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

NCT01175213 | Completed Phase 3 Results

• 1 other identifier: 160902
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 11

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.

Conditions

Primary Immunodeficiency Diseases (PID)

Outcome Measures

Primary Outcomes (3)

• Annual Rate of Serious Bacterial Infections

  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.

  Throughout the efficacy period only (from 60 to 729 days)

• Annual Rate of All Infections

  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.

  Throughout the efficacy period only (from 60 to 729 days)

• Trough Levels of IgG Maintained During the Study Period in Relation to Dose Frequency

  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.

  Throughout the efficacy period only (from 60 to 729 days)

Secondary Outcomes (21)

• The Annual Rate of Serious Adverse Events (SAEs), Related and Not Related to Study Drugs

  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.

• Percentage of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Interrupted or Stopped for Tolerability Concerns or for AEs

  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.

• 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

  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.

• Number of Participants Who Develop Antibodies and Neutralizing Antibodies to rHuPH20

  Throughout entire study period for 160603 (1 year 11 months) and 160902 (2 years 11 months)

• Percentage of Participants Who Develop Antibodies and Neutralizing Antibodies to rHuPH20

  Throughout entire study period for 160603 (1 year 11 months) and 160902 (2 years 11 months)

Study Arms (3)

SC/IGSC, 10% with rHuPH20 followed by SC of IGSC, 10% (safety)

EXPERIMENTAL

Efficacy and safety of subcutaneous (SC) administration of Immune Globulin Subcutaneous Solution (IGSC), 10% after SC administration of recombinant human hyaluronidase (rHuPH20) followed by Safety of SC of IGSC, 10% only (safety follow-up)

Biological: SC treatment with IGSC, 10% with rHuPH20 followed by SC/IGSC, 10% only (safety)

SC/IGSC, 10% with rHuPH20 followed by IV of IGSC, 10% (safety

EXPERIMENTAL

Efficacy and safety of subcutaneous (SC) administration of Immune Globulin Subcutaneous Solution (IGSC), 10% after SC administration of recombinant human hyaluronidase (rHuPH20) followed by Safety of intravenous (IV) administration of IGSC, 10% only (safety follow-up)

Biological: SC treatment with IGSC, 10% with rHuPH20 followed by IV/IGSC, 10% only (safety)

IV treatment with IGSC, 10% only

EXPERIMENTAL

Partial efficacy (trough levels of immunoglobulin G \[IgG\] only) and safety of intravenous (IV) administration of IGSC, 10% only. This was for participants enrolled in the study who had anti-rHuPH20 andibody titer from study160603

Biological: IV treatment with IGSC, 10%

Interventions

SC treatment with IGSC, 10% with rHuPH20 followed by SC/IGSC, 10% only (safety) BIOLOGICAL

Participants are to continue on the same doses and treatment intervals of IGSC, 10% adjusted for body weight, and rHuPH20 that were used for the last infusions in Study epoch 2 of Study 160603 (NCT00814320). After 3 infusions, participants are to change treatment to a 2-week interval, if agreed with participant and investigator. During this safety follow-up period, participants are treated with IGSC, 10% via the SC route. Treatment occurred once every week. The dose was the weekly equivalent of the most recent IV dose (adjusted per body weight) and multiplied by 1.37.

Also known as: HYQVIA (IGSC, 10% with rHuPH20 [US]), 10% with rHuPH20 [EU]), GAMMAGARD LIQUID (IGSC, 10% [US]), KIOVIG (IGSC, 10% [EU])

SC/IGSC, 10% with rHuPH20 followed by SC of IGSC, 10% (safety)

SC treatment with IGSC, 10% with rHuPH20 followed by IV/IGSC, 10% only (safety) BIOLOGICAL

Participants are to continue on the same doses and treatment intervals of IGSC, 10% adjusted for body weight, and rHuPH20 that were used for the last infusions in Study epoch 2 of Study 160603 (NCT00814320). After 3 infusions, participants are to change treatment to a 2-week interval, if agreed with participant and investigator. During this safety follow-up period, participants are treated with IGSC, 10% via the intravenous (IV) route. Treatment occurred once every 3-4 weeks. The weekly dose equivalent was 100% of the most recent IV dose.

Also known as: GAMMAGARD LIQUID (IGSC, 10% [US]), KIOVIG (IGSC, 10% [EU]), HyQvia (IGSC, 10% with rHuPH20 [EU]), 10% with rHuPH20 [US])

SC/IGSC, 10% with rHuPH20 followed by IV of IGSC, 10% (safety

IV treatment with IGSC, 10% BIOLOGICAL

During this safety follow-up period, participants are treated with IGSC, 10% via the intravenous (IV) route.

Also known as: GAMMAGARD LIQUID (US), KIOVIG (EU)

IV treatment with IGSC, 10% only

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Baxalta now part of Shire: lead

Study Sites (11)

Unknown Facility

Cypress, California, United States

Location

Unknown Facility

Irvine, California, United States

Location

Unknown Facility

Los Angeles, California, United States

Location

Unknown Facility

San Francisco, California, United States

Location

Unknown Facility

Centennial, Colorado, United States

Location

Unknown Facility

North Palm Beach, Florida, United States

Location

Unknown Facility

Atlanta, Georgia, United States

Location

Unknown Facility

Hinsdale, Illinois, United States

Location

Unknown Facility

The Bronx, New York, United States

Location

Unknown Facility

Dallas, Texas, United States

Location

Unknown Facility

Galveston, Texas, United States

Location

Related Publications (2)

• 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.

  PMID: 27220317 RESULT

• 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.

  PMID: 34931880 DERIVED

MeSH Terms

Conditions

Primary Immunodeficiency Diseases

Interventions

Single Person; Safety; Therapeutics

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Marital Status; Family Characteristics; Demography; Population Characteristics; Socioeconomic Factors; Accident Prevention; Accidents; Public Health; Environment and Public Health

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2010
• First Posted: August 4, 2010
• Study Start: July 28, 2010
• Primary Completion: August 6, 2013
• Study Completion: August 6, 2013
• Last Updated: May 19, 2021
• Results First Posted: May 26, 2016

Record last verified: 2021-04

Locations

US (11)