Clinical trial NCT01581593: Efficacy and Safety Study of Kedrion IVIG 10% to Treat Subjects With Primary Immunodeficiency (PID)
Official title: Multicenter, Open-label, Historically Controlled, Phase III Study to Assess the Efficacy, Tolerability, Safety and Pharmacokinetics of Kedrion IVIG 10% in Adult and Pediatric Subjects With Primary Immunodeficiency (PID).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Immunodeficiency
Agammaglobulinemia
Hypogammaglobulinemia
Antibody Deficiency
Keywords: Primary Immunodeficiency
PID
Agammaglobulinemia
Hypogammaglobulinemia
Antibody deficiency
Lead sponsor: Kedrion S.p.A.
Sponsor class: INDUSTRY
First posted: 2012-04-20
Enrollment: 45
Sex: ALL
Minimum age (years): 2
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether Kedrion IVIG 10% (an immunoglobulin solution) is effective in treating Primary Immunodeficiency (PID).

Detailed description: People with primary immunodeficiency diseases (PID) have a defective immune system and experience recurrent protozoal, bacterial, fungal and viral infections. Antibody deficiencies make up the largest group of PIDs.

The standard care for patients with PID is replacement immunoglobulin (a class of antibodies) solution. Prophylactic treatment with intravenous immunoglobulin (IVIG) solution has been shown to increase the time free from serious infection.

Kedrion IVIG 10% is a new preparation of an immunoglobulin G (IgG) solution. Kedrion IVIG 10% will be given by IV infusion to all study participants. The data collected will help determine whether Kedrion IVIG 10% is suitable for treating PID subjects.

Eligibility criteria: Inclusion Criteria:

* Confirmed clinical diagnosis of a Primary Immunodeficiency Disease
* Male or female, ages 2 to 70 years
* Received 300-900 mg/kg of a licensed IVIG therapy at 21 or 28 day intervals for at least 3 months prior to this study
* 2 documented IgG trough levels of ≥ 5 g/L are obtained at two infusion cycles (21 or 28 days) within 12 months (one must be within 6 months) prior to study enrolment
* Non-pregnant females of child-bearing potential who agree to use adequate birth control during the study
* Subject is willing to comply with the protocol
* Authorization to access personal health information.
* Signed the informed consent form and a child assent form, if appropriate.
* If currently participating in a clinical trial with another experimental IVIG may be enrolled if they have received stable IVIG therapy for at least 3 infusion cycles prior to receiving Kedrion IVIG 10% and all inclusion and exclusion criteria are satisfied
* If currently participating in a trial of SCIG can be enrolled if they are switched to IVIG for three infusion cycles (21 or 28 days) prior to enrolment in this study

Exclusion Criteria:

* Has secondary immunodeficiency.
* Newly diagnosed and has not been treated with immunoglobulin or has been diagnosed with dysgammaglobulinemia or isolated IgG subclass deficiency.
* Has a history of repeated reactions or hypersensitivity to IVIG or other injectable forms of IgG.
* Has a history of thrombotic events defined by at least 1 event in subject's lifetime.
* Has IgA deficiency and is known to have antibodies to IgA.
* Has received blood products other than human albumin or human immunoglobulin within 12 months prior to enrolment.
* Has significant protein losing enteropathy, nephrotic syndrome or lymphangiectasia.
* Has an acute infection as documented by culture or diagnostic imaging and/or a body temperature exceeding 38.5 °C (101.3 °F) within 7 days prior to screening
* Has a known history or is positive at enrolment for human immunodeficiency virus (HIV) type 1 by NAT, hepatitis B virus (HBsAg and NAT), hepatitis C virus (by NAT), or hepatitis A virus (by NAT).
* Has levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5 times of the upper limit of normal for the laboratory designated for the study.
* Has an implanted venous access device
* Has profound anemia or persistent severe neutropenia (≤ 1000 neutrophils per mm3)or lymphopenia of less than 500 cells per microliter.
* Has a severe chronic condition such as renal failure (creatinine concentration \> 2.0 times the upper limit of normal) with proteinuria, congestive heart failure (New York Heart Association III/IV), cardiomyopathy, cardiac arrhythmia associated with thromboembolic events (e.g. atrial fibrillation), unstable or advanced ischemic heart disease, hyperviscosity, or any other condition that the investigator believes is likely to interfere with evaluation of the study drug or with satisfactory conduct of the trial.
* Has a history of a malignant disease other than properly treated carcinoma in situ of the cervix or basal cell or squamous cell carcinoma of the skin within 24 months prior to enrolment.
* Has history of epilepsy or multiple episodes of migraine (defined as at least one episode within 6 months of enrolment) not completely controlled by medication.
* Is receiving steroids (oral or parenteral daily dose of ≥ 0.15 mg/kg/day of prednisone or equivalent) OR other immunosuppressive drugs or chemotherapy.
* Females who are pregnant, breast feeding or planning a pregnancy during the course of the study. Women who become pregnant during the study will be withdrawn from the study.
* Has participated in another clinical study within 3 weeks prior to study enrolment.

Primary outcomes:
measure: Incidence of Acute, Serious Bacterial Infections in the Total ITT Population.
timeFrame: 13 months
Secondary outcomes:
measure: Infections Other Than Acute, Serious Bacterial Infections (ASBIs) in the Total ITT Population.
timeFrame: 13 months
measure: Days Out of Work/School/Daycare Due to Infection in the Total ITT Population.
timeFrame: 13 months
measure: Days Unable to Perform Normal Daily Activities Due to Infection in the Total ITT Population.
timeFrame: 13 months
measure: Days on Therapeutic Antibiotics in the Total ITT Population.
timeFrame: 13 months
measure: Days of Unscheduled Visits to Physicians in the Total ITT Population.
timeFrame: 13 months
measure: Number of Hospitalizations Due to Infection in ITT Population.
timeFrame: 13 months
measure: Days of Hospitalization Due to Infection in the Total ITT Population.
timeFrame: 13 months
measure: Yearly Hospitalization Rate Due to Infection in the Total ITT Population.
timeFrame: 13 months
measure: Yearly Hospitalization Duration Due to Infection in the Total ITT Population.
timeFrame: 13 months
measure: Distribution of All-cause Hospitalizations in the Total ITT Population.
timeFrame: 13 months
measure: Duration of All-cause Hospitalizations
timeFrame: 13 months
measure: Distribution of Fever Episodes in the Total ITT Population.
timeFrame: 13 months
measure: Duration of Fever Episodes
timeFrame: 13 months
measure: IgG Trough Levels at Steady State in the Total ITT Population.
timeFrame: 13 months
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: North Palm Beach
country: United States
facility: Allergy Associates of the Palm Beaches
state: Florida
city: Atlanta
country: United States
facility: Family Allergy & Asthma Center, PC
state: Georgia
city: Chicago
country: United States
facility: Rush University
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinics
state: Iowa
city: Plymouth
country: United States
facility: Midwest Immunology Clinic
state: Minnesota
city: Rochester
country: United States
facility: AAIR Research Center
state: New York
city: Columbus
country: United States
facility: Optimed Research, LTD
state: Ohio
city: Dallas
country: United States
facility: Dallas Allergy Immunology Research
state: Texas
city: Dallas
country: United States
facility: AARA Research Center
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University Health Systems
state: Virginia
city: Spokane
country: United States
facility: Marycliff Allergy Specialists
state: Washington
city: Toronto
country: Canada
facility: Gordon Sussman Clinical Research Inc.
state: Ontario
city: Toronto
country: Canada
facility: Pediatric & Adult Allergy & Clinical Immunology
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: Kedrion SpA
name: Mirella Calcinai, MD
role: STUDY_DIRECTOR
References: