Primary Immunodeficiency Diseases (PID)Phase 2/3NCT01485796
Tolerability and Safety of IGI, 10% With rHuPH20 in PIDD
A Phase 2/3 study testing Immune Globulin Infusion (Human), 10% and Recombinant human hyaluronidase in people with Primary Immunodeficiency Diseases (PID), run by Baxalta now part of Shire at 10 sites in United States.
Trial summary
The purpose of the study is to acquire additional data on safety and tolerability of recombinant human hyaluronidase (rHuPH20) facilitated subcutaneous treatment of Immune Globulin Infusion (Human), 10% (IGI, 10%) and to assess the mode of product administration. 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?
- Immune Globulin Infusion (Human), 10% and Recombinant human hyaluronidase
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 10 sitesUnited States
- Study dates
- 29 Dec 2011to 1 Jan 2013
- Phase
- Phase 2/3
- 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
- Subject must have a documented diagnosis of a form of primary humoral immunodeficiency involving a defect in antibody formation and requiring gammaglobulin replacement, as defined according to the IUIS Scientific Committee 2009 and by diagnostic criteria according to Conley et al. The diagnosis must be reviewed by the Medical Director prior to enrollment.
- Subject is 2 years or older at the time of screening.
- Written informed consent is obtained from either the subject or the subject's legally authorized representative prior to any study-related procedures and study product administration.
- Subject has been receiving a consistent dose of immunoglobulin G (IgG) with a non-Baxter product (Gammunex administered IV, Hizentra, or Privigen), administered in compliance with the respective product information, for a period of at least 3 months prior to screening. The average minimum pre-study dose over that interval was equivalent to 300 mg/kg BW/4 weeks and a maximum dose equivalent to 600 mg/kg BW/4 weeks at a dosing frequency as follows:
- For IV treatment prior to the study: at mean intervals of 3 or 4 weeks (+/- 3 days) or
- For SC treatment prior to the study: at mean intervals of approximately 1 or 2 weeks (+/- 2 days).
Show all 10Show fewer
- Subject has a serum trough level of IgG > 5 g/L at screening.
- Subject has not had a serious bacterial infection within the 3 months prior to screening.
- If female of childbearing potential, subject presents with a negative pregnancy test and agrees to employ adequate birth control measures for the duration of the study.
- Subject is willing and able to comply with the requirements of the protocol.
Who cannot join
- Subject has a known history of or is positive at screening for one or more of the following: hepatitis B surface antigen (HBsAg), polymerase chain reaction (PCR) for hepatitis C virus (HCV), PCR for human immunodeficiency virus (HIV) Type 1/2.
- Abnormal laboratory values at screening meeting any one of the following criteria (abnormal tests may be repeated once to determine if they are persistent):
- Persistent alanine aminotransferase (ALT) and aspartate amino transferase (AST) > 2.5 times the upper limit of normal for the testing laboratory
- Persistent severe neutropenia (defined as an absolute neutrophil count [ANC] <= 500/mm3).
- Subject has creatinine clearance (CLcr) value that is <60% of normal for age and gender either measured, or calculated according to a gender-specific formula provided in the study protocol.
- Subject has been diagnosed with or has a malignancy (other than adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix), unless the disease-free period prior to screening exceeds 5 years
Show all 24Show fewer
- Subject is receiving anti-coagulation therapy or has a history of thrombotic episodes (including deep vein thrombosis, myocardial infarction, cerebrovascular accident, pulmonary embolism) within 12 months prior to screening or a history of thrombophilia.
- Subject has abnormal protein loss (protein losing enteropathy, nephrotic syndrome).
- Subject has anemia that would preclude phlebotomy for laboratory studies, according to standard practice at the site.
- Subject has an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IV immunoglobulin, SC immunoglobulin, and/or Immune Serum Globulin (ISG) infusions.
- Subject has immunoglobulin A (IgA) deficiency (IgA less than 0.07g/L) and known anti IgA antibodies.
- Subject has a known allergy to hyaluronidase.
- Subject is on preventative (prophylactic) systemic antibacterial antibiotics at doses sufficient to treat or prevent bacterial infections, and cannot stop these antibiotics at the time of screening.
- Subject has active infection and is receiving antibiotic therapy for the treatment of infection at the time of screening.
- Subject has a bleeding disorder or a platelet count less than 20,000/μL, or who, in the opinion of the investigator, would be at significant risk of increased bleeding or bruising as a result of SC therapy.
- Subject has total protein > 9 g/dL or myeloma, or macroglobulinemia (IgM) or paraproteinemia.
- Women of childbearing potential meeting any one of the following criteria:
- Subject presents with a positive pregnancy test
- Subject is breast feeding
- Subject intends to begin nursing during the course of the study
- Subject does not agree to employ adequate birth-control measures (e.g. intrauterine device, diaphragm or condom [for male partner] with spermicidal jelly or foam, or birth control pills/patches) throughout the course of the study.
- Subject has participated in another clinical study and has been exposed to an investigational product (IP) or device within 30 days prior to study enrollment (exception: treatment with immunoglobulin pre-study).
- Subject is scheduled to participate in another (non-Baxter) clinical study involving an IP or device during the course of the study.
- Subject has severe dermatitis that would preclude adequate sites for safe product administration.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
University of California, Irvine
Irvine, California, 92697
Allergy, Asthma & Immunology Clinic PA
Irving, Texas, 75063
Winthrop Allergy and Immunology
Mineola, New York, 11501
LSU Health Sciences Center & Children´s Hospital
New Orleans, Louisiana, 70118
Allergy Associates of the Palm Beaches, PA
North Palm Beach, Florida, 33408
Oklahoma Institute of Allergy & Asthma Clinical Research
Oklahoma City, Oklahoma, 73131
Midlands Pediatrics PC
Papillion, Nebraska, 68046
Allergy and Clinical Immunology Associates
Pittsburgh, Pennsylvania, 15241
Midwest Immunology
Plymouth, Minnesota, 55446
IMMUNOe International Research Centers
Thornton, Colorado, 80233
About this study
Official title: Tolerability, Safety and Administration Mode Evaluation of Recombinant Human Hyaluronidase (rHuPH20) Facilitated Subcutaneous Treatment With Immune Globulin Infusion (Human), 10% in Subjects With Primary Immunodeficiency Diseases (PIDD)
The purpose of the study is to acquire additional data on safety and tolerability of recombinant human hyaluronidase (rHuPH20) facilitated subcutaneous treatment of Immune Globulin Infusion (Human), 10% (IGI, 10%) and to assess the mode of product administration.
Following a discussion with the FDA at the end of July 2012, all participants still active in the study stopped treatment with rHuPH20 to assure safety of the participants participating in the study and went into a safety follow-up.
During this safety follow-up period, participants underwent treatment with the licensed product IGI, 10% (Gammagard Liquid). The intravenous or subcutaneous administration route was at the discretion of the participant and the investigator.
- Conditions
- Primary Immunodeficiency Diseases (PID)
- Being tested
- Immune Globulin Infusion (Human), 10%, Recombinant human hyaluronidase
- Keywords
- PIDD
- 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.
Immune Globulin Infusion (Human), 10%Biological
Also called IGI, 10%
Subcutaneous administration will be used in Study Epochs 1 and 2.
Recombinant human hyaluronidaseBiological
Also called rHuPH20
rHuPH20 will be administered subcutaneously (SC) immediately before each SC IGI, 10% infusion, through the same needle, at a rate of 1 to 2 mL/min.
| Study group | Role | What they receive |
|---|---|---|
| Epoch 1 and Epoch 2 | Experimental | In Study Epoch 1 PIDD patients that are already on intravenous treatment or subcutaneous treatment will be enrolled and treated with IGI, 10% and rHuPH20 subcutaneously, with a short dose/interval ramp-up (Epoch 1) consisting of one 1-week dose and interval and one 2-week dose and interval. The ramp-up (Epoch 1) is followed by Epoch 2 which consists of approximately 6 months (24 weeks) of IGI, 10% and rHuPH20 treatment. For subjects pretreated intravenously (IV), this treatment will occur every 3 or 4 weeks (at a 3-week or 4-week dose, respectively), depending on the subject´s previous IV dosing schedule. For subjects pretreated subcutaneously (SC), treatment will also occur every 3 or 4 weeks (at a 3-week or 4-week dose, respectively), at the discretion of the investigator and subject. Receives: Biological: Immune Globulin Infusion (Human), 10%; Biological: Recombinant human hyaluronidase |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Related Systemic Adverse Events (Excluding Infections)
Measured: 7 months (per subject)
Rate of Related Systemic Adverse Events (Excluding Infections) Per Infusion
A point estimate and 95% confidence interval for the rate of related systemic adverse events per infusion was derived using a Poisson model.
Measured: 7 months (per subject)
Secondary outcomes (13)
Proportion of Subjects Who Achieve a Treatment Interval of 3 or 4 Weeks in Epoch 2
Measured: 6 months (per subject)
Proportion of Subjects Who Maintain a Treatment Interval of 3 or 4 Weeks in Epoch 2 for 24 Weeks
Measured: 6 months (per subject)
Number of Related Local Adverse Events (Excluding Infections)
Measured: 7 months (per subject)
Rate of Related Local Adverse Events (Excluding Infections) Per Infusion
A point estimate and 95% confidence interval for the rate of related local adverse events per infusion was derived using a Poisson model.
Measured: 7 months (per subject)
Number of All Related Adverse Events (Excluding Infections)
Measured: 7 months (per subject)
Rate of All Adverse Events (Excluding Infections) Per Infusion
A point estimate and 95% confidence interval for the rate of adverse events per infusion was derived using a Poisson model.
Measured: 7 months (per subject)
Number of Subjects Who Develop Neutralizing Antibodies to rHuPH20
Measured: 7 months (per subject)
Trough Levels of Immunoglobulin G (IgG)
IgG trough levels at the beginning of Study Epoch 1 (previous immunoglobulin treatment) and at the end of Study Epoch 2 were analyzed.
Measured: 7 months (per subject)
Number of Infusions Per Month in Epoch 1 and Epoch 2
Non-parametric descriptive statistics (median, range) are provided.
Measured: 7 months (per subject)
Number of Infusion Sites (Needle Sticks) Per Month in Epoch 1 and Epoch 2
Non-parametric descriptive statistics (median, range) are provided.
Measured: 7 months (per subject)
Duration of Infusion in Epoch 1 and Epoch 2
Non-parametric descriptive statistics (median, range) are provided.
Measured: 7 months (per subject)
Maximum Infusion Rate in Epoch 1 and Epoch 2
Non-parametric descriptive statistics (median, range) are provided.
Measured: 7 months (per subject)
Number of Weeks to Reach Final 3 or 4-week Dose Interval
Non-parametric descriptive statistics (median, range) are provided.
Measured: 7 months (per subject)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2011 (estimated)
- Study start29 Dec 2011
- Primary completion1 Jan 2013
- Study completion1 Jan 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.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 54 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
- NCT01485796
- Sponsor's protocol ID
- 161101
- Status last verified
- Apr 2021
- First submitted
- 2 Dec 2011
- Last updated
- 19 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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
- Tolerability, Safety and Administration Mode Evaluation of Recombinant Human Hyaluronidase (rHuPH20) Facilitated Subcutaneous Treatment With Immune Globulin Infusion (Human), 10% in Subjects With Primary Immunodeficiency Diseases (PIDD)
- ClinicalTrials.gov ID
- NCT01485796
- Acronym / sponsor ID
- 161101
- Conditions
- Primary Immunodeficiency Diseases (PID)
- Keywords
- PIDD
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Baxalta now part of ShireIndustry (pharma, biotech, devices)
- Study start
- 29 Dec 2011 (actual)
- Primary completion
- 1 Jan 2013 (actual)
- Study completion
- 1 Jan 2013 (actual)
- First posted
- 6 Dec 2011 (estimated)
- Results
- Posted 24 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to acquire additional data on safety and tolerability of recombinant human hyaluronidase (rHuPH20) facilitated subcutaneous treatment of Immune Globulin Infusion (Human), 10% (IGI, 10%) and to assess the mode of product administration.
Following a discussion with the FDA at the end of July 2012, all participants still active in the study stopped treatment with rHuPH20 to assure safety of the participants participating in the study and went into a safety follow-up.
During this safety follow-up period, participants underwent treatment with the licensed product IGI, 10% (Gammagard Liquid). The intravenous or subcutaneous administration route was at the discretion of the participant and the investigator.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Epoch 1 and Epoch 2 | Experimental | Biological: Immune Globulin Infusion (Human), 10%, Biological: Recombinant human hyaluronidaseIn Study Epoch 1 PIDD patients that are already on intravenous treatment or subcutaneous treatment will be enrolled and treated with IGI, 10% and rHuPH20 subcutaneously, with a short dose/interval ramp-up (Epoch 1) consisting of one 1-week dose and interval and one 2-week dose and interval. The ramp-up (Epoch 1) is followed by Epoch 2 which consists of approximately 6 months (24 weeks) of IGI, 10% and rHuPH20 treatment. For subjects pretreated intravenously (IV), this treatment will occur every 3 or 4 weeks (at a 3-week or 4-week dose, respectively), depending on the subject´s previous IV dosing schedule. For subjects pretreated subcutaneously (SC), treatment will also occur every 3 or 4 weeks (at a 3-week or 4-week dose, respectively), at the discretion of the investigator and subject. |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Subject must have a documented diagnosis of a form of primary humoral immunodeficiency involving a defect in antibody formation and requiring gammaglobulin replacement, as defined according to the IUIS Scientific Committee 2009 and by diagnostic criteria according to Conley et al. The diagnosis must be reviewed by the Medical Director prior to enrollment.
- Subject is 2 years or older at the time of screening.
- Written informed consent is obtained from either the subject or the subject's legally authorized representative prior to any study-related procedures and study product administration.
- Subject has been receiving a consistent dose of immunoglobulin G (IgG) with a non-Baxter product (Gammunex administered IV, Hizentra, or Privigen), administered in compliance with the respective product information, for a period of at least 3 months prior to screening. The average minimum pre-study dose over that interval was equivalent to 300 mg/kg BW/4 weeks and a maximum dose equivalent to 600 mg/kg BW/4 weeks at a dosing frequency as follows:
- Subject has a serum trough level of IgG > 5 g/L at screening.
Key exclusion criteria (24 listed)
- Subject has a known history of or is positive at screening for one or more of the following: hepatitis B surface antigen (HBsAg), polymerase chain reaction (PCR) for hepatitis C virus (HCV), PCR for human immunodeficiency virus (HIV) Type 1/2.
- Abnormal laboratory values at screening meeting any one of the following criteria (abnormal tests may be repeated once to determine if they are persistent):
- Subject has creatinine clearance (CLcr) value that is <60% of normal for age and gender either measured, or calculated according to a gender-specific formula provided in the study protocol.
- Subject has been diagnosed with or has a malignancy (other than adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix), unless the disease-free period prior to screening exceeds 5 years
- Subject is receiving anti-coagulation therapy or has a history of thrombotic episodes (including deep vein thrombosis, myocardial infarction, cerebrovascular accident, pulmonary embolism) within 12 months prior to screening or a history of thrombophilia.
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 |
|---|---|---|
| Immune Globulin Infusion (Human), 10%Also: IGI, 10%Subcutaneous administration will be used in Study Epochs 1 and 2. | Biological | Epoch 1 and Epoch 2 |
| Recombinant human hyaluronidaseAlso: rHuPH20rHuPH20 will be administered subcutaneously (SC) immediately before each SC IGI, 10% infusion, through the same needle, at a rate of 1 to 2 mL/min. | Biological | Epoch 1 and Epoch 2 |
Primary outcome
Number of Related Systemic Adverse Events (Excluding Infections)
Time frame: 7 months (per subject)
Rate of Related Systemic Adverse Events (Excluding Infections) Per Infusion
Time frame: 7 months (per subject)
A point estimate and 95% confidence interval for the rate of related systemic adverse events per infusion was derived using a Poisson model.
13 secondary outcomes
Proportion of Subjects Who Achieve a Treatment Interval of 3 or 4 Weeks in Epoch 2
Time frame: 6 months (per subject)
Proportion of Subjects Who Maintain a Treatment Interval of 3 or 4 Weeks in Epoch 2 for 24 Weeks
Time frame: 6 months (per subject)
Number of Related Local Adverse Events (Excluding Infections)
Time frame: 7 months (per subject)
Rate of Related Local Adverse Events (Excluding Infections) Per Infusion
Time frame: 7 months (per subject)
Number of All Related Adverse Events (Excluding Infections)
Time frame: 7 months (per subject)
Rate of All Adverse Events (Excluding Infections) Per Infusion
Time frame: 7 months (per subject)
Number of Subjects Who Develop Neutralizing Antibodies to rHuPH20
Time frame: 7 months (per subject)
Trough Levels of Immunoglobulin G (IgG)
Time frame: 7 months (per subject)
Number of Infusions Per Month in Epoch 1 and Epoch 2
Time frame: 7 months (per subject)
Number of Infusion Sites (Needle Sticks) Per Month in Epoch 1 and Epoch 2
Time frame: 7 months (per subject)
Duration of Infusion in Epoch 1 and Epoch 2
Time frame: 7 months (per subject)
Maximum Infusion Rate in Epoch 1 and Epoch 2
Time frame: 7 months (per subject)
Number of Weeks to Reach Final 3 or 4-week Dose Interval
Time frame: 7 months (per subject)
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.
Related trials for Primary Immunodeficiency Diseases (PID)
RecruitingObservational study
Studies of Disorders With Increased Susceptibility to Fungal Infections
Fungal Infections, Primary Immune Deficiencies
RecruitingObservational study
COVID-19 in PID Survey
Primary Immune Deficiency, COVID
Not yet recruitingPhase 4
A Study of TAK-664 in People With Primary Immunodeficiency Diseases Who Have Not Yet Been Treated With Immunoglobulins
Primary Immunodeficiency Diseases (PID)
RecruitingObservational study
A Database Survey to Evaluate the Safety of Immune Globulin Subcutaneous (Human), 20% Solution in Participants With Primary Immunodeficiency
Primary Immunodeficiency Diseases (PID)
Active, not recruitingPhase 2
A Study to Evaluate Tabelecleucel in Participants With Epstein Barr Virus (EBV) Associated Diseases
Epstein-Barr Virus (EBV)-Associated Diseases, EBV+ Lymphoproliferative Disease With Primary Immunodeficiency (EBV+ PID LPD)
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
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Immune Globulin Infusion (Human), 10% and Recombinant human hyaluronidase in people with Primary Immunodeficiency Diseases (PID), run by Baxalta now part of Shire at 10 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 10 inclusion and 24 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 10 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 24 Apr 2017). 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?
Number of Related Systemic Adverse Events (Excluding Infections) (time frame: 7 months (per subject)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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.