Comparison of Intravenous and Subcutaneous Administration of IGIV, 10% in Primary Immunodeficiency (PID) Subjects

NCT00546871 | Completed Phase 2 Results

• 1 other identifier: 160601
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 9

Brief 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.

Conditions

Primary Immunodeficiency Diseases (PID)

Outcome Measures

Primary Outcomes (8)

• 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

  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)

  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

  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

  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

  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

  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

  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

  Throughout study (1 year and 9 months)

Secondary Outcomes (35)

• Study Part 1 (IV): Maximum Plasma Concentration (C-max)

  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)

  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

  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

  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)

  Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.

Interventions

Immune Globulin Intravenous (Human), 10% DRUG

Intravenous administration in Study Part 1, subcutaneous administration in Study Parts 2 and 3

Eligibility Criteria

• Age: 24 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Baxalta now part of Shire: lead

Study Sites (9)

Unknown Facility

Los Angeles, California, United States

Location

Unknown Facility

Centennial, Colorado, United States

Location

Unknown Facility

North Palm Beach, Florida, United States

Location

Unknown Facility

Atlanta, Georgia, United States

Location

Unknown Facility

Durham, North Carolina, United States

Location

Unknown Facility

Cleveland, Ohio, United States

Location

Unknown Facility

Dallas, Texas, United States

Location

Unknown Facility

Galveston, Texas, United States

Location

Unknown Facility

Milwaukee, Wisconsin, United States

Location

Related Publications (5)

• 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.

  PMID: 9440877 BACKGROUND

• Leibl 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.

  RESULT

• 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

  RESULT

• 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.

  PMID: 21424824 RESULT

• Wasserman RL, Gupta S, Stein M, Rabbat CJ, Engl W, Leibl H, Yel L. Infection rates and tolerability of three different immunoglobulin administration modalities in patients with primary immunodeficiency diseases. Immunotherapy. 2022 Mar;14(4):215-224. doi: 10.2217/imt-2021-0256. Epub 2021 Dec 21.

  PMID: 34931880 DERIVED

MeSH Terms

Conditions

Primary Immunodeficiency Diseases

Interventions

gamma-Globulins

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2007
• First Posted: October 19, 2007
• Study Start: October 3, 2007
• Primary Completion: July 1, 2009
• Study Completion: September 1, 2009
• Last Updated: May 19, 2021
• Results First Posted: August 23, 2012

Record last verified: 2021-04

Locations

US (9)