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Clinical Assessment of Pharmacokinetics, Efficacy, and Safety of 10% IVIg in Pediatric PID Patients (KIDCARES10) (KIDCARES10)

Primary Purpose

Primary Immunodeficiency Disease

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Kedrion IVIG 10%
Sponsored by
Kedrion S.p.A.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Immunodeficiency Disease focused on measuring Immunoglobulin, Kedrion IVIG 10%, IgG Antibodies, Agammaglobulinemia, Hypogammaglobulinemia, Pediatric

Eligibility Criteria

2 Years - 16 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Written informed consent/assent obtained from the patient and his/her parent(s) or legally 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 et 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 (< 18) at the time of study termination visit.
  4. Received 200 to 800 mg/kg of a commercially available IVIg therapy in the range of 21- or 28-day intervals (±3 or ±4 days, respectively) for at least 3 infusion cycles prior to screening. (NOTE: Other IVIgs will be prohibited after ICF signature and until study end, week 51/52).
  5. At least 2 documented IgG trough levels while receiving an IVIg, of ≥ 6 g/L obtained at 2 infusion cycles within 12 months (1 must be within 6 months) prior to ICF signature.
  6. Patient and his/her parent(s)/legal guardian(s) are willing to comply with all requirements of the protocol.
  7. Females of child-bearing potential with a negative pregnancy test (serum or urine) and who agree to employ adequate birth control measures during the study, such as:

    1. sexual abstinence, to be evaluated in relation to the preferred and usual lifestyle of the subject;
    2. male or female condom with or without spermicide;
    3. cap, diaphragm or sponge with spermicide;
    4. progestogen-only oral hormonal contraception, if already used in the past on medical prescription.

    Adequate birth control measures should be maintained throughout the study under parental control.

  8. Authorization to access personal health information.
  9. Patients previously participating in a clinical trial with another experimental IVIg may be enrolled if they have received stable commercially available IVIg therapy for at least 3 infusion cycles (21 or 28 days) prior to screening.
  10. Patients currently on treatment with any subcutaneous immunoglobulin (SCIG) can be enrolled if they are switched to stable commercially available IVIg therapy for at least 3 infusion cycles (21 or 28 days) prior to screening.
  11. Males or females with a body weight greater than or equal to 15 kg (≥15 kg).

Exclusion Criteria:

  1. Newly diagnosed PID and naïve to IgG replacement therapy.
  2. 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+ <300 cell/mm3] and an absent or particularly low proliferative response [10% of the lower normal range] to phytohaemagglutinin P [PHA]).
  3. History of severe or serious reactions or hypersensitivity to IVIg or other injectable forms of IgG.
  4. History of thrombotic events including deep vein thrombosis, cerebrovascular accident, pulmonary embolism, transient ischemic attacks, or myocardial infarction, as defined by at least 1 event in patient's lifetime.
  5. IgA deficiency with documented antibodies to IgA.
  6. Received blood products that have not undergone viral inactivation measures within 12 months prior to ICF signature.
  7. Significant protein losing enteropathy, nephrotic syndrome, or lymphangiectasia.
  8. An acute infection as documented by culture or diagnostic imaging and/or a body temperature ≥38.5° C (≥101.3° F) within 7 days prior to screening.
  9. Acquired immunodeficiency syndrome (AIDS) and/or hepatitis B/C active disease at ICF signature.
  10. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 times of the upper limit of normal for the laboratory designated for the study.
  11. Using an implanted venous access device.
  12. Profound anemia, defined according to the patient's age as shown in the following table (Dallman PR, 1979) or persistent severe neutropenia (≤ 500 neutrophils per mm3) or persistent lymphopenia of less than 500 cells per microliter.

    Age (years) | Hemoglobin (g/dl) 2-6 < 11.5 6-12 < 11.5 12-18 (female) < 12.0 12-18 (male) < 13.0

  13. A severe chronic condition such as renal failure [defined as abnormalities in kidney structure or function that are present for more than 3 months and have health implications. The disease is classified on the basis of cause and category of glomerular filtration rate (GFR) (G1 to G5) and albuminuria (A1 to A3) (KIDIGO, 2017). See the following table], 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.

    GFR* categories | Range | Persistent Albuminuria categories | Range (ml/min/1.73 m2) G1 ≥ 90 A1 < 30 mg/g / < 3 mg/mmol G2 60- 89 A2 30-300 mg/g/ 3-30 mg/mmol G3a 45-59 A3 >300 mg/g / > 30 mg/mmol G3b 30-44 G4 15-29 G5 < 15

    *GFR calculated according to Bedside Schwartz equation

  14. 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.
  15. 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.
  16. Patient must not be receiving the following medication from at least 30 days prior to ICF signature:

    1. Steroids, oral or parenteral, at a daily dose of ≥ 0.15 mg/kg/day of prednisone or equivalent).
    2. Other immunosuppressive drugs (including monoclonal antibodies) or chemotherapy.
  17. 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.
  18. Participated in another clinical study within 30 days prior to ICF signature.
  19. Active drug or alcohol abuse or history of drug or alcohol abuse within the 6 months before screening
  20. Direct relative of an employee of the CRO, the study site, or Kedrion.
  21. Previously treated under this protocol.
  22. Unable to provide informed consent.
  23. 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.
  24. Patients with Hypersensitivity to the active substance or to any of the excipients.

Sites / Locations

  • Dél-Pesti Centrumkórház - Országos Hematológiai És Infektológiai IntézetRecruiting
  • SST Spedali Civili di BresciaRecruiting
  • Azienda Ospedaliero-Universitaria - Ospedale Pediatrico Meyer
  • I.R.C.C.S. Istituto Giannina Gaslini
  • Fondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicRecruiting
  • Azienda Ospedaliera Universitaria "Federico II"Recruiting
  • Fondazione Policlinico Tor Vergata
  • IRCCS Ospedale Pediatrico Bambino GesùRecruiting
  • Centro Hospitalar Lisboa Central - Hospital Dona Estefânia
  • Centro Hospitalar Universitário do Porto - Hospital Santo AntónioRecruiting
  • Children's City Clinical Hospital No. 9 named after G.N. Speransky, Moscow City Health DepartmentRecruiting
  • Dmitry Rogachev National Medical Research Center for Pediatric Hematology, Oncology and ImmunologyRecruiting
  • Národný ústav detských chorôb (National Institute of Pediatric Diseases)Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental: Kedrion IVIG 10%

Arm Description

Participants will receive intravenous infusion of Kedrion IVIG 10% at a dose of 200 to 800 milligram per kilogram (mg/kg) body weight every 21 or 28 days for period of 48 weeks.

Outcomes

Primary Outcome Measures

Incidence Rate of Acute Serious Bacterial Infections
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 abscess, osteomyelitis/septic arthritis) according to pre-specified criteria).

Secondary Outcome Measures

Serum Immunoglobulin G (IgG) trough levels
Immunoglobulin G (IgG) subclasses levels (IgG1, IgG2, IgG3, IgG4)
Frequency of patients with total Immunoglobulin G (IgG) below 6 g/L
Anti-tetanus toxoid antibody level
The quantitative evaluation will be reported
Anti-pneumococcal capsular polysaccharide antibody level
The quantitative evaluation will be reported
Anti-measles antibody level
The quantitative evaluation will be reported
Anti-Haemophilus influenza type b antibody level
The quantitative evaluation will be reported
Incidence rate (i.e., the mean number per patient-year) of any infection other than acute serious bacterial infections
Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion.
Duration of any infection other than acute serious bacterial infections
Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion.
Incidence rate (i.e. the mean number per patient-year) of fever episodes
Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion.
Duration of fever episodes
Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion.
Overall hospitalization days
Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion.
Days of hospitalizations due to infection
Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion.
Incidence rate (i.e. the mean number per patient-year) of patient on antibiotics for the treatment of any kind of infection
Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion.
Duration of patients on antibiotics for the treatment of any kind of infection
Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion.
Days of missed work/school/other major activities due to infections
Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion.
Pediatric Quality of Life Inventory (Pedsql) Score
The PedsQL™ Measurement Model is a modular approach to measuring health-related QoL in healthy children and adolescents and those with acute and chronic health conditions. The 23-item PedsQL™ Generic Core Scales were designed to measure the core dimension of health as delineated by the World Health Organization, as well as role (school) functioning. The total scale score (23 items) consists of Physical health summary score (8 items) and Psychosocial health summary score (15 items). Physical health summary includes Physical Functioning (8 items) and Psychosocial health summary score includes Emotional Functioning (5 items), Social Functioning (5 items) and School Functioning (5 items). The overall range for PedsQL scores is 0 to 100, with a higher score indicating better quality of life.
Number of Adverse Events (%) and proportion of patients experiencing at least one Adverse Event (AE)
Number of Serisous AEs (%) and proportion of patients experiencing at least one Serious Adverse Event (SAE)
Number of related infusion AEs (%) and proportion of patients experiencing at least 1 of such related infusion AE.
The proportion and number of KIg10 infusions for which the infusion rate is decreased due to Adverse Events.
Number and proportion of infusions with one or more infusion (temporally-associated) Adverse Event.
Number of Participants With Clinically Significant Change from Baseline Values in Vital Signs, Physical Examinations, Safety Laboratory Tests(hematology, serum chemistry and urinalysis).
Number of participants with clinically significant change from baseline in vital signs (including blood pressure, heart rate and temperature); Physical examination (including evaluation of all body systems, body weight, height and Tanner Staging); Safety Laboratory Tests (including hematology, serum chemistry, and urinalysis) will be reported.
The proportion and number of patients with a positive Coomb's test
The proportion and number of patients with a positive urine hemosiderin test
Serum haptoglobin level
Serum Total Immunoglobulin G (IgG) levels, IgG Subclasses Levels, and Selected Specific Antibody Levels
Plasma Concentration - Time Curve Of Total Immunoglobulin G (IgG)
Elimination Half-Life (t1/2) of Total Immunoglobulin G (IgG)
Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC(0-T)) of Total Immunoglobulin G (IgG)
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC[0-inf]) of Total Immunoglobulin G (IgG)
Volume of Distribution of Total Immunoglobulin G (IgG)
Maximum Observed Plasma Concentration (Cmax) Of Total IgG
Time to Reach the Maximum Plasma Concentration (Tmax) of Total Immunoglobulin G (IgG)
Elimination Rate Constant of Total Immunoglobulin G (IgG)
Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-Tau) of Total Immunoglobulin G (IgG)
Plasma Concentration-Time Curve Of Specific Immunoglobulin G (IgG) Antibodies
The quantitative evaluation of the anti-Tetanus toxoid, anti-pneumococcal capsular polysaccharide, anti-Haemophilus influenza type B and anti-measles antibodies level will be reported
Elimination Half-Life (t1/2) of Specific IgG Antibodies
Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC(0-T)) of Specific Immunoglobulin G (IgG) Antibodies
Volume Of Distribution of Specific Immunoglobulin G (IgG) Antibodies
Maximum Observed Plasma Concentration (Cmax) of Specific Immunoglobulin G (IgG) Antibodies
Time to Reach the Maximum Plasma Concentration (Tmax) of Specific Immunoglobulin G (IgG) Antibodies
Elimination Rate Constant of Specific Immunoglobulin G (IgG) Antibodies
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Specific Immunoglobulin G (IgG) Antibodies
Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-Tau) of Specific Immunoglobulin G (IgG) Antibodies

Full Information

First Posted
June 11, 2021
Last Updated
June 21, 2023
Sponsor
Kedrion S.p.A.
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1. Study Identification

Unique Protocol Identification Number
NCT04944979
Brief Title
Clinical Assessment of Pharmacokinetics, Efficacy, and Safety of 10% IVIg in Pediatric PID Patients (KIDCARES10)
Acronym
KIDCARES10
Official Title
A Phase III, Open-label, Prospective, Multicenter Study to Assess Efficacy, Safety, and Pharmacokinetics of Kedrion Intravenous Human Normal Immunoglobulin (IVIg) 10% in Pediatric Patients Affected by Primary Immunodeficiency Disease (PID)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 31, 2021 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kedrion S.p.A.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to assess efficacy, safety and pharmacokinetics of Kedrion Immunoglobulin 10% (KIg10) in pediatric patients with Primary Immunodeficiency Disease (PID).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Immunodeficiency Disease
Keywords
Immunoglobulin, Kedrion IVIG 10%, IgG Antibodies, Agammaglobulinemia, Hypogammaglobulinemia, Pediatric

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental: Kedrion IVIG 10%
Arm Type
Experimental
Arm Description
Participants will receive intravenous infusion of Kedrion IVIG 10% at a dose of 200 to 800 milligram per kilogram (mg/kg) body weight every 21 or 28 days for period of 48 weeks.
Intervention Type
Biological
Intervention Name(s)
Kedrion IVIG 10%
Intervention Description
Kedrion intravenous immunoglobulin (IVIg) 10%
Primary Outcome Measure Information:
Title
Incidence Rate of Acute Serious Bacterial Infections
Description
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 abscess, osteomyelitis/septic arthritis) according to pre-specified criteria).
Time Frame
From Baseline (Day 1) up to week 51/52
Secondary Outcome Measure Information:
Title
Serum Immunoglobulin G (IgG) trough levels
Time Frame
Before each infusion and at the study termination visit (Week 51/52)
Title
Immunoglobulin G (IgG) subclasses levels (IgG1, IgG2, IgG3, IgG4)
Time Frame
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
Title
Frequency of patients with total Immunoglobulin G (IgG) below 6 g/L
Time Frame
Day 1 up to week 51/52
Title
Anti-tetanus toxoid antibody level
Description
The quantitative evaluation will be reported
Time Frame
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
Title
Anti-pneumococcal capsular polysaccharide antibody level
Description
The quantitative evaluation will be reported
Time Frame
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
Title
Anti-measles antibody level
Description
The quantitative evaluation will be reported
Time Frame
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
Title
Anti-Haemophilus influenza type b antibody level
Description
The quantitative evaluation will be reported
Time Frame
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
Title
Incidence rate (i.e., the mean number per patient-year) of any infection other than acute serious bacterial infections
Description
Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion.
Time Frame
From day 1 to week 51/52
Title
Duration of any infection other than acute serious bacterial infections
Description
Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion.
Time Frame
From day 1 to week 51/52
Title
Incidence rate (i.e. the mean number per patient-year) of fever episodes
Description
Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion.
Time Frame
From day 1 to week 51/52
Title
Duration of fever episodes
Description
Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion.
Time Frame
From day 1 to week 51/52
Title
Overall hospitalization days
Description
Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion.
Time Frame
From day 1 to week 51/52
Title
Days of hospitalizations due to infection
Description
Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion.
Time Frame
From day 1 to week 51/52
Title
Incidence rate (i.e. the mean number per patient-year) of patient on antibiotics for the treatment of any kind of infection
Description
Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion.
Time Frame
From day 1 to week 51/52
Title
Duration of patients on antibiotics for the treatment of any kind of infection
Description
Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion.
Time Frame
From day 1 to week 51/52
Title
Days of missed work/school/other major activities due to infections
Description
Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion.
Time Frame
From day 1 to week 51/52
Title
Pediatric Quality of Life Inventory (Pedsql) Score
Description
The PedsQL™ Measurement Model is a modular approach to measuring health-related QoL in healthy children and adolescents and those with acute and chronic health conditions. The 23-item PedsQL™ Generic Core Scales were designed to measure the core dimension of health as delineated by the World Health Organization, as well as role (school) functioning. The total scale score (23 items) consists of Physical health summary score (8 items) and Psychosocial health summary score (15 items). Physical health summary includes Physical Functioning (8 items) and Psychosocial health summary score includes Emotional Functioning (5 items), Social Functioning (5 items) and School Functioning (5 items). The overall range for PedsQL scores is 0 to 100, with a higher score indicating better quality of life.
Time Frame
At baseline, week 24, and study termination visit
Title
Number of Adverse Events (%) and proportion of patients experiencing at least one Adverse Event (AE)
Time Frame
From Baseline (Day 1) up to Week 51/52
Title
Number of Serisous AEs (%) and proportion of patients experiencing at least one Serious Adverse Event (SAE)
Time Frame
From Baseline (Day 1) up to Week 51/52
Title
Number of related infusion AEs (%) and proportion of patients experiencing at least 1 of such related infusion AE.
Time Frame
From Baseline (Day 1) up to Week 51/52
Title
The proportion and number of KIg10 infusions for which the infusion rate is decreased due to Adverse Events.
Time Frame
From Baseline (Day 1) up to Week 51/52
Title
Number and proportion of infusions with one or more infusion (temporally-associated) Adverse Event.
Time Frame
From Baseline (Day 1) up to Week 51/52
Title
Number of Participants With Clinically Significant Change from Baseline Values in Vital Signs, Physical Examinations, Safety Laboratory Tests(hematology, serum chemistry and urinalysis).
Description
Number of participants with clinically significant change from baseline in vital signs (including blood pressure, heart rate and temperature); Physical examination (including evaluation of all body systems, body weight, height and Tanner Staging); Safety Laboratory Tests (including hematology, serum chemistry, and urinalysis) will be reported.
Time Frame
Up to Week 51/52
Title
The proportion and number of patients with a positive Coomb's test
Time Frame
At infusion 7 for the 28-day infusion schedule and infusion 9 for the 21-day infusion schedule
Title
The proportion and number of patients with a positive urine hemosiderin test
Time Frame
At infusion 7 for the 28-day infusion schedule and infusion 9 for the 21- day infusion schedule
Title
Serum haptoglobin level
Time Frame
At infusion 7 for the 28-day infusion schedule and infusion 9 for the 21-day infusion schedule.
Title
Serum Total Immunoglobulin G (IgG) levels, IgG Subclasses Levels, and Selected Specific Antibody Levels
Time Frame
Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule)
Title
Plasma Concentration - Time Curve Of Total Immunoglobulin G (IgG)
Time Frame
Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule)
Title
Elimination Half-Life (t1/2) of Total Immunoglobulin G (IgG)
Time Frame
Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule)
Title
Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC(0-T)) of Total Immunoglobulin G (IgG)
Time Frame
Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule)
Title
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC[0-inf]) of Total Immunoglobulin G (IgG)
Time Frame
Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule)
Title
Volume of Distribution of Total Immunoglobulin G (IgG)
Time Frame
Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule)
Title
Maximum Observed Plasma Concentration (Cmax) Of Total IgG
Time Frame
Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule)
Title
Time to Reach the Maximum Plasma Concentration (Tmax) of Total Immunoglobulin G (IgG)
Time Frame
Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule)
Title
Elimination Rate Constant of Total Immunoglobulin G (IgG)
Time Frame
Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule)
Title
Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-Tau) of Total Immunoglobulin G (IgG)
Time Frame
Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule)
Title
Plasma Concentration-Time Curve Of Specific Immunoglobulin G (IgG) Antibodies
Description
The quantitative evaluation of the anti-Tetanus toxoid, anti-pneumococcal capsular polysaccharide, anti-Haemophilus influenza type B and anti-measles antibodies level will be reported
Time Frame
Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule)
Title
Elimination Half-Life (t1/2) of Specific IgG Antibodies
Time Frame
Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule)
Title
Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC(0-T)) of Specific Immunoglobulin G (IgG) Antibodies
Time Frame
Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule)
Title
Volume Of Distribution of Specific Immunoglobulin G (IgG) Antibodies
Time Frame
Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule)
Title
Maximum Observed Plasma Concentration (Cmax) of Specific Immunoglobulin G (IgG) Antibodies
Time Frame
Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule)
Title
Time to Reach the Maximum Plasma Concentration (Tmax) of Specific Immunoglobulin G (IgG) Antibodies
Time Frame
Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule)
Title
Elimination Rate Constant of Specific Immunoglobulin G (IgG) Antibodies
Time Frame
Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule)
Title
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Specific Immunoglobulin G (IgG) Antibodies
Time Frame
Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule)
Title
Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-Tau) of Specific Immunoglobulin G (IgG) Antibodies
Time Frame
Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent/assent obtained from the patient and his/her parent(s) or legally acceptable representative indicating that they understand the purpose of and procedures required for the study and are willing to participate in it. 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 et 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). 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 (< 18) at the time of study termination visit. Received 200 to 800 mg/kg of a commercially available IVIg therapy in the range of 21- or 28-day intervals (±3 or ±4 days, respectively) for at least 3 infusion cycles prior to screening. (NOTE: Other IVIgs will be prohibited after ICF signature and until study end, week 51/52). At least 2 documented IgG trough levels while receiving an IVIg, of ≥ 6 g/L obtained at 2 infusion cycles within 12 months (1 must be within 6 months) prior to ICF signature. Patient and his/her parent(s)/legal guardian(s) are willing to comply with all requirements of the protocol. Females of child-bearing potential with a negative pregnancy test (serum or urine) and who agree to employ adequate birth control measures during the study, such as: sexual abstinence, to be evaluated in relation to the preferred and usual lifestyle of the subject; male or female condom with or without spermicide; cap, diaphragm or sponge with spermicide; progestogen-only oral hormonal contraception, if already used in the past on medical prescription. Adequate birth control measures should be maintained throughout the study under parental control. Authorization to access personal health information. Patients previously participating in a clinical trial with another experimental IVIg may be enrolled if they have received stable commercially available IVIg therapy for at least 3 infusion cycles (21 or 28 days) prior to screening. Patients currently on treatment with any subcutaneous immunoglobulin (SCIG) can be enrolled if they are switched to stable commercially available IVIg therapy for at least 3 infusion cycles (21 or 28 days) prior to screening. Males or females with a body weight greater than or equal to 15 kg (≥15 kg). 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+ <300 cell/mm3] and an absent or particularly low proliferative response [10% of the lower normal range] to phytohaemagglutinin P [PHA]). History of severe or serious reactions or hypersensitivity to IVIg or other injectable forms of IgG. History of thrombotic events including deep vein thrombosis, cerebrovascular accident, pulmonary embolism, transient ischemic attacks, or myocardial infarction, as defined by at least 1 event in patient's lifetime. IgA deficiency with documented antibodies to IgA. Received blood products that have not undergone viral inactivation measures within 12 months prior to ICF signature. Significant protein losing enteropathy, nephrotic syndrome, or lymphangiectasia. An acute infection as documented by culture or diagnostic imaging and/or a body temperature ≥38.5° C (≥101.3° F) within 7 days prior to screening. Acquired immunodeficiency syndrome (AIDS) and/or hepatitis B/C active disease at ICF signature. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 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 the following table (Dallman PR, 1979) or persistent severe neutropenia (≤ 500 neutrophils per mm3) or persistent lymphopenia of less than 500 cells per microliter. Age (years) | Hemoglobin (g/dl) 2-6 < 11.5 6-12 < 11.5 12-18 (female) < 12.0 12-18 (male) < 13.0 A severe chronic condition such as renal failure [defined as abnormalities in kidney structure or function that are present for more than 3 months and have health implications. The disease is classified on the basis of cause and category of glomerular filtration rate (GFR) (G1 to G5) and albuminuria (A1 to A3) (KIDIGO, 2017). See the following table], 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. GFR* categories | Range | Persistent Albuminuria categories | Range (ml/min/1.73 m2) G1 ≥ 90 A1 < 30 mg/g / < 3 mg/mmol G2 60- 89 A2 30-300 mg/g/ 3-30 mg/mmol G3a 45-59 A3 >300 mg/g / > 30 mg/mmol G3b 30-44 G4 15-29 G5 < 15 *GFR calculated according to Bedside Schwartz equation 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 active substance or to any of the excipients.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nicola Rovai
Phone
+39 335 6524750
Email
n.rovai@kedrion.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chiara Azzari
Organizational Affiliation
Azienda Ospedaliero-Universitaria Ospedale Pediatrico Meyer - Italy
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dél-Pesti Centrumkórház - Országos Hematológiai És Infektológiai Intézet
City
Budapest
Country
Hungary
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gergely Kriván
First Name & Middle Initial & Last Name & Degree
Gergely Kriván
Facility Name
SST Spedali Civili di Brescia
City
Brescia
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Raffaele Badolato
First Name & Middle Initial & Last Name & Degree
Raffaele Badolato
First Name & Middle Initial & Last Name & Degree
Vassilios Lougaris
Facility Name
Azienda Ospedaliero-Universitaria - Ospedale Pediatrico Meyer
City
Firenze
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
I.R.C.C.S. Istituto Giannina Gaslini
City
Genova
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinic
City
Milano
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lucia Baselli
First Name & Middle Initial & Last Name & Degree
Lucia Baselli
Facility Name
Azienda Ospedaliera Universitaria "Federico II"
City
Napoli
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Claudio Pignata
First Name & Middle Initial & Last Name & Degree
Claudio Pignata
First Name & Middle Initial & Last Name & Degree
Emilia Cirillo
Facility Name
Fondazione Policlinico Tor Vergata
City
Roma
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Viviana Moschese
First Name & Middle Initial & Last Name & Degree
Viviana Moschese
Facility Name
IRCCS Ospedale Pediatrico Bambino Gesù
City
Roma
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caterina Cancrini
First Name & Middle Initial & Last Name & Degree
Caterina Cancrini
Facility Name
Centro Hospitalar Lisboa Central - Hospital Dona Estefânia
City
Lisbon
Country
Portugal
Individual Site Status
Active, not recruiting
Facility Name
Centro Hospitalar Universitário do Porto - Hospital Santo António
City
Porto
Country
Portugal
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laura Marques
Facility Name
Children's City Clinical Hospital No. 9 named after G.N. Speransky, Moscow City Health Department
City
Moscow
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexey Krapivkin
Facility Name
Dmitry Rogachev National Medical Research Center for Pediatric Hematology, Oncology and Immunology
City
Moscow
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna Shcherbina
Facility Name
Národný ústav detských chorôb (National Institute of Pediatric Diseases)
City
Bratislava
Country
Slovakia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Čižnár
First Name & Middle Initial & Last Name & Degree
Peter Čižnár

12. IPD Sharing Statement

Learn more about this trial

Clinical Assessment of Pharmacokinetics, Efficacy, and Safety of 10% IVIg in Pediatric PID Patients (KIDCARES10)

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