Phase 3
N=47
Clinical Assessment of Pharmacokinetics, Efficacy, and Safety of 10% IVIg in PID Patients
Primary Immunodeficiency Disease
Bottom Line
View on ClinicalTrials.gov: NCT03961009 ↗Enrolled (actual)
47
Serious AEs
8.5%
Results posted
Jan 2022
Primary outcome: Primary: Incidence Rate of Acute Serious Bacterial Infections (ABSIs) — 0.0; 0.0 infections per participant-year
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Kedrion IVIG 10% (Biological)
- Age
- Pediatric, Adult, Older Adult · 2+ yrs
- Sex
- All
- Sponsor
- Kedrion S.p.A.
- Primary completion
- Dec 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Incidence Rate of Acute Serious Bacterial Infections (ABSIs) |
0.0; 0.0 | — |
| SECONDARY Serum Immunoglobulin G (IgG) Trough Levels |
10.317; 11.433; 10.297 | — |
| SECONDARY Immunoglobulin G (IgG) Subclasses Levels (IgG1, IgG2, IgG3, IgG4) |
5.798; 5.605; 5.968; 5.679; 5.979; 5.634 | — |
| SECONDARY Number of Participants With Total Immunoglobulin G (IgG) Trough Levels Less Than or Equal to (<=) 6 Grams/Liter (g/L) Criteria |
1 | — |
| SECONDARY Anti-Tetanus Toxoid Antibody Levels |
2.526; 2.589; 2.654; 2.345; 2.643; 2.207 | — |
| SECONDARY Anti-Pneumococcal Capsular Polysaccharide Antibody Levels |
2.66; 1.55; 4.89; 1.66; 4.74; 1.49 | — |
| SECONDARY Anti-Measles Antibody Levels |
— | — |
| SECONDARY Anti-Haemophilus Influenza Type B Antibody Levels |
2.010; 2.547; 2.489; 2.277; 2.888; 2.183 | — |
| SECONDARY Incidence Rate of Any Infection Other Than Acute Serious Bacterial Infections |
4.4; 1.6 | — |
| SECONDARY Duration of Any Infection Other Than Acute Serious Bacterial Infections |
41.0; 24.9 | — |
| SECONDARY Incidence Rate of Fever Episodes |
0.0; 0.2 | — |
| SECONDARY Duration of Fever Episodes in Participants |
3.0 | — |
| SECONDARY Duration of Overall Participants Hospitalization |
6.0; 3.3 | — |
| SECONDARY Duration of Participants Hospitalization Due to Infection |
— | — |
| SECONDARY Incidence Rate of Antibiotics Episodes for Treatment of Any Kind of Infections |
3.8; 2.1 | — |
| SECONDARY Duration of Participants on Antibiotics for Treatment of Any Kind of Infection |
13.1; 13.3 | — |
| SECONDARY Duration of Missed School/Work/Other Major Activities Due to Infections |
25.3; 4.7 | — |
| SECONDARY Pediatric Quality of Life Inventory (PedsQL) Score |
87.5; 68.5; 58.7; 100.0; 100.0; 76.2 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs |
8; 38; 1; 3 | — |
| SECONDARY Number of TEAEs and Serious TEAEs |
81; 324; 1; 4 | — |
| SECONDARY Number of Drug Related Infusion Adverse Events (AEs) |
3; 60 | — |
| SECONDARY Percentage of Participants Who Experienced at Least One Drug Related Infusion Adverse Events (AEs) |
25.0; 43.6 | — |
| SECONDARY Number of Infusions With Decreased Infusion Rate Due to Adverse Events (AEs) |
0; 9 | — |
| SECONDARY Number of Infusions With One or More Infusion Associated Adverse Events (AEs) |
80 | — |
| SECONDARY Number of Participants With Clinically Significant Changes From Baseline in Vital Signs |
0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Changes From Baseline in Physical Examinations |
0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters |
3; 7; 1; 5; 2; 4 | — |
| SECONDARY Number of Participants With Positive Coomb's Test at Week 16 (28-day Dosing Schedule) and Week 18 (21-day Dosing Schedule) |
14; 4 | — |
| SECONDARY Number of Participants With Positive Urine Hemosiderin Test |
0; 0 | — |
| SECONDARY Number of Participants With Abnormal Plasma-free Haemoglobin Level |
10; 2 | — |
| SECONDARY Number of Participants With Abnormal Serum Haptoglobin Level |
10; 0 | — |
| SECONDARY Maximum Observed Serum Concentration (Cmax) of Total Immunoglobulin G (IgG) |
1280; 1520; 2300; 2680 | — |
| SECONDARY Elimination Half-Life (t1/2) of Total IgG |
158; 107; 896; 587 | — |
| SECONDARY Area Under the Serum Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) of Total IgG |
9520; 8380; 37300; 31700 | — |
| SECONDARY Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Total IgG |
2710.991; 2435.562; 22065.3148; 18292.68 | — |
| SECONDARY Area Under the Serum Concentration-Time Curve During a Dosing Interval (AUCtau) of Total IgG |
9840; 8860; 38000; 34000 | — |
| SECONDARY Volume of Distribution (Vd) of Total IgG |
0.532; 0.563; 0.697; 0.667 | — |
| SECONDARY Steady State Clearance (CLss) of Total IgG |
0.0559; 0.0763; 0.0140; 0.0193 | — |
| SECONDARY Minimum Observed Serum Concentration (Cmin) of Total IgG |
0.00; 0.00; 994; 1140 | — |
| SECONDARY Time to Reach the Maximum Serum Concentration (Tmax) of Total IgG |
0.515; 0.530; 0.515; 0.530 | — |
| SECONDARY Elimination Rate Constant (Kel) of Total IgG |
0.0048; 0.00743; 0.000845; 0.00119 | — |
| SECONDARY Average Concentration of Total IgG Over the Dosing Interval (Cavg) |
354; 424; 1370; 1630 | — |
| SECONDARY Percentage Peak Trough Fluctuation of Total IgG |
364; 360; 94.3; 95.0 | — |
| SECONDARY Maximum Observed Serum Concentration (Cmax) of Antigen-Specific Tetanus Toxoid Antibodies |
6.533; 7.400 | — |
| SECONDARY Elimination Half-Life (t1/2) of Antigen-Specific Tetanus Toxoid Antibodies |
618.97; 1097.75 | — |
| SECONDARY Area Under the Serum Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) of Antigen-Specific Tetanus Toxoid Antibodies |
2037.7497; 1805.9758 | — |
| SECONDARY Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Antigen-Specific Tetanus Toxoid Antibodies |
4171.4977; 10142.0162 | — |
| SECONDARY Area Under the Serum Concentration-Time Curve During a Dosing Interval (AUCtau) of Antigen-Specific Tetanus Toxoid Antibodies |
1997.8829; 1934.6533 | — |
| SECONDARY Volume of Distribution (Vd) of Antigen-Specific Tetanus Toxoid Antibodies |
263.3132; 688.4792 | — |
| SECONDARY Steady State Clearance (CLss) of Antigen-Specific Tetanus Toxoid Antibodies |
0.2741; 0.3724 | — |
| SECONDARY Minimum Observed Serum Concentration (Cmin) of Antigen-Specific Tetanus Toxoid Antibodies |
1.833; 2.240 | — |
| SECONDARY Time to Reach the Maximum Serum Concentration (Tmax) of Antigen-Specific Tetanus Toxoid Antibodies |
2.000; 70.450 | — |
| SECONDARY Elimination Rate Constant (Kel) of Antigen-Specific Tetanus Toxoid Antibodies |
0.0014; 0.0011 | — |
| SECONDARY Average Concentration of Antigen-Specific Tetanus Toxoid Antibodies Over the Dosing Interval (Cavg) |
2.9730; 3.8386 | — |
| SECONDARY Percentage Peak Trough Fluctuation of Antigen-Specific Tetanus Toxoid Antibodies |
154.7237; 145.9127 | — |
| SECONDARY Maximum Observed Serum Concentration (Cmax) of Antigen-Specific Haemophilus Influenza Type B Antibodies |
0.682; 0.787 | — |
| SECONDARY Elimination Half-Life (t1/2) of Antigen-Specific Haemophilus Influenza Type B Antibodies |
682; 364 | — |
| SECONDARY Area Under the Serum Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) of Antigen-Specific Haemophilus Influenza Type B Antibodies |
9.80; 8.80 | — |
| SECONDARY Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Antigen-Specific Haemophilus Influenza Type B Antibodies |
5087.4141; 4223.1698 | — |
| SECONDARY Area Under the Serum Concentration-Time Curve During a Dosing Interval (AUCtau) of Antigen-Specific Haemophilus Influenza Type B Antibodies |
9.80; 9.90 | — |
| SECONDARY Volume of Distribution (Vd) of Antigen-Specific Haemophilus Influenza Type B Antibodies |
245966.4231; 182273.0408 | — |
| SECONDARY Steady State Clearance (CLss) of Antigen-Specific Haemophilus Influenza Type B Antibodies |
253.5539; 299.5030 | — |
| SECONDARY Minimum Observed Serum Concentration (Cmin) of Antigen-Specific Haemophilus Influenza Type B Antibodies |
0.215; 0.225 | — |
| SECONDARY Time to Reach the Maximum Serum Concentration (Tmax) of Antigen-Specific Haemophilus Influenza Type B Antibodies |
0.500; 2.02 | — |
| SECONDARY Terminal Elimination Rate Constant (Lambda z) of Antigen-Specific Haemophilus Influenza Type B Antibodies |
0.00148; 0.00192 | — |
| SECONDARY Average Concentration of Antigen-Specific Haemophilus Influenza Type B Antibodies Over the Dosing Interval (Cavg) |
0.352; 0.474 | — |
| SECONDARY Percentage Peak Trough Fluctuation of Antigen-Specific Haemophilus Influenza Type B Antibodies |
141; 88.1 | — |
| SECONDARY Maximum Observed Serum Concentration (Cmax) of Anti-pneumococcal Capsular Polysaccharide (Overall SP Serotypes) |
3.478; 1.256; 20.378; 4.350; 7.767; 3.822 | — |
| SECONDARY Elimination Half-Life (t1/2) of Anti-pneumococcal Capsular Polysaccharide (Overall SP Serotypes) |
533.06; 415.27; 737.33; 568.11; 794.76; 943.63 | — |
| SECONDARY Area Under the Serum Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) of Anti-pneumococcal Capsular Polysaccharide (Overall SP Serotypes) |
1267.2703; 481.8080; 7680.6757; 1707.2987; 3264.5178; 1462.1037 | — |
| SECONDARY Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Anti-pneumococcal Capsular Polysaccharide (Overall SP Serotypes) |
835.7493; 815.5984; 706.0824; 753.3039; 871.0663; 494.5129 | — |
| SECONDARY Area Under the Serum Concentration-Time Curve During a Dosing Interval (AUCtau) of Anti-pneumococcal Capsular Polysaccharide (Overall SP Serotypes) |
1295.2208; 496.5246; 7938.1617; 1128.6509; 2051.7286; 1437.7169 | — |
| SECONDARY Volume of Distribution (Vd) of of Anti-pneumococcal Capsular Polysaccharide (Overall SP Serotypes) |
329057.3200; 341197.1700; 231539.8050; 226738.9500; 342896.0600; 526016.9000 | — |
| SECONDARY Steady State Clearance (CLss) of Anti-pneumococcal Capsular Polysaccharide Antibodies (Overall SP Serotypes) |
860.4600; 862.3000; 604.0850; 705.5700; 854.8300; 1441.7300 | — |
| SECONDARY Minimum Observed Serum Concentration (Cmin) of Anti-pneumococcal Capsular Polysaccharide (Overall SP Serotypes) |
1.167; 0.528; 8.361; 2.328; 3.783; 1.656 | — |
| SECONDARY Time to Reach the Maximum Serum Concentration (Tmax) of Anti-pneumococcal Capsular Polysaccharide (Overall SP Serotypes) |
0.542; 0.517; 1.417; 1.992; 0.642; 1.458 | — |
| SECONDARY Elimination Rate Constant (Kel) of Anti-pneumococcal Capsular Polysaccharide (Overall SP Serotypes) |
0.0016; 0.0017; 0.0011; 0.0014; 0.0010; 0.0010 | — |
| SECONDARY Average Concentration of Anti-pneumococcal Capsular Polysaccharide the Dosing Interval (Cavg) (Overall SP Serotypes) |
1.9274; 0.7389; 11.8127; 1.7723; 3.2992; 2.2719 | — |
| SECONDARY Percentage Peak Trough Fluctuation of Anti-pneumococcal Capsular Polysaccharide (Overall SP Serotypes) |
128.3177; 125.2166; 107.5731; 103.6118; 110.9054; 105.2306 | — |
Summary
The purpose of this study was to assess efficacy and safety of Kedrion Immunoglobulin 10% (KIg10) in participants with Primary Immunodeficiency (PID).
Eligibility Criteria
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+ = 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 ( 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
Data sourced from ClinicalTrials.gov (NCT03961009). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.