Pediatric Patients Affected by Primary Immunodeficiency Disease. MedDRA version: 20.0 Level: PT Classification code 10064859 Term: Primary immunodeficiency syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: KIg10
Product Code: KIg10
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: Human Immunoglobulin
Current Sponsor code: KIg10
Concentration unit:
Sponsors
KEDRION S.P.A
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent/assent obtained from the patient and his/her parent(s) or egally acceptable representative indicating that they understand the purpose of and procedures required for the study and are willing to participate in it. 2. Confirmed clinical diagnosis of a PID as defined by 2017 International Union of Immunological Societies (IUIS) Phenotypic Classification for Primary Immunodeficiencies (Bousfiha A, 2018) and The European Society for Immunodeficiencies (ESID) Registry Working Definitions for the Clinical Diagnosis of Inborn Errors of Immunity (Seidel MG at al., 2019) and requiring treatment with IVIg. Documented agammaglobulinemia (defined as the total absence of one or more classes of antibodies) or hypogammaglobulinemia (defined as low levels of one or more classes [ie, at least 2 standard deviations under the mean level per age]). (NOTE: IVIg treatment is generally requested in the absence of IgG independently from whether other antibodies are absent). 3. Male or female, age from 2 up to 16 years and 11 months, at the time of screening, as the patient must be under 18 years (=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Newly diagnosed PID and naïve to IgG replacement therapy. Dysgammaglobulinemia (defined as a deficiency in one or more classes of antibodies, but not severe enough to require substitutive therapy) or isolated IgG subclass deficiency, or profound primary T cell deficiency (defined as the absence or severe reduction of T lymphocytes [CD3+ 2.5 times of the upper limit of normal for the laboratory designated for the study. Using an implanted venous access device. Profound anemia, defined according to the patient's age as shown in table Dallman PR, 1979 or persistent severe neutropenia (= 500 neutrophils per mm3) or persistent lymphopenia of less than 500 cells per microliter. A severe chronic condition such as renal failure, 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. 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 ICF signature. History of pharmacoresistant epilepsy or multiple episodes of migraine (defined as at least 1 episode within 6 months of ICF signature) not controlled by medication. Patient must not be receiving the following medication from at least 30 days prior to ICF signature: Steroids, oral or parenteral, at a daily dose of = 0.15 mg/kg/day of prednisone or equivalent). Other immunosuppressive drugs (including monoclonal antibodies) 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. Participated in another clinical study within 30 days prior to ICF signature. Active drug or alcohol abuse or history of drug or alcohol abuse within the 6 months before screening. Direct relative of an employee of the CRO, the study site, or Kedrion. Previously treated under this protocol. Unable to provide informed consent. Patients with any condition which, in the opinion of the Investigator, might interfere with the evaluation of the study objectives or the patient’s participation in this trial. Patients with Hypersensitivity to the act
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Efficacy Objective To assess the efficacy of KIg10 administered to patients with PID to demonstrate that the rate of acute serious bacterial infections (i.e., the mean number of acute serious bacterial infections per patient-year) is less than 1.0 to provide substantial evidence of efficacy from day 1 to week 51/52. Safety Objective To assess the safety of KIg10 in the overall study population from day 1 to week 51/52. Pharmacokinetic Objectives To assess the distribution, metabolism, and elimination of KIg10, total IgG, IgG subclasses, and antigen-specific IgGs at steady state in PID patients treated at different dosing schedules. To evaluate trough concentrations of total IgG and compare to trough concentrations prior to the study entry.;Secondary Objective: Levels: • Of IgG trough before each infusion and at the study termination visit. • Of IgG subclasses before infusions 1, 5, 9, and 13 for the 28-day infusion schedule and at infusions 1, 7, 11, and 17 for the 21-day infusion schedule. • Of Anti-tetanus toxoid, anti-pneumococcal capsular polysaccharide, anti Haemophilus influenza, and anti-measles antibodies before infusions 1, 5, 9, and 13 for the 28-day infusion schedule and before infusions 1, 7, 11, and 17 for the 21-day infusion schedule. Occurrence and duration of any infection other than acute serious bacterial infections, of fever episodes, of overall hospitalization, of hospitalization due to infection, of patients on antibiotics for the treatment of any kind of infections from day 1 to week 51/52. The missed days of work/school/other major activities due to infections, from day 1 to week 51/52. QoL using the PedsQL™ questionnaires collected at baseline, at 24 weeks, and at the study termination visit.;Primary end point(s): Incidence rate (i.e., the mean number of acute serious bacterial infections per patientyear) of acute serious bacterial infections (bacterial pneumonia, bacteremia/sepsis, bacterial meningitis, visceral absce | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Serum IgG trough levels before each infusion of KIg10 and at the study termination visit (week 51/52). 2. IgG subclasses levels (IgG1, IgG2, IgG3, IgG4) before infusions 1, 5, 9 and 13 for the 28-day infusion schedule, and before infusions 1, 7, 11 and 17 for the 21-day infusion schedule. 3. Frequency of patients with total IgG below 6 g/L criteria. 4. Anti-tetanus toxoid antibody level (quantitative assay) before infusions 1, 5, 9 and 13 for the 28-day infusion schedule and before infusions 1, 7, 11 and 17 for the 21-day infusion schedule. 5. Anti-pneumococcal capsular polysaccharide antibody level (quantitative assay) before infusions 1, 5, 9 and 13 for the 28-day infusion schedule and before infusions 1, 7, 11 and 17 for the 21-day infusion schedule. 6. Anti-measles antibody level (quantitative assay) before infusions 1, 5, 9 and 13 for the 28-day infusion schedule and before infusions 1, 7, 11 and 17 for the 21-day infusion schedule. 7. Anti-Haemophilus influenza type b antibody level (quantitative assay) before infusions 1, 5, 9 and 13 for the 28-day infusion schedule and before infusions 1, 7, 11 and 17 for the 21-day infusion schedule. 8. Incidence rate (i.e., the mean number per patient-year) of any infection other than acute serious bacterial infections from day 1 to week 51/52. 9. Duration of any infection other than acute serious bacterial infections from day 1 to week 51/52. 10.Incidence rate (i.e. the mean number per patient-year) of fever episodes, from day 1 to week 51/52. 11.Duration of fever episodes, from day 1 to week 51/52. 12.Overall hospitalization days from day 1 to week 51/52. 13.Days of hospitalizations due to infection from day 1 to week 51/52. 14.Incidence rate (i.e. the mean number per patient-year) of patient on antibiotics for the treatment of any kind of infection from day 1 to week 51/52. 15.Duration of patients on antibiotics for the treatment of any kind of infection from day 1 to week 51/52 | — |
Countries
Hungary, Italy, Portugal, Russian Federation, Slovakia
Contacts
Public ContactClinical Research Department
Cromsource S.r.l
Outcome results
None listed