Clinical Assessment of Pharmacokinetics, Efficacy, and Safety of 10% IVIg in PID Patients

Kedrion S.p.A.47 enrolled

Overview

The purpose of this study was to assess efficacy and safety of Kedrion Immunoglobulin 10% (KIg10) in participants with Primary Immunodeficiency (PID).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Primary Immunodeficiency Disease

Interventions

Kedrion IVIG 10%BIOLOGICAL

Kedrion intravenous immunoglobulin (IVIg) 10%

Eligibility

Sex: ALLMin age: 2 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Written informed consent/assent obtained from participant/participant's 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 \[CD3+ \<300 cells per cubic millimeter (cell/mm3)\] 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 deciliter \[g/dl\]) or persistent severe neutropenia (\<= 1000 neutrophils per millimeter 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 (mcmol/L) or 0.51 - 0.95 milligrams per deciliter (mg/dl); b) Male (18+ years): 59 - 103 mcmol/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

Locations (11)

Allergy Associates of the Palm Beaches

North Palm Beach, Florida, United States

Rush University Medical Center

Chicago, Illinois, United States

Dr. Henry J. Kanarek - Allergy, Asthma & Immunology

Overland Park, Kansas, United States

Outcomes

Primary Outcomes

Incidence Rate of Acute Serious Bacterial Infections (ABSIs)

Incidence rate was defined as the mean number of acute serious bacterial infections (bacterial pneumonia, bacteremia/sepsis, bacterial meningitis, visceral abscess, osteomyelitis/septic arthritis) per participant-year according to pre-specified criteria.

Time frame: Baseline up to Week 51 (21-day dosing schedule) and Week 52 (28-day dosing schedule)

Secondary Outcomes

Serum Immunoglobulin G (IgG) Trough Levels

The serum IgG trough levels were collected and analyzed at a central laboratory.

Time frame: At baseline, Week 51 (21-day dosing schedule) and Week 52 (28-day dosing schedule)

Immunoglobulin G (IgG) Subclasses Levels (IgG1, IgG2, IgG3, IgG4)

IgG subclasses levels (IgG1, IgG2, IgG3, IgG4) were collected and analyzed at a central laboratory.

Time frame: At baseline, Weeks 16, 32 and 48 (28-day dosing schedule); Weeks 18, 30, 48 (21-day dosing schedule)

Number of Participants With Total Immunoglobulin G (IgG) Trough Levels Less Than or Equal to (<=) 6 Grams/Liter (g/L) Criteria

Number of participants with Total IgG trough levels \<= 6 g/L criteria were reported.

Time frame: Up to 12 months

Anti-Tetanus Toxoid Antibody Levels

The anti-tetanus toxoid antibody levels were collected and analyzed at a central laboratory. This antibody level was measured in international units per milliliter (IU/mL).

Time frame: Baseline, Weeks 16, 32 and 48 (28-day dosing schedule); Weeks 18, 30, 48 (21-day dosing schedule)

Anti-Pneumococcal Capsular Polysaccharide Antibody Levels

Anti-pneumococcal capsular polysaccharide antibody levels for serotype 1, serotype 12, serotype 14, serotype 17, serotype 19, serotype 2, serotype 20, serotype 22, serotype 23, serotype 26, serotype 3, serotype 4, serotype 34, serotype 43, serotype 5, serotype 51, serotype 54, serotype 56, serotype 57, serotype 68, serotype 70, serotype 8 and serotype 9 were collected and analyzed at a central laboratory.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Midwest Immunology Clinic and Infusion Center

Plymouth, Minnesota, United States

Allergy and Immunology Associates

Little Silver, New Jersey, United States

University of Buffalo

Buffalo, New York, United States

Optimed Research

Columbus, Ohio, United States

Ohio Clinical Research Associates, Inc.

Mayfield Heights, Ohio, United States

Toledo Institute of Clinical Research Inc

Toledo, Ohio, United States

Allergy Partners of North Texas Research

Dallas, Texas, United States

...and 1 more locations

Time frame: Baseline, Weeks 16, 32 and 48 (28-day dosing schedule); Weeks 18, 30, 48 (21-day dosing schedule)

Anti-Measles Antibody Levels

The anti-measles antibody levels were collected and analyzed at a central laboratory.

Time frame: Baseline, Weeks 16, 32 and 48 (28-day dosing schedule); Weeks 18, 30, 48 (21-day dosing schedule)

Anti-Haemophilus Influenza Type B Antibody Levels

The anti-haemophilus influenza type B antibody levels were collected and analyzed at central laboratory.

Time frame: Baseline, Weeks 16, 32 and 48 (28 -day dosing schedule); Weeks 18, 30, 48 (21-day dosing schedule)

Incidence Rate of Any Infection Other Than Acute Serious Bacterial Infections

Incidence rate was defined as the mean number of any infection other than acute serious bacterial infections (bacterial pneumonia, bacteraemia/sepsis, bacterial meningitis, visceral abscess, osteomyelitis/septic arthritis) per participant-year. Incidence rate of any infection other than acute bacterial serious infections collected by the participant/participants parent(s)/legal guardian(s) in the participant diary or during clinic visit was reported.

Time frame: Baseline up to Week 51 (21-day dosing schedule) and Week 52 (28-day dosing schedule)

Duration of Any Infection Other Than Acute Serious Bacterial Infections

Duration of any infection other than serious acute bacterial infections (in days) was calculated as date of stop of infection - date of start of infection + 1. Duration of any infection other than serious acute bacterial infections collected by the by the participant/participants parent(s)/legal guardian(s) in the participant diary or during clinic visit was reported.

Time frame: Baseline up to Week 51 (21-day dosing schedule) and Week 52 (28-day dosing schedule)

Incidence Rate of Fever Episodes

Incidence rate was defined as the mean number of fever episodes per participant-year. Incidence rate of fever episodes collected by the participant/participant's parent(s)/legal guardian(s) in the participant diary or during clinic visit were reported.

Time frame: Baseline up to Week 51 (21-day dosing schedule) and Week 52 (28-day dosing schedule)

Duration of Fever Episodes in Participants

Duration of fever episodes in participants was reported.

Time frame: Baseline up to Week 51 (21-day dosing schedule) and Week 52 (28-day dosing schedule)

Duration of Overall Participants Hospitalization

Duration of overall participants hospitalization was reported.

Time frame: Baseline up to Week 51 (21-day dosing schedule) and Week 52 (28-day dosing schedule)

Duration of Participants Hospitalization Due to Infection

Duration of participants hospitalization due to infection was reported.

Time frame: Baseline up to Week 51 (21-day dosing schedule) and Week 52 (28-day dosing schedule)

Incidence Rate of Antibiotics Episodes for Treatment of Any Kind of Infections

Incidence rate was defined as the mean number of antibiotics episodes per participant year. Incidence rate of participants on antibiotics for treatment of any kind of infections was reported.

Time frame: Baseline up to Week 51 (21-day dosing schedule) and Week 52 (28-day dosing schedule)

Duration of Participants on Antibiotics for Treatment of Any Kind of Infection

Duration of participants on antibiotics for treatment of any kind of infection was reported.

Time frame: Baseline up to Week 51 (21-day dosing schedule) and Week 52 (28-day dosing schedule)

Duration of Missed School/Work/Other Major Activities Due to Infections

Duration of missed school/work/other major activities due to infections was reported.

Time frame: Baseline up to Week 51 (21-day dosing schedule) and Week 52 (28-day dosing schedule)

Pediatric Quality of Life Inventory (PedsQL) Score

23-item PedsQL generic core scales was a modular approach to measure health-related Quality of Life (QoL) in healthy children, adolescents and those with acute and chronic health conditions. The total scale score (23 items) consisted of Physical Health Summary Score (8 items) and Psychosocial Health SummaryScore (15 items). Physical health summary included Physical Functioning (8 items) and Psychosocial health summary score included Emotional Functioning (5 items), Social Functioning (5 items) and School Functioning (5 items). Items were scored on a 5 point Likert-type response scale: 0=never a problem; 1=almost never a problem; 2=sometimes a problem; 3=often a problem; and 4=almost always a problem). Once scored, items were reverse scored and linearly transformed to a 0-100 scale, where higher scores indicated better QoL. The overall range for total PedsQL score (23 items) was 0 to 100, with higher score indicated better QoL. Data for 18-25 years and \>25 years age group was reported.

Time frame: Baseline, Week 24 (21-day dosing schedule and 28-day dosing schedule), Week 51 (21-day dosing schedule) and Week 52 (28-day dosing schedule)

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs

An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a study drug which may or may not have a causal relationship with the study drug. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life- threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAE was defined as an AE with an onset that occurs after receiving study drug. Any TEAE included participants with both serious and non-serious TEAEs.

Time frame: Baseline up to Week 51 (21-day dosing schedule) and Week 52 (28-day dosing schedule)

Number of TEAEs and Serious TEAEs

An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a study drug which may or may not have a causal relationship with the study drug. A SAE was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life- threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. A TEAE was defined as an AE with an onset that occurs after receiving study drug. Number of TEAEs and Serious TEAEs were reported.

Time frame: Baseline up to Week 51 (21-day dosing schedule) and Week 52 (28-day dosing schedule)

Number of Drug Related Infusion Adverse Events (AEs)

An AE was defined as any untoward medical occurrence in a participant administered a study drug which may or may not have a causal relationship with the study drug. Number of drug related infusion AEs were reported.

Time frame: Baseline up to Week 51 (21-day dosing schedule) and Week 52 (28-day dosing schedule)

Percentage of Participants Who Experienced at Least One Drug Related Infusion Adverse Events (AEs)

Percentage of participants who experienced at least one drug related infusion AEs were reported.

Time frame: Baseline up to Week 51 (21-day dosing schedule) and Week 52 (28-day dosing schedule)

Number of Infusions With Decreased Infusion Rate Due to Adverse Events (AEs)

Number of infusions with decreased infusion rate due to AEs were reported.

Time frame: Baseline up to Week 51 (21-day dosing schedule) and Week 52 (28-day dosing schedule)

Number of Infusions With One or More Infusion Associated Adverse Events (AEs)

The number of infusions with one or more infusion associated AEs were reported collectively for 21 and 28-day dosing schedule up to Week 52.

Time frame: Baseline up to Week 52

Number of Participants With Clinically Significant Changes From Baseline in Vital Signs

Vital signs included body temperature, systolic and diastolic blood pressure, heart rate and weight. The systolic and diastolic blood pressure and pulse rate was measured after the participants have in a rested at least 3 minutes in seated position. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in vital signs were reported.

Time frame: Baseline up to Week 51 (21-day dosing schedule) and Week 52 (28-day dosing schedule)

Number of Participants With Clinically Significant Changes From Baseline in Physical Examinations

Physical examination included the examination of general appearance, skin, neck, eyes, ears, nose, throat, cardiovascular assessment including rhythm, and presence of other cardiac abnormalities (for example gallops, murmurs, cardiomegaly), respiratory system, gastrointestinal system, genitourinary system and musculoskeletal system. Clinical significance was decided by the investigator. The number of participants with clinically significant changes from baseline in physical examination were reported.

Time frame: Baseline up to Week 51 (21-day dosing schedule) and Week 52 (28-day dosing schedule)

Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters

Laboratory parameters included chemistry, hematology and urinalysis. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in laboratory parameters were reported.

Time frame: Baseline up to Week 51 (21-day dosing schedule) and Week 52 (28-day dosing schedule)

Number of Participants With Positive Coomb's Test at Week 16 (28-day Dosing Schedule) and Week 18 (21-day Dosing Schedule)

Intravascular hemolysis testing was performed by using coomb's test. The coomb's assessment was performed at a central laboratory.

Time frame: At Week 16 (28-day dosing schedule) and Week 18 (21-day dosing schedule)

Number of Participants With Positive Urine Hemosiderin Test

Number of participants with positive urine hemosiderin test were reported.

Time frame: At Week 16 (28-day dosing schedule) and Week 18 (21-day dosing schedule)

Number of Participants With Abnormal Plasma-free Haemoglobin Level

Number of participants with plasma-free haemoglobin level more than or equal to (\>=) 69 milligrams per deciliter (mg/dL) were consisdered as abormal and were reported.

Time frame: At Week 16 (28-day dosing schedule) and Week 18 (21-day dosing schedule)

Number of Participants With Abnormal Serum Haptoglobin Level

Number of participants with abnormal serum haptoglobin level were reported.

Time frame: At Week 16 (28-day dosing schedule) and Week 18 (21-day dosing schedule)

Maximum Observed Serum Concentration (Cmax) of Total Immunoglobulin G (IgG)

Cmax was obtained directly from the concentration versus time curve. Both baseline corrected and un-corrected data was reported.