A Clinical Study of the PK, Efficacy and Safety of Omr-IgG-am IGIV in Subjects With Primary Immune Deficiency Diseases - Full Text View

Purpose

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.

Condition	Intervention	Phase
Immunologic Deficiency Syndromes	Drug: Intravenous Immune Globulin	Phase 3

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	A Clinical Study of the Pharmacokinetics, Efficacy and Safety of Immune Globulin Intravenous (Human) Omr-IgG-am IGIV in Subjects With Primary Immune Deficiency Diseases

Resource links provided by NLM:

Genetics Home Reference related topics: common variable immune deficiency complement factor I deficiency X-linked agammaglobulinemia X-linked hyper IgM syndrome

MedlinePlus related topics: Bacterial Infections

Drug Information available for: Rhophylac Rho(D) Immune Globulin

U.S. FDA Resources

Further study details as provided by FFF Enterprises:

Primary Outcome Measures:

Incidence of acute serious bacterial infections [ Time Frame: one year ] [ Designated as safety issue: No ]
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).
IgG pharmacokinetics [ Time Frame: after 5th or 6th infusion ] [ Designated as safety issue: No ]
Incidence of adverse events that occur during or within 1 hour, 24 hours and 72 hours following infusion [ Time Frame: Any time after treatment with study IGIV ] [ Designated as safety issue: Yes ]
The upper one-sided 95% confidence limit of temporally associated adverse events to be less than 40%.

Secondary Outcome Measures:

The number of hospitalizations and days of hospitalization per subject per year for PID related infections [ Time Frame: during treatment with study drug-1 year ] [ Designated as safety issue: Yes ]
The incidence of infections other than acute serious bacterial infections [ Time Frame: during treatment with study drug-1 year ] [ Designated as safety issue: No ]
The number of days lost from work/school/usual activities [ Time Frame: during treatment with study drug-1 year ] [ Designated as safety issue: Yes ]
The number of days of antibiotic therapy (prophylactic and treatment) [ Time Frame: during treatment with study drug-1 year ] [ Designated as safety issue: No ]
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. [ Time Frame: after 5th or 6th study infusion ] [ Designated as safety issue: No ]
Trough levels of IgG subclasses and specific antibodies will be estimated for each subject in the pharmacokinetic study at defined intervals. [ Time Frame: Months 0, 5, 9, 12 ] [ Designated as safety issue: No ]
The number of patients whose trough IgG levels fall below the target of 500 mg/dL at any time will be recorded. [ Time Frame: one year ] [ Designated as safety issue: No ]
All adverse events that occur during the study regardless of the investigator's assessment of the relationship to the investigational product. [ Time Frame: one year ] [ Designated as safety issue: Yes ]
Laboratory assessments on blood and urine samples including direct antiglobulin (Coomb's) tests. [ Time Frame: one year ] [ Designated as safety issue: Yes ]
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). [ Time Frame: Months -1, 14, 16 ] [ Designated as safety issue: Yes ]

Enrollment:	57
Study Start Date:	November 2006
Study Completion Date:	August 2009
Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Intravenous Immune Globulin Subjects with primary humoral immunodeficiency	Drug: Intravenous Immune Globulin IGIV infusions of 300-900 mg/kg every 3 or 4 weeks Other Name: Omr-IgG-am

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 immunodificiency 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 actute 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.

Eligibility

Ages Eligible for Study:	3 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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 aminotranferase (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 thrombo-embolic 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00468273

Locations

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

Sponsors and Collaborators

FFF Enterprises

OMRIX Biopharmaceuticals

Investigators

Study Chair:	Chaim Roifman, MD	The Hospital for Sick Children
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

More Information

Publications:

Ten RM. Primary immunodeficiencies. Mayo Clin Proc. 1998 Sep;73(9):865-72. Review.

Bonilla FA, Geha RS. 12. Primary immunodeficiency diseases. J Allergy Clin Immunol. 2003 Feb;111(2 Suppl):S571-81. Review. 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. 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. Review. 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.

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.

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.

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.

Responsible Party:	FFF Enterprises
ClinicalTrials.gov Identifier:	NCT00468273 History of Changes
Other Study ID Numbers:	GAM-PID-03-US
Study First Received:	May 1, 2007
Last Updated:	March 5, 2013
Health Authority:	United States: Food and Drug Administration Canada: Health Canada

Keywords provided by FFF Enterprises:

Deficiency Syndromes, Antibody
Antibody Deficiency Syndrome
Bruton's agammaglobulinemia
Common Variable Immune Deficiency
Hyper IgM syndromes

Additional relevant MeSH terms:

Deficiency Diseases
Immunologic Deficiency Syndromes
Malnutrition
Nutrition Disorders
Immune System Diseases
Antibodies

Immunoglobulins
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 16, 2013