A Clinical Study of Intravenous Immunoglobulin (IGIV)

A Clinical Study of Immune Globulin Intravenous (Human) Omr-IgG-am IGIV in Subjects With Primary Immune Deficiency Diseases

The purpose of this study is to measure the pharmacokinetics, efficacy and safety of Immune Globulin Intravenous (Human) [IGIV], 5% Solution Omr-IgG-am™ in patients with primary immunodeficiency diseases.

Study Overview

• Status: Completed
• Conditions: Immunologic Deficiency Syndromes
• Intervention / Treatment: Drug: Immune Globulin Intravenous (Human) Omr-IgG-am IGIV

Detailed Description

This is an open label, single-arm, prospective, multi-center, uncontrolled Phase III clinical study to evaluate the efficacy, pharmacokinetics and safety of Omr-IgG-am™ in patients with primary immunodeficiency diseases.

Approximately 50 subjects will be enrolled for 16 Months:

screening- 1 month treatment-12 months follow-up-3 months

Subjects will be infused every 21 to 28 days according to their previous IVIG treatment schedule. Subjects treated every 28 days will receive 13 study IGIV infusions. Subjects treated every 21 days will receive 17 study IGIV infusions.

We will record the incidence of acute infections, especially acute serious bacterial infections, during the year each subjet is on study.

We will record the incidence of adverse events that occur during each infusion and up to 48 hours after each infusion.

At the time the study is explained to the subjects, each investigator will ask all subjects whose body weight is above 37 kg (or greater as defined by local standards) about their willingness to participate in the pharmacokinetic (PK) portion of the study. This will involve 4 additional visits after the 5th or 6th study IGIV infusion in order to draw blood samples for analysis.

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1X8
      • The Hospital for Sick Children
    • Toronto, Ontario, Canada, M4V1R2
      • University of Toronto
• United States
  • California
    • Los Angeles, California, United States, 90095-1752
      • Mattel Children's Hospital of UCLA
  • Colorado
    • Centennial, Colorado, United States, 80112
      • 1st Allergy and Clinical Research Center
  • Florida
    • North Palm Beach, Florida, United States, 33408
      • Allergy Associates of the Palm Beaches
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Rainbow Babies and Children's Hospital
    • Columbus, Ohio, United States, 43235
      • Optimed Research, LLC
  • Texas
    • Dallas, Texas, United States, 75230
      • Pediatric Allergy Immunology Associates
    • Irving, Texas, United States, 75230
      • Allergy, Asthma and Immunology Clinic PA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 75 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

The following list is incomplete. A complete list is in the protocol.

Inclusion Criteria:

• Ages 3 to 75 years and weigh at least 27 kg.
• Confirmed clinical diagnosis of a Primary Immune Deficiency disease including hypogammaglobulinemia, preferably with documented antibody deficiency, or agammaglobulinemia.
• Has been receiving licensed IGIV for at least 3 months prior to this study.
• Trough IgG levels, dose of IGIV, and treatment intervals for the last 2 consecutive licensed IGIV treatments must be documented.
• The subject or legal guardian has signed the informed consent form. If appropriate, the subject has signed a child assent form.
• The subject or legal representative has signed the HIPAA declaration.

Exclusion Criteria:

• Subjects with isolated IgG subclass deficiency or specific antibody deficiency without hypogammaglobulinemia will not be eligible.
• The subject has a history of hypersensitivity or persistent or repeated adverse reactions to human immunoglobulin.
• The subject has selective IgA deficiency, history of reaction to products containing IgA, or is known to have antibodies to IgA.
• The subject is currently participating, or has participated within the previous 30 days, in another clinical study of an investigational product or device.
• The subject is pregnant or is nursing. Women of childbearing potential must agree to using a method of contraception.
• The subject has had an acute bacterial infection within 28 days of screening.
• The subject is seropositive for any of the following at screening:
• Antibodies to HIV 1&2
• Antibodies to HCV
• HbsAg
• The subject, at screening, has alanine aminotransferase (ALT) levels greater than 2.5 times the upper limit of normal.
• The subject has severe renal impairment.
• The subject has a history of DVT, thrombotic or thrombic complications of IGIV therapy.
• The subject suffers from any acute or chronic medical condition that, in the opinion of the investigator, may interfere with the conduct of the study.
• The subject has an acquired medical condition known to cause secondary immune deficiency or otherwise increase the subject's risk of infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intravenous Immune Globulin; Subjects with primary humoral immunodeficiency	Drug: Immune Globulin Intravenous (Human) Omr-IgG-am IGIV; IGIV infusions of 300-900 mg/kg every 3 or 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of acute serious bacterial infections	Acute serious bacterial infections are defined in The FDA(CBER) Guidance for industry for studies of IGIV to support marketing of IGIV as replacement therapy for primary humoral immunodeficiency (June, 2008).	one year

Secondary Outcome Measures

Outcome Measure	Time Frame
The number of hospitalizations and days of hospitalization per subject per year for PID related infections	during treatment with study drug-1 year
The incidence of infections other than acute serious bacterial infections	during treatment with study drug-1 year
The number of days lost from work/school/usual activities	during treatment with study drug-1 year
The number of days of antibiotic therapy (prophylactic and treatment)	during treatment with study drug-1 year
Pharmacokinetic parameters of IgG subclasses and specific antibodies will be determined in at least 20 patients: AUC0-t, Cmax, Tmax, t1/2, Vd and elimination rate constants.	after 5th or 6th study infusion
Trough levels of IgG subclasses and specific antibodies will be estimated for each subject in the pharmacokinetic study at defined intervals.	Months 0, 5, 9, 12
The number of patients whose trough IgG levels fall below the target of 500 mg/dL at any time will be recorded.	one year
All adverse events that occur during the study regardless of the investigator's assessment of the relationship to the investigational product.	one year
Laboratory assessments on blood and urine samples including direct antiglobulin (Coomb's) tests.	one year
Markers of blood borne virus infections at baseline and up to 3 months after the last infusion i.e. HIV (serology), HCV (serology and NAT), HBV (HbsAg).	Months -1, 14, 16

Collaborators and Investigators

• Sponsor: FFF Enterprises
• Collaborators: OMRIX Biopharmaceuticals
• Investigators: Principal Investigator: Robert Roberts, MD, Mattel Children's Hospital of UCLA; Principal Investigator: Isaac R Melamed, MD, 1st Allergey and Clinical Research Center; Principal Investigator: James Moy, MD, Rush Universitity Medical Centre; Principal Investigator: Eyal Grunebaum, MD, The Hospital for Sick Children; Principal Investigator: Gordan L Sussman, MD, University of Toronto; Principal Investigator: Akhilesh Chouksey, MD, Rainbow Babies and Children's Hospital; Principal Investigator: Mark Stein, MD, Allergy Associates of the Palm Beaches; Principal Investigator: Richard L Wasserman, MD; Principal Investigator: Daniel Suez, MD, Allergy, Asthma and Immunology Clinic PA; Principal Investigator: Don McNeil, MD, Optimed Research LLC

Publications and helpful links

General Publications

• Ten RM. Primary immunodeficiencies. Mayo Clin Proc. 1998 Sep;73(9):865-72. doi: 10.4065/73.9.865.
• Bonilla FA, Geha RS. 12. Primary immunodeficiency diseases. J Allergy Clin Immunol. 2003 Feb;111(2 Suppl):S571-81. doi: 10.1067/mai.2003.86. Erratum In: J Allergy Clin Immunol. 2003 Aug;112(2):267.
• Bonilla FA, Bernstein IL, Khan DA, Ballas ZK, Chinen J, Frank MM, Kobrynski LJ, Levinson AI, Mazer B, Nelson RP Jr, Orange JS, Routes JM, Shearer WT, Sorensen RU; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. Practice parameter for the diagnosis and management of primary immunodeficiency. Ann Allergy Asthma Immunol. 2005 May;94(5 Suppl 1):S1-63. doi: 10.1016/s1081-1206(10)61142-8. No abstract available. Erratum In: Ann Allergy Asthma Immunol. 2006 Mar;96(3):504.
• Chapel HM. Consensus on diagnosis and management of primary antibody deficiencies. Consensus Panel for the Diagnosis and Management of Primary Antibody Deficiencies. BMJ. 1994 Feb 26;308(6928):581-5. doi: 10.1136/bmj.308.6928.581. No abstract available. Erratum In: BMJ 1994 Apr 2;308(6933):913.
• Roifman CM, Levison H, Gelfand EW. High-dose versus low-dose intravenous immunoglobulin in hypogammaglobulinaemia and chronic lung disease. Lancet. 1987 May 9;1(8541):1075-7. doi: 10.1016/s0140-6736(87)90494-6.
• Eijkhout HW, van Der Meer JW, Kallenberg CG, Weening RS, van Dissel JT, Sanders LA, Strengers PF, Nienhuis H, Schellekens PT; Inter-University Working Party for the Study of Immune Deficiencies. The effect of two different dosages of intravenous immunoglobulin on the incidence of recurrent infections in patients with primary hypogammaglobulinemia. A randomized, double-blind, multicenter crossover trial. Ann Intern Med. 2001 Aug 7;135(3):165-74. doi: 10.7326/0003-4819-135-3-200108070-00008.
• Roifman CM, Schroeder H, Berger M, Sorensen R, Ballow M, Buckley RH, Gewurz A, Korenblat P, Sussman G, Lemm G. Comparison of the efficacy of IGIV-C, 10% (caprylate/chromatography) and IGIV-SD, 10% as replacement therapy in primary immune deficiency. A randomized double-blind trial. Int Immunopharmacol. 2003 Sep;3(9):1325-33. doi: 10.1016/s1567-5769(03)00134-6.
• Berger M. A history of immune globulin therapy, from the Harvard crash program to monoclonal antibodies. Curr Allergy Asthma Rep. 2002 Sep;2(5):368-78. doi: 10.1007/s11882-002-0069-z.

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (ACTUAL): May 1, 2009
• Study Completion (ACTUAL): August 1, 2009

Study Registration Dates

• First Submitted: May 1, 2007
• First Submitted That Met QC Criteria: May 1, 2007
• First Posted (ESTIMATE): May 2, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): August 11, 2014
• Last Update Submitted That Met QC Criteria: August 7, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: Deficiency Syndromes, Antibody; Antibody Deficiency Syndrome; Bruton's agammaglobulinemia; Common Variable Immune Deficiency; Hyper IgM syndromes
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Disease; Syndrome; Immunologic Deficiency Syndromes; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: GAM-PID-03-US; NCT00468273 (REGISTRY: ClinicalTrials.gov)