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出境医 / 临床实验 / Clinical Assessment of phaRmacokinetics, Efficacy, and Safety of 10% IVIg in PID Patients (CARES10)
Clinical Assessment of phaRmacokinetics, Efficacy, and Safety of 10% IVIg in PID Patients (CARES10)
Study Description
Brief Summary:
The purpose of this study is to assess efficacy and safety of Kedrion Immunoglobulin 10% (KIg10) in participants with Primary Immunodeficiency (PID).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Primary Immunodeficiency Disease | Biological: Kedrion IVIG 10% | Phase 3 |
Study Design
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 47 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase III, Open-label, Prospective, Multicenter Study to Assess Efficacy, Safety and Pharmacokinetics of Kedrion Intravenous Immunoglobulin (IVIg) 10% in Primary Immunodeficiency Disease (PID) Patients |
| Actual Study Start Date : | April 30, 2019 |
| Actual Primary Completion Date : | December 21, 2020 |
| Actual Study Completion Date : | December 21, 2020 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Kedrion IVIG 10%
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.
|
Biological: Kedrion IVIG 10%
Kedrion intravenous immunoglobulin (IVIg) 10%
|
Outcome Measures
Primary Outcome Measures :
- Incidence Rate of Acute Serious Bacterial Infections [ Time Frame: Day 1 up to Week 52 ]Incidence rate is defined as the mean number of acute serious bacterial infections (bacterial pneumonia, bacteraemia/sepsis, bacterial meningitis, visceral abscess, osteomyelitis/septic arthritis) per patient-year.
Secondary Outcome Measures :
- Serum Immunoglobulin G (IgG) Trough Levels [ Time Frame: Before each infusion and at the study termination visit (Week 51/52) ]
- Immunoglobulin G (IgG) Subclasses Levels (IgG1, IgG2, IgG3, IgG4) [ Time Frame: Before infusions on Day 1, 5, 9 and 13 (28-day infusion schedule) and before infusions on Day 1, 7, 11 and 17 (21-day infusion schedule) ]
- Number of Participants with Total Immunoglobulin G (IgG) Below 6 Gram Per Liter (g/L) Criteria [ Time Frame: Up to 12 months ]
- Anti-Tetanus Toxoid Antibody Level [ Time Frame: Before infusions on Day 1, 5, 9 and 13 (28-day infusion schedule) and before infusions on Day 1, 7, 11 and 17 (21-day infusion schedule) ]The quantitative evaluation of the anti-Tetanus toxoid antibody level will be reported.
- Anti-Pneumococcal Capsular Polysaccharide Antibody Level [ Time Frame: Before infusions on Day 1, 5, 9 and 13 (28-day infusion schedule) and before infusions on Day 1, 7, 11 and 17 (21-day infusion schedule) ]The quantitative evaluation of the Anti-Pneumococcal Capsular Polysaccharide Antibody level will be reported.
- Anti-Measles Antibody Level [ Time Frame: Before infusions on Day 1, 5, 9 and 13 (28-day infusion schedule) and before infusions on Day 1, 7, 11 and 17 (21-day infusion schedule) ]The quantitative evaluation of the Anti-Measles Antibody level will be reported
- Anti-Haemophilus Influenza Type B Antibody Level [ Time Frame: Before infusions on Day 1, 5, 9 and 13 (28-day infusion schedule) and before infusions on Day 1, 7, 11 and 17 (21-day infusion schedule) ]The quantitative evaluation of the Anti-Haemophilus Influenza Type B Antibody Level will be reported.
- Incidence Rate of Any Infection Other Than Acute Serious Bacterial Infections [ Time Frame: Day 1 up to week 51 and 52 ]Information regarding incidence rate of infections other than serious acute bacterial infections collected by the participant/participants parent(s)/legal guardian(s) in the Participant Diary or during clinic visit will be recorded.
- Duration Of Any Infection Other Than Acute Serious Bacterial Infections [ Time Frame: Day 1 up to Week 51 and 52 ]Information regarding infections (other than serious acute bacterial infections), including the number of days for resolution, collected by the participant/participant's parent(s)/legal guardian(s) in the Participant Diary or during clinic visit will be recorded.
- Incidence Rate of Fever Episodes [ Time Frame: Day 1 up to Week 51 and 52 ]Information regarding fever episodes collected by the participant/participant's parent(s)/legal guardian(s) in the Participant Diary or during clinic visit will be recorded.
- Duration Of Fever Episodes [ Time Frame: Day 1 up to Week 51 and 52 ]Information regarding duration of Fever Episodes will be collected by the participant/participant's parent(s)/legal guardian(s) in the Participant Diary or during clinic visit will be recorded.
- Overall Hospitalization Days [ Time Frame: Day 1 up to week 51 and 52 ]The participant/participant's parent(s)/legal guardian(s) will also provide the information regarding the overall hospitalization days due to infection in the Patient Diary that will be provided starting from the first infusion
- Days of Hospitalizations Due To Infection [ Time Frame: Day 1 up to Week 51 and 52 ]The participant/participant's parent(s)/legal guardian(s) will also provide the information regarding days of hospitalizations due to infection in the Patient Diary that will be provided starting from the first infusion
- Incidence Rate of Participants on Antibiotics for Treatment of Any Kind of Infections [ Time Frame: Day 1 up to Week 51 and 52 ]The information regarding the use of therapeutic antibiotics for the treatment of any kind of infections in the Participant Diary will be reported starting from the first infusion visit.
- Duration of Participants on Antibiotics for Treatment Of Any Kind of Infection [ Time Frame: Day 1 up to Week 51 and 52 ]The information regarding the duration of participant on antibiotics for the treatment of any kind of infections in the Participant Diary that will be reported starting from the first infusion visit.
- Days of Missed Work/School/Other Major Activities Due to Infections [ Time Frame: Day 1 up to Week 51 and 52 ]
- Pediatric Quality of Life Inventory (Pedsql) Score [ Time Frame: At Baseline, Week 24 and Week 52 ]
PedsQL™ Measurement Model is a modular approach to measure health-related Quality of Life Questionnaires (QoL) in healthy children,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 Participants Experiencing at Least one Adverse events (AEs) [ Time Frame: Baseline (Day 1) up to Week 52 ]
- Number of Participants Experiencing at Least one Serious Adverse Events (SAEs) [ Time Frame: Baseline (Day 1) up to Week 52 ]
- Number of Participants Experiencing at Least one Related Infusion Adverse events (AEs) [ Time Frame: Baseline (Day 1) up to Week 52 ]
- Number of Infusions With Decreased Infusion Rate Due to Adverse Events (AEs) [ Time Frame: Baseline (Day 1) up to Week 52 ]
- Number of Infusions With one or More Infusion Associated Adverse Events (AEs) [ Time Frame: Baseline (Day 1) up to Week 52 ]
- Number of Participants With Clinically Significant Change from Baseline Values in Vital Signs, Physical Examinations, Safety Laboratory Tests [ Time Frame: Up to Week 52 ]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 and body weight); Safety Laboratory Tests (including hematology, serum chemistry, and urinalysis) will be reported.
- Number of Participants With Positive Coomb's Test [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- Number of Participants With Positive Urine Hemosiderin Test [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- Number of Participants With Plasma-free Haemoglobin Level [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- Number of Participants With Serum Haptoglobin Level [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- Serum Total Immunoglobulin G (IgG) IgG levels, IgG Subclasses Levels and Selected Specific Antibody Levels [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- Plasma Concentration- Time Curve Of Total Immunoglobulin G (IgG) [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- Elimination Half-Life (t1/2) of Total Immunoglobulin G (IgG) [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- 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: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC[0-inf]) of Total Immunoglobulin G (IgG) [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- Volume of Distribution of Total Immunoglobulin G (IgG) [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- Maximum Observed Plasma Concentration (Cmax) Of Total IgG [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- Time to Reach the Maximum Plasma Concentration (Tmax) of Total Immunoglobulin G (IgG) [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- Elimination Rate Constant of Total Immunoglobulin G (IgG) [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-Tau) of Total Immunoglobulin G (IgG) [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- Plasma Concentration-Time Curve Of Specific Immunoglobulin G (IgG) Antibodies [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]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 [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- 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: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- Volume Of Distribution of Specific Immunoglobulin G (IgG) Antibodies [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- Maximum Observed Plasma Concentration (Cmax) of Specific Immunoglobulin G (IgG) Antibodies [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- Time to Reach the Maximum Plasma Concentration (Tmax) of Specific Immunoglobulin G (IgG) Antibodies [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- Elimination Rate Constant of Specific Immunoglobulin G (IgG) Antibodies [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Specific Immunoglobulin G (IgG) Antibodies [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-Tau) of Specific Immunoglobulin G (IgG) Antibodies [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- Average Concentration of Drug Over the Dosing Interval (Cave) [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
- Average Concentration of Drug at Steady State Clearance (CLss) [ Time Frame: At 5th Infusion (During 28 Day Infusion) and 7th Infusion (During 21 Day Infusion) ]
Eligibility Criteria
| Ages Eligible for Study: | 2 Years to 70 Years (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Written informed consent/assent obtained from patients/patients' 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, requiring treatment with IVIg and have 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 [that is at least 2 standard deviations under the mean level per age])
- Male or female, ages 2 to 70 years at screening
- Received 200 to 800 mg/kg of a commercially available IVIg therapy in the range of 21- or 28-day intervals (±3 days or ±4 days, respectively) for at least 3 infusion cycles prior to screening
- At least 2 documented IgG trough levels while receiving an IVIg, of greater than or equals to (>=) 6 gram per liter (g/L) obtained at 2 infusion cycles within 12 months (1 must be within 6 months) prior to Informed Consent Form (ICF) signature
- Participant is willing to comply all requirements of the protocol.
- Females of child-bearing potential with a negative urine pregnancy test and who agree to employ adequate birth control measures during the study
- Authorization to access personal health information
- Participant 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
- Participant 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
Exclusion Criteria:
- Newly diagnosed PID and 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 cells per cubic millimetre (cell/mm3)] and an absent or particularly low proliferative response [10% of the lower normal range] to phytohaemagglutinin P [PHA])
- Has history of severe or serious reactions or hypersensitivity to IVIg or other injectable forms of IgG
- Has 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 participant's lifetime
- Has IgA deficiency with documented antibodies to IgA
- Have received blood products that have not undergone viral inactivation measures within 12 months prior to Informed Consent Form (ICF) signature
- 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 >= 38 degree Celsius (°C) (>=100.4 degree Fahrenheit (°F) within 7 days prior to screening
- Has acquired immunodeficiency syndrome (AIDS) and/or hepatitis B/C active disease at ICF signature
- 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
- Using an implanted venous access device
- Has profound anemia (haemoglobin less than10 gram per decilitre (g/dl)) or persistent severe neutropenia (<= 1000 neutrophils per millimiter cube (mm^3) or lymphopenia of less than 500 cells per microliter
- Have 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, hyper viscosity, 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. Normal values for serum creatinine are the following: a) Female (18+ years): 45 - 84 micromole per liter (μmol/L) or 0.51 - 0.95 milligrams per decilitre (mg/dl); b) Male (18+ years): 59 - 103 μmol/L or 0.67 - 1.17 mg/dl
- Has 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
- Has history of pharmacoresistant epilepsy or multiple episodes of migraine (defined as at least 1 episode within 6 months of ICF signature) not completely controlled by medication
- Participants must not be receiving steroids (oral or parenteral daily dose of>= 0.15 milligram per kilogram per day (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 ICF signature
- Has history of drug or alcohol abuse within the 6 months before screening
- Has Employed or a direct relative of an employee of the CRO, the study site, or the Sponsor
- Previously treated under this protocol
- Unable to provide informed consent or provide informed consent by a legally authorized representative
Contacts and Locations
Locations
| United States, Florida | |
| Allergy Associates of the Palm Beaches | |
| North Palm Beach, Florida, United States, 33408 | |
| United States, Illinois | |
| Rush University Medical Center | |
| Chicago, Illinois, United States, 60612 | |
| United States, Kansas | |
| Dr. Henry J. Kanarek - Allergy, Asthma & Immunology | |
| Overland Park, Kansas, United States, 66211 | |
| United States, Minnesota | |
| Midwest Immunology Clinic and Infusion Center | |
| Plymouth, Minnesota, United States, 55446 | |
| United States, New Jersey | |
| Allergy and Immunology Associates | |
| Little Silver, New Jersey, United States, 07739 | |
| United States, New York | |
| University of Buffalo | |
| Buffalo, New York, United States, 14203 | |
| United States, Ohio | |
| Optimed Research | |
| Columbus, Ohio, United States, 43235 | |
| Ohio Clinical Research Associates, Inc. | |
| Mayfield Heights, Ohio, United States, 44124 | |
| Toledo Institute of Clinical Research Inc | |
| Toledo, Ohio, United States, 43617 | |
| United States, Texas | |
| Allergy Partners of North Texas Research | |
| Dallas, Texas, United States, 75230 | |
| AARA Research Center | |
| Dallas, Texas, United States, 75231 | |
Sponsors and Collaborators
Kedrion S.p.A.
Investigators
| Principal Investigator: | Medical Director | Kedrion SpA |
| Tracking Information | |||||
|---|---|---|---|---|---|
| First Submitted Date ICMJE | May 21, 2019 | ||||
| First Posted Date ICMJE | May 23, 2019 | ||||
| Last Update Posted Date | May 7, 2021 | ||||
| Actual Study Start Date ICMJE | April 30, 2019 | ||||
| Actual Primary Completion Date | December 21, 2020 (Final data collection date for primary outcome measure) | ||||
| Current Primary Outcome Measures ICMJE |
Incidence Rate of Acute Serious Bacterial Infections [ Time Frame: Day 1 up to Week 52 ] Incidence rate is defined as the mean number of acute serious bacterial infections (bacterial pneumonia, bacteraemia/sepsis, bacterial meningitis, visceral abscess, osteomyelitis/septic arthritis) per patient-year.
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| Original Primary Outcome Measures ICMJE | Same as current | ||||
| Change History | |||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE | Same as current | ||||
| Current Other Pre-specified Outcome Measures | Not Provided | ||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||
| Descriptive Information | |||||
| Brief Title ICMJE | Clinical Assessment of phaRmacokinetics, Efficacy, and Safety of 10% IVIg in PID Patients | ||||
| Official Title ICMJE | A Phase III, Open-label, Prospective, Multicenter Study to Assess Efficacy, Safety and Pharmacokinetics of Kedrion Intravenous Immunoglobulin (IVIg) 10% in Primary Immunodeficiency Disease (PID) Patients | ||||
| Brief Summary | The purpose of this study is to assess efficacy and safety of Kedrion Immunoglobulin 10% (KIg10) in participants with Primary Immunodeficiency (PID). | ||||
| Detailed Description | Not Provided | ||||
| Study Type ICMJE | Interventional | ||||
| Study Phase ICMJE | Phase 3 | ||||
| Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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| Condition ICMJE | Primary Immunodeficiency Disease | ||||
| Intervention ICMJE | Biological: Kedrion IVIG 10%
Kedrion intravenous immunoglobulin (IVIg) 10%
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| Study Arms ICMJE | Experimental: Kedrion IVIG 10%
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: Biological: Kedrion IVIG 10%
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| Publications * | Not Provided | ||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||
| Recruitment Status ICMJE | Completed | ||||
| Actual Enrollment ICMJE |
47 | ||||
| Original Estimated Enrollment ICMJE |
50 | ||||
| Actual Study Completion Date ICMJE | December 21, 2020 | ||||
| Actual Primary Completion Date | December 21, 2020 (Final data collection date for primary outcome measure) | ||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 2 Years to 70 Years (Child, Adult, Older Adult) | ||||
| Accepts Healthy Volunteers ICMJE | No | ||||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
| Listed Location Countries ICMJE | United States | ||||
| Removed Location Countries | Canada | ||||
| Administrative Information | |||||
| NCT Number ICMJE | NCT03961009 | ||||
| Other Study ID Numbers ICMJE | KIG10_US3_PID01 | ||||
| Has Data Monitoring Committee | Yes | ||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE | Not Provided | ||||
| Responsible Party | Kedrion S.p.A. | ||||
| Study Sponsor ICMJE | Kedrion S.p.A. | ||||
| Collaborators ICMJE | Not Provided | ||||
| Investigators ICMJE |
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| PRS Account | Kedrion S.p.A. | ||||
| Verification Date | May 2021 | ||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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