Clinical trial NCT01175213: Tolerability and Safety of Immune Globulin Subcutaneous Solution (IGSC) and rHuPH20 in PID
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Immunodeficiency Diseases (PID)
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-08-04
Enrollment: 66
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The original purpose of the study is 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 have completed Baxter Clinical Study Protocol No. 160603.

Following a discussion with the FDA, 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 intravenous (IV) or SC treatment with IGSC, 10%. The IV or SC administration route was at the discretion of the participant and the investigator.

Detailed description: IGSC, 10% is the same product as IMMUNE GLOBULIN INTRAVENOUS (HUMAN), 10% (IGIV, 10%) quoted in study 160603.

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 intravenous (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 Innume Glubulin Infusion 10% (Human) with Recombinant Human Hyualuronidase.

US trade name is HYQVIA EU trade name is HyQvia

Eligibility criteria: Inclusion Criteria:

* Participant has completed or is about to complete 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-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

Primary outcomes:
measure: Annual Rate of Serious Bacterial Infections
timeFrame: Throughout the efficacy period only (from 60 to 729 days)
measure: Annual Rate of All Infections
timeFrame: Throughout the efficacy period only (from 60 to 729 days)
measure: Trough Levels of IgG Maintained During the Study Period in Relation to Dose Frequency
timeFrame: Throughout the efficacy period only (from 60 to 729 days)
Secondary outcomes:
measure: The Annual Rate of Serious Adverse Events (SAEs), Related and Not Related to Study Drugs
timeFrame: 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.
measure: Percentage of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Interrupted or Stopped for Tolerability Concerns or for AEs
timeFrame: 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.
measure: 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
timeFrame: 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.
measure: Number of Participants Who Develop Antibodies and Neutralizing Antibodies to rHuPH20
timeFrame: Throughout entire study period for 160603 (1 year 11 months) and 160902 (2 years 11 months)
measure: Percentage of Participants Who Develop Antibodies and Neutralizing Antibodies to rHuPH20
timeFrame: Throughout entire study period for 160603 (1 year 11 months) and 160902 (2 years 11 months)
measure: Number of Participants With AEs Related to Anti-rHuPH20 Titers
timeFrame: Throughout entire study period for 160603 (1 year 11 months) and 160902 (2 years 11 months)
measure: Percentage of Participants With AEs Related to Anti-rHuPH20 Titers
timeFrame: Throughout entire study period for 160603 (1 year 11 months) and 160902 (2 years 11 months)
measure: Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to the Study Drug, and Severity (A-F).
timeFrame: 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.
measure: Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to the Study Drug, and Severity (G-M).
timeFrame: 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.
measure: Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to the Study Drug, and Severity (N-Z).
timeFrame: 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.
measure: Rate of All AEs Per Participant Categorized by MedDRA Preferred Terms, Seriousness and Severity (A-F).
timeFrame: 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.
measure: Rate of All AEs Per Participant Categorized by MedDRA Preferred Terms, Seriousness and Severity (G-M).
timeFrame: 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.
measure: Rate of All AEs Per Participant Categorized by MedDRA Preferred Terms, Seriousness and Severity (N-Z).
timeFrame: 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.
measure: Rate of All AEs Per Infusion Categorized by MedDRA Preferred Terms, Seriousness and Severity (A-F).
timeFrame: 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.
measure: Rate of All AEs Per Infusion Categorized by MedDRA Preferred Terms, Seriousness and Severity (G-M).
timeFrame: 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.
measure: Rate of All AEs Per Infusion Categorized by MedDRA Preferred Terms, Seriousness and Severity (N-Z).
timeFrame: 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.
measure: 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")
timeFrame: 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.
measure: 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")
timeFrame: 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.
measure: Rate of AEs Per Participant (Including and Excluding Infections) Temporarily Associated With the Infusion
timeFrame: 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.
measure: Rate of AEs Per Infusion (Including and Excluding Infections) Temporarily Associated With the Infusion
timeFrame: 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.
measure: Percentage of Infusions Associated With One or More Local AEs (Including and Excluding Infections), at Any Time During the Study
timeFrame: 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.
Other outcomes:
Locations:
city: Cypress
country: United States
state: California
city: Irvine
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Centennial
country: United States
state: Colorado
city: North Palm Beach
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Hinsdale
country: United States
state: Illinois
city: Bronx
country: United States
state: New York
city: Dallas
country: United States
state: Texas
city: Galveston
country: United States
state: Texas
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Wasserman RL, Melamed I, Stein MR, Engl W, Sharkhawy M, Leibl H, Puck J, Rubinstein A, Kobrynski L, Gupta S, Grant AJ, Ratnayake A, Richmond WG, Church J, Yel L, Gelmont D. Long-Term Tolerability, Safety, and Efficacy of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Human Immunoglobulin for Primary Immunodeficiency. J Clin Immunol. 2016 Aug;36(6):571-82. doi: 10.1007/s10875-016-0298-x. Epub 2016 May 25.
citation: Wasserman RL, Gupta S, Stein M, Rabbat CJ, Engl W, Leibl H, Yel L. Infection rates and tolerability of three different immunoglobulin administration modalities in patients with primary immunodeficiency diseases. Immunotherapy. 2022 Mar;14(4):215-224. doi: 10.2217/imt-2021-0256. Epub 2021 Dec 21.