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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.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
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| 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) |
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| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cypress | California | United States | ||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27220317 | Result | 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. | |
| 34931880 |
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66 participants who enrolled from study 160603 were screened and all were enrolled on the study. Of these, 3 participants were treated with intravenous administration of Immune Globulin Intravenous (Human) (IGIV), 10% only i.e. did not receive rHuPH20 during this study.
Recruitment was conducted 11 clinical sites in the United States.
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| ID | Title | Description |
|---|---|---|
| FG000 | IGSC - rHuPH20 Then IGSC, 10% or IGIV, 10% Only | 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%. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| IGSC, 10%/rHuPH20 |
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| 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. |
|
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| IV treatment with IGSC, 10% | Biological | During this safety follow-up period, participants are treated with IGSC, 10% via the intravenous (IV) route. |
|
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| 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 | 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. | 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. | 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 | 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 | 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 | 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 | 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. | 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 | 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) | 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) | 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 | 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) | 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) | 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. | 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. | 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. | 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. | 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 | 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. |
| Irvine |
| California |
| United States |
| Los Angeles | California | United States |
| San Francisco | California | United States |
| Centennial | Colorado | United States |
| North Palm Beach | Florida | United States |
| Atlanta | Georgia | United States |
| Hinsdale | Illinois | United States |
| The Bronx | New York | United States |
| Dallas | Texas | United States |
| Galveston | Texas | United States |
| Derived |
| 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. |
| FG001 | 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%. |
| COMPLETED |
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| NOT COMPLETED |
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| Safety Follow-up |
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Safety Analysis Set
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| ID | Title | Description |
|---|---|---|
| BG000 | Participants Aged 2 to <12 Years | |
| BG001 | Participants Aged 12 to <16 Years | |
| BG002 | Participants Aged 16 to <65 Years | |
| BG003 | Participants Aged 65 Years and Older | |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | 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. | Safety Analysis Set excluding the 3 participants who were treated with intravenous (IV) administration of IGSC, 10% without rHuPH20 | Posted | Number | Estimated infections/year | Throughout the efficacy period only (from 60 to 729 days) |
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| Primary | 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. | Safety Analysis Set excluding the 3 participants who were treated with intravenous (IV) administration of IGSC, 10% without rHuPH20 | Posted | Number | 95% Confidence Interval | Number of infections/year | Throughout the efficacy period only (from 60 to 729 days) |
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| Primary | 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. | Safety Analysis Set | Posted | Median | 95% Confidence Interval | g/L | Throughout the efficacy period only (from 60 to 729 days) |
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| Secondary | 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). | Safety Analysis Set | Posted | Number | SAEs/year | 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. |
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| Secondary | Percentage of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Interrupted or Stopped for Tolerability Concerns or for AEs | Safety Analysis Set | Posted | Number | Percentage of infusions | 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. | Infusions | Infusions |
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| Secondary | 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 | Safety Analysis Set | Posted | Number | Percentage of infusions | 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. | Infusions | Infusions |
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| Secondary | 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. | Participants from study 160603 and this study (160902) who have received at least one infusion of rHuPH20 | Posted | Number | Number of participants | Throughout entire study period for 160603 (1 year 11 months) and 160902 (2 years 11 months) |
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| Secondary | 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. | Participants from study 160603 and this study (160902) who have received at least one infusion of rHuPH20 | Posted | Number | Percentage of participants | Throughout entire study period for 160603 (1 year 11 months) and 160902 (2 years 11 months) |
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| Secondary | Number of Participants With AEs Related to Anti-rHuPH20 Titers | All participants who had been exposed to recombinant human hyaluronidase (rHuPH20) in studies 160603 or 160902. | Posted | Number | Number of participants | Throughout entire study period for 160603 (1 year 11 months) and 160902 (2 years 11 months) |
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| Secondary | Percentage of Participants With AEs Related to Anti-rHuPH20 Titers | All participants who had been exposed to recombinant human hyaluronidase (rHuPH20) in studies 160603 or 160902. | Posted | Number | Percentage of participants | Throughout entire study period for 160603 (1 year 11 months) and 160902 (2 years 11 months) |
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| Secondary | 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 | Safety Analysis Data Set | Posted | Number | Number of 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. |
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| Secondary | 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 | Safety Analysis Data Set | Posted | Number | Number of 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. |
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| Secondary | 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. | Safety Analysis Data Set | Posted | Number | Number of 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. |
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| Secondary | 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 | Safety Analysis Data Set | Posted | Number | Number of AEs per participant | 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. |
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| Secondary | 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) | Safety Analysis Data Set | Posted | Number | Number of AEs per participant | 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. |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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) | Safety Analysis Data Set | Posted | Number | Number of AEs per participant | 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. |
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| Secondary | 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 | Safety Analysis Data Set | Posted | Number | Number of AEs per 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. | Infusions | Infusions |
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| Secondary | 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) | Safety Analysis Data Set | Posted | Number | Number of AEs per 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. | Infusions | Infusions |
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| Secondary | 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) | Safety Analysis Data Set | Posted | Number | Number of AEs per 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. | Infusions | Infusions |
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| Secondary | 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. | Safety Analysis Data Set | Posted | Number | Number of AEs per participant | 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. |
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| Secondary | 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. | Safety Analysis Data Set | Posted | Number | Number of AEs per 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. | Infusions | Infusions |
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| Secondary | 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. | Safety Analysis Data Set | Posted | Number | Number of AEs per participant | 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. |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Safety Analysis Data Set | Posted | Number | Number of AEs per 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. | Infusions | Infusions |
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| Secondary | Percentage of Infusions Associated With One or More Local AEs (Including and Excluding Infections), at Any Time During the Study | Safety Analysis Set | Posted | Number | Percentage of infusions | 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. | Infusions | Infusions |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | IGSC, 10% - rHuPH20 | Participants treated with subcutaneous (SC) administration of Immune Globulin Subcutaneous Solution (IGSC), 10% after SC administration of recombinant human hyaluronidase (rHuPH20). | 9 | 63 | 60 | 63 | ||
| EG001 | Safety Follow-up - IGSC, 10% or IGIV, 10% Only | All participants were included in the Safety Follow-up. Safety Follow-up occurred after discontinuation of treatment with recombinant human hyaluronidase (rHuPH20) and included participants who had been treated with intravenous administration of Immune Globulin Intravenous (Human) (IGIV), 10% only throughout the study (e.g. had never received rHuPH20 in this study). At Safety Follow-up, the decision for treatment with either subcutaneous (SC) administration of Immune Globulin Subcutaneous (Human) (IGSC), 10% or IV administration of IGIV, 10% was at the discretion of the investigator and participant. Note: IGIV, 10% is the same product as IGSC, 10%. | 3 | 51 | 45 | 51 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Aortic Valve Incompetence | Cardiac disorders |
| |||
| Atrial Fibrillation | Cardiac disorders |
| |||
| Cardiac Failure Congestive | Cardiac disorders |
| |||
| Appendicitis | Infections and infestations |
| |||
| Cellulitis | Infections and infestations |
| |||
| Cryptosporidiosis Infection | Infections and infestations |
| |||
| Pneumonia Pseudomonas Aeruginosa | Infections and infestations |
| |||
| Femur Fracture | Injury, poisoning and procedural complications |
| |||
| Toxicity to Various Agents | Injury, poisoning and procedural complications |
| |||
| Spinal Meningeal Cyst | Nervous system disorders |
| |||
| Transient Ischaemic Attack | Nervous system disorders |
| |||
| Mental Status Changes | Psychiatric disorders |
| |||
| Cystocele | Reproductive system and breast disorders |
| |||
| Vaginal Prolapse | Reproductive system and breast disorders |
| |||
| Chronic Obstructive Pulmonary Disease | Respiratory, thoracic and mediastinal disorders |
| |||
| Adhesiolysis | Surgical and medical procedures |
| |||
| Hypertension | Vascular disorders |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphadenopathy | Blood and lymphatic system disorders |
| |||
| Tachycardia | Cardiac disorders |
| |||
| Abdominal Pain | Gastrointestinal disorders |
| |||
| Abdominal Pain Upper | Gastrointestinal disorders |
| |||
| Apthous Stomatitis | Gastrointestinal disorders |
| |||
| Constipation | Gastrointestinal disorders |
| |||
| Diarrhoea | Gastrointestinal disorders |
| |||
| Gastrooesophageal Reflux | Gastrointestinal disorders |
| |||
| Nausea | Gastrointestinal disorders |
| |||
| Vomiting | Gastrointestinal disorders |
| |||
| Asthenia | General disorders |
| |||
| Fatigue | General disorders |
| |||
| Infusion Site Discomfort | General disorders |
| |||
| Infusion Site Erythema | General disorders |
| |||
| Infusion site Pain | General disorders |
| |||
| Infusion Site Pruritus | General disorders |
| |||
| Oedema Peripheral | General disorders |
| |||
| Pain | General disorders |
| |||
| Pyrexia | General disorders |
| |||
| Bronchitis | Infections and infestations |
| |||
| Cellulitis | Infections and infestations |
| |||
| Chronic Sinusitis | Infections and infestations |
| |||
| Gastroenteritis | Infections and infestations |
| |||
| Gastroenteritis Viral | Infections and infestations |
| |||
| Influenza | Infections and infestations |
| |||
| Nasopharyngitis | Infections and infestations |
| |||
| Oral Herpes | Infections and infestations |
| |||
| Pharyngitis | Infections and infestations |
| |||
| Sinusitis | Infections and infestations |
| |||
| Upper Respiratory Tract Infection | Infections and infestations |
| |||
| Urinary Tract Infection | Infections and infestations |
| |||
| Viral Upper Respiratory Tract Infection | Infections and infestations |
| |||
| Contusion | Injury, poisoning and procedural complications |
| |||
| Excoriation | Injury, poisoning and procedural complications |
| |||
| Procedural Pain | Injury, poisoning and procedural complications |
| |||
| Blood Creatine Phosphokinase Increased | Investigations |
| |||
| Arthralgia | Musculoskeletal and connective tissue disorders |
| |||
| Back Pain | Musculoskeletal and connective tissue disorders |
| |||
| Myalgia | Musculoskeletal and connective tissue disorders |
| |||
| Dizziness | Nervous system disorders |
| |||
| Headache | Nervous system disorders |
| |||
| Migraine | Nervous system disorders |
| |||
| Anxiety | Psychiatric disorders |
| |||
| Depression | Psychiatric disorders |
| |||
| Insomnia | Psychiatric disorders |
| |||
| Asthma | Respiratory, thoracic and mediastinal disorders |
| |||
| Cough | Respiratory, thoracic and mediastinal disorders |
| |||
| Dyspnoea | Respiratory, thoracic and mediastinal disorders |
| |||
| Epistaxis | Respiratory, thoracic and mediastinal disorders |
| |||
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders |
| |||
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders |
| |||
| Dermititis Contact | Skin and subcutaneous tissue disorders |
| |||
| Pruritus | Skin and subcutaneous tissue disorders |
| |||
| Hypertension | Vascular disorders |
|
Baxalta's agreements with PIs may vary per requirements of individual PI, but contain common elements. For this study, PIs are restricted from independently publishing results until the earlier of the primary multicenter publication or 12 months after study completion. Baxalta requires a review of results communications (e.g., for confidential information) ≥45 days prior to submission or communication. Baxalta may request an additional delay of ≤60 days eg, for intellectual property protection.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.com |
| ID | Term |
|---|---|
| D000081207 | Primary Immunodeficiency Diseases |
| ID | Term |
|---|---|
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D012847 | Single Person |
| D012449 | Safety |
| D013812 | Therapeutics |
| ID | Term |
|---|---|
| D017533 | Marital Status |
| D005191 | Family Characteristics |
| D003710 | Demography |
| D011154 | Population Characteristics |
| D012959 | Socioeconomic Factors |
| D000056 | Accident Prevention |
| D000059 | Accidents |
| D011634 | Public Health |
| D004778 | Environment and Public Health |
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