Primary Immunodeficiency Diseases (PID)Phase 2/3NCT00546871
Comparison of Intravenous and Subcutaneous Administration of IGIV, 10% in Primary Immunodeficiency (PID) Subjects
A Phase 2/3 study testing Immune Globulin Intravenous (Human), 10% in people with Primary Immunodeficiency Diseases (PID), run by Baxalta now part of Shire at 9 sites in United States.
Trial summary
The purpose of this study is to evaluate the tolerability of IGIV, 10% given subcutaneously and the pharmacokinetics of immunoglobulin G (IgG) following subcutaneous (SC) treatment with IGIV, 10% in subjects with primary immunodeficiency (PID) disorders. Read more about this study
- Who is it for?
- Ages 24 months and older
- Conditions the study is for
- Primary Immunodeficiency Diseases (PID)
- What is being tested?
- Immune Globulin Intravenous (Human), 10%
- Type of treatment
- Injection or infusion
- How many people
- 49 participants
- Where
- 9 sitesUnited States
- Study dates
- 3 Oct 2007to 1 Sep 2009
- 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 24 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Written informed consent obtained from either the subject or the subject's legally acceptable representative prior to any study-related procedures and study product administration
- Diagnosis of a PID disorder as defined by World Health Organization criteria (IUIS Scientific Committee, Primary immunodeficiency diseases. Report of an IUIS Scientific Committee. Clin Exp Immunol. 1999) for which the subject has been receiving a regular regimen of IV immunoglobulin infusions every 21 ± 3 days or 28 ± 3 days or a regular SC immunoglobulin treatment at 1 to 2 week intervals over a period of at least 3 months pre-study at a dose of 300-800 mg/kg BW/4 weeks
- Subjects are aged 2 years or older
- Subjects have a serum trough level of IgG > 4.5 g/L at the last documented determination
- A negative serum pregnancy test for any female subject who is of childbearing potential
- Female subjects of childbearing potential agree to practice birth control measures for the duration of the study
Who cannot join
- Subjects positive at enrollment for one or more of the following: Hepatitis B surface antigen (HBsAg), PCR for hepatitis C virus (HCV), PCR for human immunodeficiency virus (HIV) Type 1
- Subjects with levels of alanine amino transferase (ALT) or aspartate amino transferase (AST) > 2.5 times the upper limit of normal for the testing laboratory
- Subjects with neutropenia (defined as an absolute neutrophil count [ANC] <= 500/mm3)
- Subjects with serum creatinine levels greater than 1.5 times the upper limit of normal for age and gender
- Subjects with a malignancy other than adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
- Subjects with a history of thrombotic episodes (deep vein thrombosis, myocardial infarction, cerebrovascular accident)
Show all 14Show fewer
- Subjects with abnormal protein loss (protein losing enteropathy, nephritic syndrome, severe lung disease)
- Subjects with anemia that would preclude phlebotomy for laboratory studies
- Subjects who received any blood or blood product other than an IGIV, SC immunoglobulin, immune serum globulin (ISG) preparation, or albumin within the 6 months prior to study enrollment
- Subjects with an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IGIV, SC immunoglobulin and/or ISG infusions
- Subjects with IgA deficiency and known anti IgA antibodies
- Subjects receiving antibiotic therapy for the treatment of infection within 7 days prior to enrollment
- Subjects participating in another clinical study involving an investigational product or device within 28 days prior to study enrollment
- Subjects with bleeding disorders or who are on anti-coagulation therapy
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Study site
Atlanta, Georgia
Study site
Centennial, Colorado
Study site
Cleveland, Ohio
Study site
Dallas, Texas
Study site
Durham, North Carolina
Study site
Galveston, Texas
Study site
Los Angeles, California
Study site
Milwaukee, Wisconsin
Study site
North Palm Beach, Florida
About this study
Official title: Tolerability and Pharmacokinetic Comparison of Immune Globulin Intravenous (Human) 10% (IGIV, 10%) Administered Intravenously or Subcutaneously in Subjects With Primary Immunodeficiency Diseases
The purpose of this study is to evaluate the tolerability of IGIV, 10% given subcutaneously and the pharmacokinetics of immunoglobulin G (IgG) following subcutaneous (SC) treatment with IGIV, 10% in subjects with primary immunodeficiency (PID) disorders.
- Conditions
- Primary Immunodeficiency Diseases (PID)
- Being tested
- Immune Globulin Intravenous (Human), 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.
Immune Globulin Intravenous (Human), 10%Drug
Intravenous administration in Study Part 1, subcutaneous administration in Study Parts 2 and 3
What is being measured
The primary outcome is the main question the study is designed to answer.
Ratio of Area Under the Concentration Curve (AUC 0-τ)/Week Following IV Administration to SC Administration of IGIV, 10% at an Adjusted/Individual Adapted Dose (Part 3b), Expressed as a Percentage
Expressed as (AUC_SC/AUC_IV) * 100
Measured: Week 12 (IV) and week 32 or 33 (SC)
Bioavailability (Trough Levels) of IgG After Administration of IGIV, 10%, in Participants Aged 2 to <12 Years.
Administration of IGIV, 10%: - Part 1 = IV administration (IV) - Parts 2, 3a, 3b = SC administration (SC)
Measured: Baseline; at each 3 or 4-week study visit in Study Part 1; at Visits 1, 5, and 9 in Study Part 2; at Visits 1, and 5 in Study Part 3a; at Visits 1, 5, and 9 in Study Part 3b; and at the end-of-study evaluation
Percentage of Participants in Full Safety Data Set (FSDS) Who Had Any Infusion for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of participants for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Measured: Throughout study (1 year and 9 months)
Percentage of Participants Naïve to SC Administration of Immunoglobulins (SNSC) Who Had Any Infusion for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped.
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of participants for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Measured: Throughout study (1 year and 9 months)
Percentage of Participants With Prior Experience With Subcutaneous Administration of Immunoglobulins (SESC) Who Had Any Infusion for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of participants for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Measured: Throughout study (1 year and 9 months)
Percentage of Infusions in FSDS for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of infusions for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Measured: Throughout study (1 year and 9 months)
Percentage of Infusions in SNSC for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of infusions for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Measured: Throughout study (1 year and 9 months)
Percentage of Infusions in SESC for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of infusions for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Measured: Throughout study (1 year and 9 months)
Secondary outcomes (35)
Study Part 1 (IV): Maximum Plasma Concentration (C-max)
Maximal immune globulin concentration after infusion
Measured: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.
Study Part 1 (IV): Minimum Plasma Concentration (C-min)
Minimal immune globulin concentration after infusion
Measured: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.
Study Part 1 (IV): Weight-adjusted Clearance
Computed as weight-adjusted dose divided by total AUC
Measured: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.
Study Part 1 (IV): Terminal Half-life
Computed from the regression slope in the terminal phase of the model (the slope is biphasic). Terminal half life is the time it takes for the plasma concentration or the amount of immunoglobulin in the body to be reduced by 50%during the terminal phase.
Measured: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.
Study Part 2 (Subcutaneous (SC)): Maximum Plasma Concentration (C-max)
Maximal immune globulin concentration after infusion
Measured: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Study Part 2 (SC): Time to Maximum Immune Globulin Concentration (T-max)
Time to reach C-max
Measured: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Study Part 2 (SC): Minimum Plasma Concentration (C-min)
Minimal immune globulin concentration after infusion
Measured: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Study Part 2 (SC): Weight-adjusted Clearance
Computed as weight-adjusted dose divided by total AUC
Measured: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Study Part 3B: Maximum Plasma Concentration (C-max)
Maximal immune globulin concentration after infusion
Measured: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Study Part 3B: Time to Maximum Immune Globulin Concentration (T-max)
Time to reach C-max
Measured: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Study Part 3B: Minimum Plasma Concentration (C-min)
Minimal immune globulin concentration after infusion
Measured: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Study Part 3B: Area Under the Curve (AUC)
The AUC between adjacent infusions was calculated by the trapezoidal rule. Linear interpolation/extrapolation was used to calculate the AUC for the exact duration of the infusion intervals (21 or 28 days for IV administration and 7 days for SC administration). To allow for comparisons between Study Parts 1, 2 and 3b, AUC(0-τ) was standardized for the infusion intervals (3 or 4 weeks vs. 1 week).
Measured: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Study Part 3B: Weight-adjusted Clearance
Computed as weight-adjusted dose divided by total AUC
Measured: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Trough Levels of IgG After Administration of IGIV, 10%, in Participants 12 Years and Older
Part 1: IgG trough levels measured at each IV infusion day (every 3rd or 4th week depending on schedule/frequency of participants for a total of 12 weeks) Part 2: IgG trough levels measured at weeks 1, 5 and 9 (of a total of 12 weeks) Part 3a: IgG trough levels measured at weeks 1 and 5 (of a total of 6 weeks) Part 3b: IgG trough levels measured at weeks 1, 5, 9 and 12 (of a total of 12 weeks)
Measured: Baseline; at each 3 or 4-week study visit in Study Part 1; at Visits 1, 5, and 9 in Study Part 2; at Visits 1, and 5 in Study Part 3a; at Visits 1, 5, and 9 in Study Part 3b; and at the end-of-study evaluation
Trough Levels of Antibody to Haemophilus Influenzae In All Study Participants
Trough levels for IV and SC Treatment in Study Parts 1, 2, 3a and 3b.
Measured: Baseline; at each 3 or 4-week study visit in Study Part 1; at Visits 1, 5, and 9 in Study Part 2; at Visit 1 in Study Part 3a; at Visits 1, 5, and 9 in Study Part 3b; at Visit 1 in the Study Extension Part; and at the end-of-study evaluation
Trough Levels of Antibody to Hepatitis B in All Study Participants
Trough levels for IV and SC Treatment in Study Parts 1, 2, 3a and 3b.
Measured: Baseline; at each 3 or 4-week study visit in Study Part 1; at Visits 1, 5, and 9 in Study Part 2; at Visit 1 in Study Part 3a; at Visits 1, 5, and 9 in Study Part 3b; at Visit 1 in the Study Extension Part; and at the end-of-study evaluation
Trough Levels of Antibody to Tetanus In All Study Participants
Trough levels for IV and SC Treatment in Study Parts 1, 2, 3a and 3b.
Measured: Baseline; at each 3 or 4-week study visit in Study Part 1; at Visits 1, 5, and 9 in Study Part 2; at Visit 1 in Study Part 3a; at Visits 1, 5, and 9 in Study Part 3b; at Visit 1 in the Study Extension Part; and at the end-of-study evaluation
Number of Anti-Measles Antibody Titers That Were Below or Above the Protective Titer Level
Antibody Titers That Were Below or Above the Protective Titer Level of >1:8 for IV and SC Treatment in Study Parts 1, 2, 3a and 3b. Participants had multiple anti-measles antibody titers measured during the study.
Measured: Baseline; at each 3 or 4-week study visit in Study Part 1; at Visits 1, 5, and 9 in Study Part 2; at Visit 1 in Study Part 3a; at Visits 1, 5, and 9 in Study Part 3b; at Visit 1 in the Study Extension Part; and at the end-of-study evaluation
Annual Infection Rates During Treatment
Annual rate of all infections calculated using a Poisson model to account for different lengths of observation per subject using SAS V9.1.3 procedure GENMOD with allowance for overdispersion by deviance method. Point estimates and likelihood-ratio based 95% confidence intervals were provided. Infections as included in analysis comprised all reported AEs that were coded to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) of infections and infestations, described as an infection by investigator, or for which anti-infective medication was prescribed.
Measured: Throughout the study, 1 year and 9 months
Annual Rate of Acute Serious Bacterial Infections During IV and SC Treatment (FSDS)
Annual rate of validated acute serious bacterial infections was calculated using a Poisson model to account for the different lengths of observation per subject using SAS V9.1.3 procedure GENMOD with an allowance for overdispersion by the deviance method.
Measured: Throughout the study, 1 year and 9 months
Rate of Temporally Associated AEs Per Infusion
Rate of AEs per infusion defined as the total number of all AEs that begin during infusion or within 72 hours of completion of an infusion ("temporally associated") divided by the total number of infusions.
Measured: During Infusion or Within 72 Hours of Completion of Infusions
AEs Deemed/Judged to be Related by the Investigator
Rate of related AEs defined as the total number of AEs determined by the investigator to be related to the study drug that occur at any time during the study divided by the total number of infusions.
Measured: Throughout the study period (1 year and 9 months)
Frequency of Dose Adjustments (If IgG Trough Levels <4.5 g/L)
Frequency of Dose Adjustments Based on IgG Trough Levels <4.5 g/L IgG, if Any, for Each Study Part. Defined/calculated as the number of participants requiring dose adjustments divided by the number of participants, for each respective data set.
Measured: Throughout the study period (1 year and 9 months)
Proportion of Participants Reporting ≥1 Temporally Associated Moderate or Severe AEs
Proportion of Participants Reporting 1 or More Moderate or Severe AEs That Begin During Infusion or Within 72 Hours of Completion of an Infusion.
Measured: During Infusion or Within 72 Hours of Completion of Infusions
Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (FSDS)
Seriousness and causality are abbreviated below as: Seriousness: Serious Adverse Event= SAE, non-Serious Adverse Event= non-SAE Causality: possibly or probably related= R, not related= NR
Measured: Throughout entire study (1 year and 9 months)
Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (FSDS)
Seriousness and causality are abbreviated below as: Seriousness: Serious Adverse Event= SAE, non-Serious Adverse Event= non-SAE Causality: possibly or probably related= R, not related= NR Rate of AEs defined as the number of AEs categorized by MedDRA preferred terms, seriousness, severity, and causality divided by the number of infusions.
Measured: Throughout entire study (1 year and 9 months)
Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SNSC -All Ages)
Seriousness and causality are abbreviated below as: Seriousness: Serious Adverse Event= SAE, non-Serious Adverse Event= non-SAE Causality: possibly or probably related= R, not related= NR
Measured: Throughout entire study (1 year and 9 months)
Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SNSC- All Ages)
Seriousness and causality are abbreviated below as: Seriousness: Serious Adverse Event= SAE, non-Serious Adverse Event= non-SAE Causality: possibly or probably related= R, not related= NR Rate of AEs defined as the number of AEs categorized by MedDRA preferred terms, seriousness, severity, and causality divided by the number of infusions.
Measured: Throughout entire study (1 year and 9 months)
Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SESC)
Seriousness and causality are abbreviated below as: Seriousness: Serious Adverse Event= SAE, non-Serious Adverse Event= non-SAE Causality: possibly or probably related= R, not related= NR
Measured: Throughout entire study (1 year and 9 months)
Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SESC)
Seriousness and causality are abbreviated below as: Seriousness: Serious Adverse Event= SAE, non-Serious Adverse Event= non-SAE Causality: possibly or probably related= R, not related= NR Rate of AEs defined as the number of AEs categorized by MedDRA preferred terms, seriousness, severity, and causality divided by the number of infusions.
Measured: Throughout entire study (1 year and 9 months)
Percentage of Infusions Associated With ≥1 AE Related to the Study Drug
Measured: Throughout the study period (1 year and 9 months)
Percentage of Infusions Associated With ≥1 AEs That Begin During Infusion or Within 72 Hours of Completion of Infusion
Measured: During Infusion or Within 72 Hours of Completion of Infusions
Percentage of Infusions Associated With ≥1 AE Excluding Infections That Begin During Infusion or Within 72 Hours of Completion of Infusion.
Measured: During Infusion or Within 72 Hours of Completion of Infusions
Percentage of Infusions Associated With ≥1 Systemic AE Excluding Infections That Begin During Infusion or Within 72 Hours of Completion of Infusion.
Measured: During Infusion or Within 72 Hours of Completion of Infusions
Percentage of Infusions Associated With ≥1 Local AE Excluding Infections That Begin During Infusion or Within 72 Hours of Completion of Infusion.
Measured: During Infusion or Within 72 Hours of Completion of Infusions
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2007 (estimated)
- Study start3 Oct 2007
- Primary completion1 Jul 2009
- Study completion1 Sep 2009
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 (5)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 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 49 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
- NCT00546871
- Sponsor's protocol ID
- 160601
- Status last verified
- Apr 2021
- First submitted
- 18 Oct 2007
- Last updated
- 19 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Neu AM, Warady BA, Furth SL, Lederman HM, Fivush BA. Antibody levels to diphtheria, tetanus, and rubella in infants vaccinated while on PD: a Study of the Pediatric Peritoneal Dialysis Study Consortium. Adv Perit Dial. 1997;13:297-9.
PubMed 9440877Leibl H, Engl W, Melamed I, Stein M, Wasserman RL, Berger M, Schiff RI. IGIV-10% Infused Intravenously And Subcutaneously To Subjects With Primary Immunodeficiency Diseases - Comparison Of Pharmacokinetic Properties. Poster presentation at AAAAI 2009.
Schiff RI, Leibl H, Engl W. Pharmacokinetic properties of Gammagard Liquid 10% (KIOVIG) administered intravenously and subcutaneously to patients with primary immunodeficiency diseases. Clin Exp Immunol. 154 (Suppl. 1):132, 2008
Wasserman RL, Melamed I, Kobrynski L, Strausbaugh SD, Stein MR, Sharkhawy M, Engl W, Leibl H, Sobolevsky L, Gelmont D, Schiff RI, Grossman WJ. Efficacy, safety, and pharmacokinetics of a 10% liquid immune globulin preparation (GAMMAGARD LIQUID, 10%) administered subcutaneously in subjects with primary immunodeficiency disease. J Clin Immunol. 2011 Jun;31(3):323-31. doi: 10.1007/s10875-011-9512-z. Epub 2011 Mar 22.
PubMed 21424824Wasserman 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
- Tolerability and Pharmacokinetic Comparison of Immune Globulin Intravenous (Human) 10% (IGIV, 10%) Administered Intravenously or Subcutaneously in Subjects With Primary Immunodeficiency Diseases
- ClinicalTrials.gov ID
- NCT00546871
- Acronym / sponsor ID
- 160601
- Conditions
- Primary Immunodeficiency Diseases (PID)
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Baxalta now part of ShireIndustry (pharma, biotech, devices)
- Study start
- 3 Oct 2007 (actual)
- Primary completion
- 1 Jul 2009 (actual)
- Study completion
- 1 Sep 2009 (actual)
- First posted
- 19 Oct 2007 (estimated)
- Results
- Posted 23 Aug 2012
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 this study is to evaluate the tolerability of IGIV, 10% given subcutaneously and the pharmacokinetics of immunoglobulin G (IgG) following subcutaneous (SC) treatment with IGIV, 10% in subjects with primary immunodeficiency (PID) disorders.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 24 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Written informed consent obtained from either the subject or the subject's legally acceptable representative prior to any study-related procedures and study product administration
- Diagnosis of a PID disorder as defined by World Health Organization criteria (IUIS Scientific Committee, Primary immunodeficiency diseases. Report of an IUIS Scientific Committee. Clin Exp Immunol. 1999) for which the subject has been receiving a regular regimen of IV immunoglobulin infusions every 21 ± 3 days or 28 ± 3 days or a regular SC immunoglobulin treatment at 1 to 2 week intervals over a period of at least 3 months pre-study at a dose of 300-800 mg/kg BW/4 weeks
- Subjects are aged 2 years or older
- Subjects have a serum trough level of IgG > 4.5 g/L at the last documented determination
- A negative serum pregnancy test for any female subject who is of childbearing potential
Key exclusion criteria (14 listed)
- Subjects positive at enrollment for one or more of the following: Hepatitis B surface antigen (HBsAg), PCR for hepatitis C virus (HCV), PCR for human immunodeficiency virus (HIV) Type 1
- Subjects with levels of alanine amino transferase (ALT) or aspartate amino transferase (AST) > 2.5 times the upper limit of normal for the testing laboratory
- Subjects with neutropenia (defined as an absolute neutrophil count [ANC] <= 500/mm3)
- Subjects with serum creatinine levels greater than 1.5 times the upper limit of normal for age and gender
- Subjects with a malignancy other than adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
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 Intravenous (Human), 10%Intravenous administration in Study Part 1, subcutaneous administration in Study Parts 2 and 3 | Drug | – |
Primary outcome
Ratio of Area Under the Concentration Curve (AUC 0-τ)/Week Following IV Administration to SC Administration of IGIV, 10% at an Adjusted/Individual Adapted Dose (Part 3b), Expressed as a Percentage
Time frame: Week 12 (IV) and week 32 or 33 (SC)
Expressed as (AUC_SC/AUC_IV) * 100
Bioavailability (Trough Levels) of IgG After Administration of IGIV, 10%, in Participants Aged 2 to <12 Years.
Time frame: Baseline; at each 3 or 4-week study visit in Study Part 1; at Visits 1, 5, and 9 in Study Part 2; at Visits 1, and 5 in Study Part 3a; at Visits 1, 5, and 9 in Study Part 3b; and at the end-of-study evaluation
Administration of IGIV, 10%: - Part 1 = IV administration (IV) - Parts 2, 3a, 3b = SC administration (SC)
Percentage of Participants in Full Safety Data Set (FSDS) Who Had Any Infusion for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Time frame: Throughout study (1 year and 9 months)
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of participants for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Percentage of Participants Naïve to SC Administration of Immunoglobulins (SNSC) Who Had Any Infusion for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped.
Time frame: Throughout study (1 year and 9 months)
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of participants for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Percentage of Participants With Prior Experience With Subcutaneous Administration of Immunoglobulins (SESC) Who Had Any Infusion for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Time frame: Throughout study (1 year and 9 months)
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of participants for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Percentage of Infusions in FSDS for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Time frame: Throughout study (1 year and 9 months)
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of infusions for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Percentage of Infusions in SNSC for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Time frame: Throughout study (1 year and 9 months)
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of infusions for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
Percentage of Infusions in SESC for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Time frame: Throughout study (1 year and 9 months)
Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of infusions for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs
35 secondary outcomes
Study Part 1 (IV): Maximum Plasma Concentration (C-max)
Time frame: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.
Study Part 1 (IV): Minimum Plasma Concentration (C-min)
Time frame: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.
Study Part 1 (IV): Weight-adjusted Clearance
Time frame: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.
Study Part 1 (IV): Terminal Half-life
Time frame: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.
Study Part 2 (Subcutaneous (SC)): Maximum Plasma Concentration (C-max)
Time frame: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Study Part 2 (SC): Time to Maximum Immune Globulin Concentration (T-max)
Time frame: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Study Part 2 (SC): Minimum Plasma Concentration (C-min)
Time frame: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Study Part 2 (SC): Weight-adjusted Clearance
Time frame: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Study Part 3B: Maximum Plasma Concentration (C-max)
Time frame: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Study Part 3B: Time to Maximum Immune Globulin Concentration (T-max)
Time frame: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Study Part 3B: Minimum Plasma Concentration (C-min)
Time frame: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Study Part 3B: Area Under the Curve (AUC)
Time frame: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Study Part 3B: Weight-adjusted Clearance
Time frame: Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.
Trough Levels of IgG After Administration of IGIV, 10%, in Participants 12 Years and Older
Time frame: Baseline; at each 3 or 4-week study visit in Study Part 1; at Visits 1, 5, and 9 in Study Part 2; at Visits 1, and 5 in Study Part 3a; at Visits 1, 5, and 9 in Study Part 3b; and at the end-of-study evaluation
Trough Levels of Antibody to Haemophilus Influenzae In All Study Participants
Time frame: Baseline; at each 3 or 4-week study visit in Study Part 1; at Visits 1, 5, and 9 in Study Part 2; at Visit 1 in Study Part 3a; at Visits 1, 5, and 9 in Study Part 3b; at Visit 1 in the Study Extension Part; and at the end-of-study evaluation
Trough Levels of Antibody to Hepatitis B in All Study Participants
Time frame: Baseline; at each 3 or 4-week study visit in Study Part 1; at Visits 1, 5, and 9 in Study Part 2; at Visit 1 in Study Part 3a; at Visits 1, 5, and 9 in Study Part 3b; at Visit 1 in the Study Extension Part; and at the end-of-study evaluation
Trough Levels of Antibody to Tetanus In All Study Participants
Time frame: Baseline; at each 3 or 4-week study visit in Study Part 1; at Visits 1, 5, and 9 in Study Part 2; at Visit 1 in Study Part 3a; at Visits 1, 5, and 9 in Study Part 3b; at Visit 1 in the Study Extension Part; and at the end-of-study evaluation
Number of Anti-Measles Antibody Titers That Were Below or Above the Protective Titer Level
Time frame: Baseline; at each 3 or 4-week study visit in Study Part 1; at Visits 1, 5, and 9 in Study Part 2; at Visit 1 in Study Part 3a; at Visits 1, 5, and 9 in Study Part 3b; at Visit 1 in the Study Extension Part; and at the end-of-study evaluation
Annual Infection Rates During Treatment
Time frame: Throughout the study, 1 year and 9 months
Annual Rate of Acute Serious Bacterial Infections During IV and SC Treatment (FSDS)
Time frame: Throughout the study, 1 year and 9 months
Rate of Temporally Associated AEs Per Infusion
Time frame: During Infusion or Within 72 Hours of Completion of Infusions
AEs Deemed/Judged to be Related by the Investigator
Time frame: Throughout the study period (1 year and 9 months)
Frequency of Dose Adjustments (If IgG Trough Levels <4.5 g/L)
Time frame: Throughout the study period (1 year and 9 months)
Proportion of Participants Reporting ≥1 Temporally Associated Moderate or Severe AEs
Time frame: During Infusion or Within 72 Hours of Completion of Infusions
Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (FSDS)
Time frame: Throughout entire study (1 year and 9 months)
Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (FSDS)
Time frame: Throughout entire study (1 year and 9 months)
Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SNSC -All Ages)
Time frame: Throughout entire study (1 year and 9 months)
Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SNSC- All Ages)
Time frame: Throughout entire study (1 year and 9 months)
Number of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SESC)
Time frame: Throughout entire study (1 year and 9 months)
Rate of All AEs Categorized by MedDRA Preferred Terms, Seriousness, Severity, and Causality (SESC)
Time frame: Throughout entire study (1 year and 9 months)
Percentage of Infusions Associated With ≥1 AE Related to the Study Drug
Time frame: Throughout the study period (1 year and 9 months)
Percentage of Infusions Associated With ≥1 AEs That Begin During Infusion or Within 72 Hours of Completion of Infusion
Time frame: During Infusion or Within 72 Hours of Completion of Infusions
Percentage of Infusions Associated With ≥1 AE Excluding Infections That Begin During Infusion or Within 72 Hours of Completion of Infusion.
Time frame: During Infusion or Within 72 Hours of Completion of Infusions
Percentage of Infusions Associated With ≥1 Systemic AE Excluding Infections That Begin During Infusion or Within 72 Hours of Completion of Infusion.
Time frame: During Infusion or Within 72 Hours of Completion of Infusions
Percentage of Infusions Associated With ≥1 Local AE Excluding Infections That Begin During Infusion or Within 72 Hours of Completion of Infusion.
Time frame: During Infusion or Within 72 Hours of Completion of Infusions
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.
- Background: PubMed 9440877Neu AM, Warady BA, Furth SL, Lederman HM, Fivush BA. Antibody levels to diphtheria, tetanus, and rubella in infants vaccinated while on PD: a Study of the Pediatric Peritoneal Dialysis Study Consortium. Adv Perit Dial. 1997;13:297-9.
- Results publicationLeibl H, Engl W, Melamed I, Stein M, Wasserman RL, Berger M, Schiff RI. IGIV-10% Infused Intravenously And Subcutaneously To Subjects With Primary Immunodeficiency Diseases - Comparison Of Pharmacokinetic Properties. Poster presentation at AAAAI 2009.
- Results publicationSchiff RI, Leibl H, Engl W. Pharmacokinetic properties of Gammagard Liquid 10% (KIOVIG) administered intravenously and subcutaneously to patients with primary immunodeficiency diseases. Clin Exp Immunol. 154 (Suppl. 1):132, 2008
- Results publication: PubMed 21424824Wasserman RL, Melamed I, Kobrynski L, Strausbaugh SD, Stein MR, Sharkhawy M, Engl W, Leibl H, Sobolevsky L, Gelmont D, Schiff RI, Grossman WJ. Efficacy, safety, and pharmacokinetics of a 10% liquid immune globulin preparation (GAMMAGARD LIQUID, 10%) administered subcutaneously in subjects with primary immunodeficiency disease. J Clin Immunol. 2011 Jun;31(3):323-31. doi: 10.1007/s10875-011-9512-z. Epub 2011 Mar 22.
- 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
9 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 Intravenous (Human), 10% in people with Primary Immunodeficiency Diseases (PID), run by Baxalta now part of Shire at 9 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 6 inclusion and 14 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 9 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 23 Aug 2012). 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?
Ratio of Area Under the Concentration Curve (AUC 0-τ)/Week Following IV Administration to SC Administration of IGIV, 10% at an Adjusted/Individual Adapted Dose (Part 3b), Expressed as a Percentage (time frame: Week 12 (IV) and week 32 or 33 (SC)). The study lists 8 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 NCT00546871, which also lists 5 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.