Efficacy and Safety Study of Kedrion IVIG 10% to Treat Subjects With Primary Immunodeficiency (PID)

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

Detailed Description
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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.

Official Title
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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).

Conditions
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Primary Immunodeficiency, Agammaglobulinemia, Hypogammaglobulinemia, Antibody Deficiency

Intervention / Treatment
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* Biological: Kedrion IVIG 10%


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Kedrion IVIG 10%<br>Kedrion IVIG 10% treatment. | Biological: Kedrion IVIG 10%<br>* Dosage form - Intravenous (IV) infusion of Kedrion IVIG 10%; Dosage - 300 to 900 mg/kg body weight (bw); Frequency - every 21 to 28 days; Treatment duration - 12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Acute, Serious Bacterial Infections in the Total ITT Population. | The incidence of acute serious bacterial infections, e.g. bacterial pneumonia, bacteremia/sepsis, bacterial meningitis, visceral abscess, osteomyelitis/septic arthritis, meeting EMA and FDA criteria. | 13 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infections Other Than Acute, Serious Bacterial Infections (ASBIs) in the Total ITT Population. |  | 13 months | 
| Days Out of Work/School/Daycare Due to Infection in the Total ITT Population. |  | 13 months | 
| Days Unable to Perform Normal Daily Activities Due to Infection in the Total ITT Population. |  | 13 months | 
| Days on Therapeutic Antibiotics in the Total ITT Population. |  | 13 months | 
| Days of Unscheduled Visits to Physicians in the Total ITT Population. |  | 13 months | 
| Number of Hospitalizations Due to Infection in ITT Population. |  | 13 months | 
| Days of Hospitalization Due to Infection in the Total ITT Population. |  | 13 months | 
| Yearly Hospitalization Rate Due to Infection in the Total ITT Population. |  | 13 months | 
| Yearly Hospitalization Duration Due to Infection in the Total ITT Population. |  | 13 months | 
| Distribution of All-cause Hospitalizations in the Total ITT Population. |  | 13 months | 
| Duration of All-cause Hospitalizations |  | 13 months | 
| Distribution of Fever Episodes in the Total ITT Population. |  | 13 months | 
| Duration of Fever Episodes |  | 13 months | 
| IgG Trough Levels at Steady State in the Total ITT Population. |  | 13 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PID, Primary Immunodeficiency, Agammaglobulinemia, Hypogammaglobulinemia, Antibody deficiency