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

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).

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

Study Overview

• Status: Completed
• Conditions: Primary Immunodeficiency; Hypogammaglobulinemia; Agammaglobulinemia; Antibody Deficiency
• Intervention / Treatment: Biological: Kedrion IVIG 10%

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.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1X8
      • The Hospital for Sick Children
    • Toronto, Ontario, Canada, M4V1R2
      • Gordon Sussman Clinical Research Inc.
    • Toronto, Ontario, Canada, M5G1E2
      • Pediatric & Adult Allergy & Clinical Immunology
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • Florida
    • North Palm Beach, Florida, United States, 33408
      • Allergy Associates of the Palm Beaches
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Family Allergy & Asthma Center, PC
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospital and Clinics
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
      • Midwest Immunology Clinic
  • New York
    • Rochester, New York, United States, 14618
      • AAIR Research Center
  • Ohio
    • Columbus, Ohio, United States, 43235
      • Optimed Research, LTD
  • Texas
    • Dallas, Texas, United States, 75231
      • AARA Research Center
    • Dallas, Texas, United States, 75230
      • Dallas Allergy Immunology Research
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University Health Systems
  • Washington
    • Spokane, Washington, United States, 99204
      • Marycliff Allergy Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Kedrion IVIG 10%; Kedrion IVIG 10% treatment.	Biological: Kedrion IVIG 10%; 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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Kedrion S.p.A.
• Investigators: Study Director: Mirella Calcinai, MD, Kedrion SpA

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2012
• Primary Completion (Actual): August 27, 2014
• Study Completion (Actual): August 27, 2014

Study Registration Dates

• First Submitted: April 16, 2012
• First Submitted That Met QC Criteria: April 19, 2012
• First Posted (Estimate): April 20, 2012

Study Record Updates

• Last Update Posted (Actual): February 16, 2021
• Last Update Submitted That Met QC Criteria: January 29, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Primary Immunodeficiency; PID; Hypogammaglobulinemia; Agammaglobulinemia; Antibody deficiency
• Additional Relevant MeSH Terms: Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Blood Protein Disorders; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases; Agammaglobulinemia
• Other Study ID Numbers: KB052

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No