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Phase 3 N=47 Treatment

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

Primary Immunodeficiency Disease

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

OutcomeResultp-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
View full record on ClinicalTrials.gov →

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.

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