A Clinical Study of Intravenous Immunoglobulin

Immunologic Deficiency Syndromes Clinical Trial

— IGIV  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00468273
• Other study ID #: GAM-PID-03-US
• Status: Completed
• Phase: Phase 3
• First received: May 1, 2007
• Last updated: August 7, 2014
• Start date: November 2006
• Est. completion date: August 2009

Study information

• Verified date: August 2014
• Source: FFF Enterprises
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: August 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 75 Years

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Immunologic Deficiency Syndromes

Intervention

Drug:
• Immune Globulin Intravenous (Human) Omr-IgG-am IGIV
IGIV infusions of 300-900 mg/kg every 3 or 4 weeks

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario
Canada	University of Toronto	Toronto	Ontario
United States	1st Allergy and Clinical Research Center	Centennial	Colorado
United States	Rush University Medical Center	Chicago	Illinois
United States	Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	Optimed Research, LLC	Columbus	Ohio
United States	Pediatric Allergy Immunology Associates	Dallas	Texas
United States	Allergy, Asthma and Immunology Clinic PA	Irving	Texas
United States	Mattel Children's Hospital of UCLA	Los Angeles	California
United States	Allergy Associates of the Palm Beaches	North Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
FFF Enterprises	OMRIX Biopharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (8)

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. — View Citation

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. Erratum in: Ann Allergy Asthma Immunol. 2006 Mar;96(3):504. — View Citation

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. — View Citation

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. Erratum in: BMJ 1994 Apr 2;308(6933):913. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	The number of hospitalizations and days of hospitalization per subject per year for PID related infections		during treatment with study drug-1 year	Yes
Secondary	The incidence of infections other than acute serious bacterial infections		during treatment with study drug-1 year	No
Secondary	The number of days lost from work/school/usual activities		during treatment with study drug-1 year	Yes
Secondary	The number of days of antibiotic therapy (prophylactic and treatment)		during treatment with study drug-1 year	No
Secondary	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	No
Secondary	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	No
Secondary	The number of patients whose trough IgG levels fall below the target of 500 mg/dL at any time will be recorded.		one year	No
Secondary	All adverse events that occur during the study regardless of the investigator's assessment of the relationship to the investigational product.		one year	Yes
Secondary	Laboratory assessments on blood and urine samples including direct antiglobulin (Coomb's) tests.		one year	Yes
Secondary	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	Yes