Clinical trial NCT00468273: A Clinical Study of Intravenous Immunoglobulin
Official title: A Clinical Study of Immune Globulin Intravenous (Human) Omr-IgG-am IGIV in Subjects With Primary Immune Deficiency Diseases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Immunologic Deficiency Syndromes
Keywords: Deficiency Syndromes, Antibody
Antibody Deficiency Syndrome
Bruton's agammaglobulinemia
Common Variable Immune Deficiency
Hyper IgM syndromes
Lead sponsor: FFF Enterprises
Sponsor class: INDUSTRY
Collaborators: name: OMRIX Biopharmaceuticals
First posted: 2007-05-02
Enrollment: 57
Sex: ALL
Minimum age (years): 3
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief 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.

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.

Eligibility 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 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.

Primary outcomes:
measure: Incidence of acute serious bacterial infections
timeFrame: one year
Secondary outcomes:
measure: The number of hospitalizations and days of hospitalization per subject per year for PID related infections
timeFrame: during treatment with study drug-1 year
measure: The incidence of infections other than acute serious bacterial infections
timeFrame: during treatment with study drug-1 year
measure: The number of days lost from work/school/usual activities
timeFrame: during treatment with study drug-1 year
measure: The number of days of antibiotic therapy (prophylactic and treatment)
timeFrame: during treatment with study drug-1 year
measure: 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.
timeFrame: after 5th or 6th study infusion
measure: Trough levels of IgG subclasses and specific antibodies will be estimated for each subject in the pharmacokinetic study at defined intervals.
timeFrame: Months 0, 5, 9, 12
measure: The number of patients whose trough IgG levels fall below the target of 500 mg/dL at any time will be recorded.
timeFrame: one year
measure: All adverse events that occur during the study regardless of the investigator's assessment of the relationship to the investigational product.
timeFrame: one year
measure: Laboratory assessments on blood and urine samples including direct antiglobulin (Coomb's) tests.
timeFrame: one year
measure: 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).
timeFrame: Months -1, 14, 16
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Mattel Children's Hospital of UCLA
state: California
city: Centennial
country: United States
facility: 1st Allergy and Clinical Research Center
state: Colorado
city: North Palm Beach
country: United States
facility: Allergy Associates of the Palm Beaches
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Optimed Research, LLC
state: Ohio
city: Dallas
country: United States
facility: Pediatric Allergy Immunology Associates
state: Texas
city: Irving
country: United States
facility: Allergy, Asthma and Immunology Clinic PA
state: Texas
city: Toronto
country: Canada
facility: University of Toronto
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children
name: Chaim Roifman, MD
role: STUDY_CHAIR
affiliation: Mattel Children's Hospital of UCLA
name: Robert Roberts, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 1st Allergey and Clinical Research Center
name: Isaac R Melamed, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rush Universitity Medical Centre
name: James Moy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Hospital for Sick Children
name: Eyal Grunebaum, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Toronto
name: Gordan L Sussman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rainbow Babies and Children's Hospital
name: Akhilesh Chouksey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Allergy Associates of the Palm Beaches
name: Mark Stein, MD
role: PRINCIPAL_INVESTIGATOR
name: Richard L Wasserman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Allergy, Asthma and Immunology Clinic PA
name: Daniel Suez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Optimed Research LLC
name: Don McNeil, MD
role: PRINCIPAL_INVESTIGATOR
References:
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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. doi: 10.1016/s1081-1206(10)61142-8. No abstract available.
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. doi: 10.1136/bmj.308.6928.581. No abstract available.
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. doi: 10.1016/s0140-6736(87)90494-6.
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. doi: 10.7326/0003-4819-135-3-200108070-00008.
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. doi: 10.1016/s1567-5769(03)00134-6.
citation: 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.