCT00814320), participants continued on the same doses and treatment intervals of Immune Globulin Subcutaneous Solution (IGSC), 10% and recombinant human hyaluronidase (rHuPH20) used for the last infusions in epoch 2 of Study 160603.

    After 3 infusions, participants changed to 2-week infusions, if agreed with investigator and participant.

    Followed by

    Safety Follow-up Period:

    Participants were treated either subcutaneously (SC) with IGSC, 10% weekly (dose-weekly equivalent of most recent intravenous [IV] dose adjusted per body weight x 1.37) or IV with Immune Globulin Intravenous (Human) (IGIV), 10%, every 3-4 weeks (weekly dose equivalent was 100% of the most recent IV dose) as agreed with the investigator and participant.

    Other Names:
    • HYQVIA (IGSC, 10% with rHuPH20 [US])
    • HyQvia (IGSC, 10% with rHuPH20 [EU])
    • GAMMAGARD LIQUID (IGSC, 10% [US])
    • KIOVIG (IGSC, 10% [EU])
    • IMMUNE GLOBULIN INTRAVENOUS (HUMAN), 10% (IGIV, 10%)
    • IMMUNE GLOBULIN INFUSION (HUMAN), 10% (IGI, 10%)
  • Biological: IGIV, 10% only

    Participants were treated with IGIV, 10% only throughout the study.

    Note: IGIV, 10% is the same product as IGSC, 10%

    Other Names:
    • GAMMAGARD LIQUID (US)
    • KIOVIG (EU)
    • IMMUNE GLOBULIN INTRAVENOUS (HUMAN), 10% (IGIV, 10%)
    • IMMUNE GLOBULIN INFUSION (HUMAN), 10% (IGI, 10%)
    • IMMUNE GLOBULIN SUBCUTANEOUS (HUMAN), 10% (IGSC, 10%)
  • Experimental: IGSC - rHuPH20 then IGSC or IGIV

    Efficacy and safety of subcutaneous (SC) administration of Immune Globulin Subcutaneous Solution (IGSC), 10% after SC administration of recombinant human hyaluronidase (rHuPH20). Participants then went into a safety follow-up with either SC administration of IGSC, 10% or intravenous (IV) administration of Immune Globulin Intravenous (Human) (IGIV), 10%, only. The IV or SC administration route was at the discretion of the participant and the investigator.

    Note: IGIV, 10% is the same product as IGSC, 10%.

    Intervention: Biological: IGSC - rHuPH20 then IGSC or IGIV
  • Experimental: IGIV, 10% only

    Participants were treated with Immune Globulin Intravenous (Human) (IGIV), 10% only, via the intravenous (IV) route throughout the study.

    Note: IGIV, 10% is the same product as IGSC, 10%.

    Intervention: Biological: IGIV, 10% only
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
66
August 2013
August 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Participant has completed or is about to complete Baxalta (formerly Baxter) Clinical Study Protocol No. 160603. Participants who have discontinued rHuPH20 and reverted to intravenous or subcutaneous treatment due to an anti-rHuPH20 antibody also may enroll for long-term safety monitoring.
  • Participant/caretaker has reviewed, signed and dated informed consent
  • Participant is willing and able to comply with the requirements of the protocol

Exclusion Criteria:

  • Participant has a serious medical condition such that the participant's safety or medical care would be impacted by participation in Study 160902
  • Participant is scheduled to participate in another non-Baxalta (formerly Baxter) clinical study involving an investigational product or investigational device during the course of this study
  • If female of childbearing potential, participant is pregnant or has a negative pregnancy test and does not agree to employ adequate birth control measures for the duration of the study
Both
2 Years and older   (Child, Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01175213
160902
No
Not Provided
Not Provided
Baxalta US Inc.
Baxalta US Inc.
Not Provided
Study Director: Leman Yel, MD Baxalta US Inc.
Baxalta US Inc.
May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP