Primary Immunodeficiency Diseases (PID)Phase 3NCT01175213
Tolerability and Safety of Immune Globulin Subcutaneous Solution (IGSC) and rHuPH20 in PID
A Phase 3 study testing SC treatment with IGSC, 10% with rHuPH20 followed by SC/IGSC, 10% only (safety), SC treatment with IGSC, 10% with rHuPH20 followed by IV/IGSC, 10% only (safety) and IV treatment with IGSC, 10% in people with Primary Immunodeficiency Diseases (PID), run by Baxalta now part of Shire at 11 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Primary Immunodeficiency Diseases (PID)
- What is being tested?
- SC treatment with IGSC, 10% with rHuPH20 followed by SC/IGSC, 10% only (safety), SC treatment with IGSC, 10% with rHuPH20 followed by IV/IGSC, 10% only (safety) and IV treatment with IGSC, 10%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 11 sitesUnited States
- Study dates
- 28 Jul 2010to 6 Aug 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Study site
Atlanta, Georgia
Study site
Centennial, Colorado
Study site
Cypress, California
Study site
Dallas, Texas
Study site
Galveston, Texas
Study site
Hinsdale, Illinois
Study site
Irvine, California
Study site
Los Angeles, California
Study site
North Palm Beach, Florida
Study site
San Francisco, California
Study site
The Bronx, New York
About this study
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
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.
Read the 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
- Conditions
- Primary Immunodeficiency Diseases (PID)
- Being tested
- SC treatment with IGSC, 10% with rHuPH20 followed by SC/IGSC, 10% only (safety), SC treatment with IGSC, 10% with rHuPH20 followed by IV/IGSC, 10% only (safety), IV treatment with IGSC, 10%
- Medical subject headings
- Primary Immunodeficiency Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SC treatment with IGSC, 10% with rHuPH20 followed by SC/IGSC, 10% only (safety)Biological
Also called HYQVIA (IGSC, 10% with rHuPH20 [US]), 10% with rHuPH20 [EU]), GAMMAGARD LIQUID (IGSC
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.
SC treatment with IGSC, 10% with rHuPH20 followed by IV/IGSC, 10% only (safety)Biological
Also called GAMMAGARD LIQUID (IGSC, 10% [US]), KIOVIG (IGSC, 10% [EU])
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.
IV treatment with IGSC, 10%Biological
Also called GAMMAGARD LIQUID (US), KIOVIG (EU)
During this safety follow-up period, participants are treated with IGSC, 10% via the intravenous (IV) route.
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: 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 Receives: Biological: IV treatment with IGSC, 10% |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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
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).
Measured: 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
Measured: 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
Measured: 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
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.
Measured: 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
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.
Measured: Throughout entire study period for 160603 (1 year 11 months) and 160902 (2 years 11 months)
Number of Participants With AEs Related to Anti-rHuPH20 Titers
Measured: Throughout entire study period for 160603 (1 year 11 months) and 160902 (2 years 11 months)
Percentage of Participants With AEs Related to Anti-rHuPH20 Titers
Measured: Throughout entire study period for 160603 (1 year 11 months) and 160902 (2 years 11 months)
Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to the Study Drug, and Severity (A-F).
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
Measured: 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 All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to the Study Drug, and Severity (G-M).
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
Measured: 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 All AEs Categorized by MedDRA Preferred Terms, Seriousness, Relatedness to the Study Drug, and Severity (N-Z).
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.
Measured: 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.
Rate of All AEs Per Participant Categorized by MedDRA Preferred Terms, Seriousness and Severity (A-F).
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
Measured: 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.
Rate of All AEs Per Participant Categorized by MedDRA Preferred Terms, Seriousness and Severity (G-M).
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)
Measured: 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.
Rate of All AEs Per Participant Categorized by MedDRA Preferred Terms, Seriousness and Severity (N-Z).
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)
Measured: 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.
Rate of All AEs Per Infusion Categorized by MedDRA Preferred Terms, Seriousness and Severity (A-F).
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
Measured: 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.
Rate of All AEs Per Infusion Categorized by MedDRA Preferred Terms, Seriousness and Severity (G-M).
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)
Measured: 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.
Rate of All AEs Per Infusion Categorized by MedDRA Preferred Terms, Seriousness and Severity (N-Z).
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)
Measured: 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.
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")
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.
Measured: 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.
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")
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.
Measured: 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.
Rate of AEs Per Participant (Including and Excluding Infections) Temporarily Associated With the Infusion
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.
Measured: 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.
Rate of AEs Per Infusion (Including and Excluding Infections) Temporarily Associated With the Infusion
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.
Measured: 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 Local AEs (Including and Excluding Infections), at Any Time During the Study
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2010 (estimated)
- Study start28 Jul 2010
- Primary completion6 Aug 2013
- Study completion6 Aug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Primary Immunodeficiency Diseases (PID)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baxalta now part of Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01175213
- Sponsor's protocol ID
- 160902
- Status last verified
- Apr 2021
- First submitted
- 3 Aug 2010
- Last updated
- 19 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 27220317Wasserman 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.
PubMed 34931880
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01175213
- Acronym / sponsor ID
- 160902
- Conditions
- Primary Immunodeficiency Diseases (PID)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Baxalta now part of ShireIndustry (pharma, biotech, devices)
- Study start
- 28 Jul 2010 (actual)
- Primary completion
- 6 Aug 2013 (actual)
- Study completion
- 6 Aug 2013 (actual)
- First posted
- 4 Aug 2010 (estimated)
- Results
- Posted 26 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| SC/IGSC, 10% with rHuPH20 followed by SC of IGSC, 10% (safety) | Experimental | Biological: SC treatment with IGSC, 10% with rHuPH20 followed by SC/IGSC, 10% only (safety)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) |
| SC/IGSC, 10% with rHuPH20 followed by IV of IGSC, 10% (safety | Experimental | Biological: SC treatment with IGSC, 10% with rHuPH20 followed by IV/IGSC, 10% only (safety)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) |
| IV treatment with IGSC, 10% only | Experimental | Biological: IV treatment with IGSC, 10%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 |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SC treatment with IGSC, 10% with rHuPH20 followed by SC/IGSC, 10% only (safety)Also: HYQVIA (IGSC, 10% with rHuPH20 [US]), 10% with rHuPH20 [EU]), GAMMAGARD LIQUID (IGSCParticipants 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. | Biological | 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)Also: GAMMAGARD LIQUID (IGSC, 10% [US]), KIOVIG (IGSC, 10% [EU])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. | Biological | SC/IGSC, 10% with rHuPH20 followed by IV of IGSC, 10% (safety |
| IV treatment with IGSC, 10%Also: GAMMAGARD LIQUID (US), KIOVIG (EU)During this safety follow-up period, participants are treated with IGSC, 10% via the intravenous (IV) route. | Biological | IV treatment with IGSC, 10% only |
Primary outcome
Annual Rate of Serious Bacterial Infections
Time frame: Throughout the efficacy period only (from 60 to 729 days)
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)
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)
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.
21 secondary outcomes
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.
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.
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.
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)
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)
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)
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)
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27220317Wasserman 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.
- Derived from this study: PubMed 34931880Wasserman 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing SC treatment with IGSC, 10% with rHuPH20 followed by SC/IGSC, 10% only (safety), SC treatment with IGSC, 10% with rHuPH20 followed by IV/IGSC, 10% only (safety) and IV treatment with IGSC, 10% in people with Primary Immunodeficiency Diseases (PID), run by Baxalta now part of Shire at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Annual Rate of Serious Bacterial Infections (time frame: Throughout the efficacy period only (from 60 to 729 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01175213, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2021.