Healthy
Conditions
Brief summary
A Phase 1, Randomized, Double-blind, Three-arm, Parallel Group, Single-dose Study to Compare the Pharmacokinetics and Safety of Three Formulations of Omalizumab (CT-P39, EU-approved Xolair, and US-licensed Xolair) in Healthy Subjects
Interventions
BIOLOGICALCT-P39
150 mg/mL, Solution for injection in PFS
BIOLOGICALEU-approved Xolair
150 mg/mL, Solution for injection in PFS
BIOLOGICALUS-licensed Xolair
150 mg/mL, Solution for injection in PFS
Sponsors
Celltrion
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy subject (male or female) between the ages of 18 and 55 years. * Subject with a body weight of \> 40 kg and ≤ 90 kg and a BMI between 18.0 kg/m2 and 32.0 kg/m2(both inclusive). * Subject with a total IgE level of ≤ 100 IU/mL.
Exclusion criteria
* Subject has a medical history and/or current presence of disease including one or more of the allergic reaction.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Outcome Measures [AUC0-inf] for Part 2 | up to day 127 | Area Under the concentration-time Curve from time zero to infinity (AUC0-inf) of CT-P39, EU-approved Xolair, and US-licensed Xolair in healthy subjects (CT-P39 to EU-approved Xolair, CT-P39 to US-licensed Xolair, and EU-approved Xolair to US-licensed Xolair) |
| Pharmacokinetic Outcome Measures [AUC0-last] for Part 2 | up to day 127 | Area Under the concentration-time Curve from time zero to the last quantifiable concentration (AUC0-last) of CT-P39, EU-approved Xolair, and US-licensed Xolair in healthy subjects (CT-P39 to EU-approved Xolair, CT-P39 to US-licensed Xolair, and EU-approved Xolair to US-licensed Xolair) |
| Pharmacokinetic Outcome Measures [Cmax] for Part 2 | up to day 127 | Maximum serum concentration (Cmax) of CT-P39, EU-approved Xolair, and US-licensed Xolair in healthy subjects (CT-P39 to EU-approved Xolair, CT-P39 to US-licensed Xolair, and EU-approved Xolair to US-licensed Xolair) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamic Outcome Measures [Tmin of Free IgE] for Part 1 & Part 2 | Up to day 127 | To assess the Time to Cmin (Tmin) of Free IgE in CT-P39, EU-approved Xolair, and US-licensed Xolair in healthy subjects |
| Pharmacokinetic Outcome Measures [Tmax] for Part 1& Part 2 | up to day 127 | To assess Time to Cmax (Tmax) of CT-P39, EU-approved Xolair, and US-licensed Xolair in healthy subjects |
| Pharmacodynamic Outcome Measures [Tmax of Total IgE] for Part 1 & Part 2 | up to day 127 | To assess the Time to Cmax (Tmax) of total IgE in CT-P39, EU-approved Xolair, and US-licensed Xolair in healthy subjects |
| Pharmacodynamic Outcome Measures [Cmax of Total IgE] for Part 1 & Part 2 | up to day 127 | To assess the maximum observed concentration (Cmax) of total IgE in CT-P39, EU-approved Xolair, and US-licensed Xolair in healthy subjects |
| Pharmacokinetic Outcome Measures [t1/2] for Part 1& Part 2 | up to day 127 | To assess Terminal half-life (t1/2) of CT-P39, EU-approved Xolair, and US-licensed Xolair in healthy subjects |
| Pharmacodynamics Outcome Measures [Cmin of Free IgE] for Part 1 & Part 2 | up to day 127 | To assess the minimum observed concentration (Cmin) of Free IgE in CT-P39, EU-approved Xolair, and US-licensed Xolair in healthy subjects |
Countries
Australia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CT-P39 (Part 1) Healthy subjects were administered single subcutaneous (SC) injection of CT-P39 via pre-filled syringe (PFS).
CT-P39: 150 mg/mL Solution for injection. | 15 |
| EU-approved Xolair (Part 1) Healthy subjects were administered single subcutaneous (SC) injection of EU-approved Xolair via pre-filled syringe (PFS).
EU-approved Xolair: 150 mg/mL Solution for injection. | 15 |
| CT-P39 (Part 2) Healthy subjects were administered single subcutaneous (SC) injection of CT-P39 via pre-filled syringe (PFS).
CT-P39: 150 mg/mL Solution for injection. | 47 |
| EU-approved Xolair (Part 2) Healthy subjects were administered single subcutaneous (SC) injection of EU-approved Xolair via pre-filled syringe (PFS).
EU-approved Xolair: 150 mg/mL Solution for injection. | 49 |
| US-licensed Xolair (Part 2) Healthy subjects were administered single subcutaneous (SC) injection of US-licensed Xolair via pre-filled syringe (PFS).
US-licensed Xolair: 150 mg/mL Solution for injection. | 50 |
| Total | 176 |
Baseline characteristics
| Characteristic | US-licensed Xolair (Part 2) | Total | CT-P39 (Part 1) | EU-approved Xolair (Part 1) | CT-P39 (Part 2) | EU-approved Xolair (Part 2) |
|---|---|---|---|---|---|---|
| Age, Continuous | 30.3 years STANDARD_DEVIATION 10.09 | 29.6 years STANDARD_DEVIATION 9.99 | 26.7 years STANDARD_DEVIATION 6.31 | 26.9 years STANDARD_DEVIATION 9.11 | 28.2 years STANDARD_DEVIATION 8.81 | 32.1 years STANDARD_DEVIATION 11.65 |
| Body mass index at screening | 23.71 kg/m2 STANDARD_DEVIATION 2.98 | 23.54 kg/m2 STANDARD_DEVIATION 2.866 | 22.93 kg/m2 STANDARD_DEVIATION 2.525 | 23.65 kg/m2 STANDARD_DEVIATION 2.306 | 23.90 kg/m2 STANDARD_DEVIATION 3.042 | 23.19 kg/m2 STANDARD_DEVIATION 2.864 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 30 Participants | 5 Participants | 5 Participants | 6 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 134 Participants | 9 Participants | 7 Participants | 40 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 12 Participants | 1 Participants | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized American Indian or Alaska native | 0 Participants | 3 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 8 Participants | 21 Participants | 0 Participants | 0 Participants | 7 Participants | 6 Participants |
| Race/Ethnicity, Customized Australian Aborigine/Torres Strait Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 4 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 8 Participants | 2 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 40 Participants | 138 Participants | 12 Participants | 12 Participants | 36 Participants | 38 Participants |
| Region of Enrollment Australia | 50 participants | 176 participants | 15 participants | 15 participants | 47 participants | 49 participants |
| Sex: Female, Male Female | 30 Participants | 101 Participants | 8 Participants | 8 Participants | 28 Participants | 27 Participants |
| Sex: Female, Male Male | 20 Participants | 75 Participants | 7 Participants | 7 Participants | 19 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 | 0 / 47 | 0 / 49 | 0 / 50 |
| other Total, other adverse events | 4 / 15 | 7 / 15 | 20 / 47 | 26 / 49 | 31 / 50 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 1 / 47 | 0 / 49 | 0 / 50 |
Outcome results
Primary
Pharmacokinetic Outcome Measures [AUC0-inf] for Part 2
Area Under the concentration-time Curve from time zero to infinity (AUC0-inf) of CT-P39, EU-approved Xolair, and US-licensed Xolair in healthy subjects (CT-P39 to EU-approved Xolair, CT-P39 to US-licensed Xolair, and EU-approved Xolair to US-licensed Xolair)
Time frame: up to day 127
Population: PK set: all randomly assigned subjects who receive a complete dose of study drug and provide at least one post-treatment serum concentration above the lower limit of quantification for omalizumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-P39 (Part 2) | Pharmacokinetic Outcome Measures [AUC0-inf] for Part 2 | 910.9 day*μg/mL | Standard Deviation 278.57 |
| EU-approved Xolair (Part 2) | Pharmacokinetic Outcome Measures [AUC0-inf] for Part 2 | 897.7 day*μg/mL | Standard Deviation 270.25 |
| US-licensed Xolair (Part 2) | Pharmacokinetic Outcome Measures [AUC0-inf] for Part 2 | 926.3 day*μg/mL | Standard Deviation 273.3 |
Comparison: The statistical analysis of the log-transformed primary endpoints was based on an ANCOVA model with treatment as fixed effect and baseline body weight, total IgE level and sex as covariates.90% CI: [95.91, 116.31]
Comparison: The statistical analysis of the log-transformed primary endpoints was based on an ANCOVA model with treatment as fixed effect and baseline body weight, total IgE level and sex as covariates.90% CI: [89.76, 108.58]
Comparison: The statistical analysis of the log-transformed primary endpoints was based on an ANCOVA model with treatment as fixed effect and baseline body weight, total IgE level and sex as covariates.90% CI: [85.09, 102.68]
Primary
Pharmacokinetic Outcome Measures [AUC0-last] for Part 2
Area Under the concentration-time Curve from time zero to the last quantifiable concentration (AUC0-last) of CT-P39, EU-approved Xolair, and US-licensed Xolair in healthy subjects (CT-P39 to EU-approved Xolair, CT-P39 to US-licensed Xolair, and EU-approved Xolair to US-licensed Xolair)
Time frame: up to day 127
Population: PK set: all randomly assigned subjects who receive a complete dose of study drug and provide at least one post-treatment serum concentration above the lower limit of quantification for omalizumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-P39 (Part 2) | Pharmacokinetic Outcome Measures [AUC0-last] for Part 2 | 846 day*μg/mL | Standard Deviation 251.87 |
| EU-approved Xolair (Part 2) | Pharmacokinetic Outcome Measures [AUC0-last] for Part 2 | 843.8 day*μg/mL | Standard Deviation 248.04 |
| US-licensed Xolair (Part 2) | Pharmacokinetic Outcome Measures [AUC0-last] for Part 2 | 850.0 day*μg/mL | Standard Deviation 213.13 |
Comparison: The statistical analysis of the log-transformed primary endpoints was based on an ANCOVA model with treatment as fixed effect and baseline body weight, total IgE level and sex as covariates.90% CI: [94.96, 113.89]
Comparison: The statistical analysis of the log-transformed primary endpoints was based on an ANCOVA model with treatment as fixed effect and baseline body weight, total IgE level and sex as covariates.90% CI: [90.79, 108.61]
Comparison: The statistical analysis of the log-transformed primary endpoints was based on an ANCOVA model with treatment as fixed effect and baseline body weight, total IgE level and sex as covariates.90% CI: [87.36, 104.37]
Primary
Pharmacokinetic Outcome Measures [Cmax] for Part 2
Maximum serum concentration (Cmax) of CT-P39, EU-approved Xolair, and US-licensed Xolair in healthy subjects (CT-P39 to EU-approved Xolair, CT-P39 to US-licensed Xolair, and EU-approved Xolair to US-licensed Xolair)
Time frame: up to day 127
Population: PK set: all randomly assigned subjects who receive a complete dose of study drug and provide at least one post-treatment serum concentration above the lower limit of quantification for omalizumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-P39 (Part 2) | Pharmacokinetic Outcome Measures [Cmax] for Part 2 | 20.08 μg/mL | Standard Deviation 5.994 |
| EU-approved Xolair (Part 2) | Pharmacokinetic Outcome Measures [Cmax] for Part 2 | 18.24 μg/mL | Standard Deviation 4.9981 |
| US-licensed Xolair (Part 2) | Pharmacokinetic Outcome Measures [Cmax] for Part 2 | 19.43 μg/mL | Standard Deviation 5.4159 |
Comparison: The statistical analysis of the log-transformed primary endpoints was based on an ANCOVA model with treatment as fixed effect and baseline body weight, total IgE level and sex as covariates.90% CI: [103.15, 124.11]
Comparison: The statistical analysis of the log-transformed primary endpoints was based on an ANCOVA model with treatment as fixed effect and baseline body weight, total IgE level and sex as covariates.90% CI: [94.83, 113.8]
Comparison: The statistical analysis of the log-transformed primary endpoints was based on an ANCOVA model with treatment as fixed effect and baseline body weight, total IgE level and sex as covariates.90% CI: [83.87, 100.52]
Secondary
Pharmacodynamic Outcome Measures [Cmax of Total IgE] for Part 1 & Part 2
To assess the maximum observed concentration (Cmax) of total IgE in CT-P39, EU-approved Xolair, and US-licensed Xolair in healthy subjects
Time frame: up to day 127
Population: PD set: all randomly assigned subjects who receive a complete dose of study drug and have at least one post-treatment free IgE or total IgE concentration above the lower limit of quantification.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-P39 (Part 2) | Pharmacodynamic Outcome Measures [Cmax of Total IgE] for Part 1 & Part 2 | 241.5333 IU/mL | Standard Deviation 156.50234 |
| EU-approved Xolair (Part 2) | Pharmacodynamic Outcome Measures [Cmax of Total IgE] for Part 1 & Part 2 | 165.2000 IU/mL | Standard Deviation 122.59702 |
| US-licensed Xolair (Part 2) | Pharmacodynamic Outcome Measures [Cmax of Total IgE] for Part 1 & Part 2 | 245.2391 IU/mL | Standard Deviation 223.24856 |
| EU-approved Xolair (Part 2) | Pharmacodynamic Outcome Measures [Cmax of Total IgE] for Part 1 & Part 2 | 174.2857 IU/mL | Standard Deviation 145.17432 |
| US-licensed Xolair (Part 2) | Pharmacodynamic Outcome Measures [Cmax of Total IgE] for Part 1 & Part 2 | 219.5714 IU/mL | Standard Deviation 187.41287 |
Secondary
Pharmacodynamic Outcome Measures [Tmax of Total IgE] for Part 1 & Part 2
To assess the Time to Cmax (Tmax) of total IgE in CT-P39, EU-approved Xolair, and US-licensed Xolair in healthy subjects
Time frame: up to day 127
Population: PD set: all randomly assigned subjects who receive a complete dose of study drug and have at least one post-treatment free IgE or total IgE concentration above the lower limit of quantification.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CT-P39 (Part 2) | Pharmacodynamic Outcome Measures [Tmax of Total IgE] for Part 1 & Part 2 | 28.263 day |
| EU-approved Xolair (Part 2) | Pharmacodynamic Outcome Measures [Tmax of Total IgE] for Part 1 & Part 2 | 28.167 day |
| US-licensed Xolair (Part 2) | Pharmacodynamic Outcome Measures [Tmax of Total IgE] for Part 1 & Part 2 | 28.191 day |
| EU-approved Xolair (Part 2) | Pharmacodynamic Outcome Measures [Tmax of Total IgE] for Part 1 & Part 2 | 28.156 day |
| US-licensed Xolair (Part 2) | Pharmacodynamic Outcome Measures [Tmax of Total IgE] for Part 1 & Part 2 | 28.087 day |
Secondary
Pharmacodynamic Outcome Measures [Tmin of Free IgE] for Part 1 & Part 2
To assess the Time to Cmin (Tmin) of Free IgE in CT-P39, EU-approved Xolair, and US-licensed Xolair in healthy subjects
Time frame: Up to day 127
Population: PD set: all randomly assigned subjects who receive a complete dose of study drug and have at least one post-treatment free IgE or total IgE concentration above the lower limit of quantification.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CT-P39 (Part 2) | Pharmacodynamic Outcome Measures [Tmin of Free IgE] for Part 1 & Part 2 | 3.000 day |
| EU-approved Xolair (Part 2) | Pharmacodynamic Outcome Measures [Tmin of Free IgE] for Part 1 & Part 2 | 5.196 day |
| US-licensed Xolair (Part 2) | Pharmacodynamic Outcome Measures [Tmin of Free IgE] for Part 1 & Part 2 | 3.000 day |
| EU-approved Xolair (Part 2) | Pharmacodynamic Outcome Measures [Tmin of Free IgE] for Part 1 & Part 2 | 5.051 day |
| US-licensed Xolair (Part 2) | Pharmacodynamic Outcome Measures [Tmin of Free IgE] for Part 1 & Part 2 | 3.002 day |
Secondary
Pharmacodynamics Outcome Measures [Cmin of Free IgE] for Part 1 & Part 2
To assess the minimum observed concentration (Cmin) of Free IgE in CT-P39, EU-approved Xolair, and US-licensed Xolair in healthy subjects
Time frame: up to day 127
Population: PD set: all randomly assigned subjects who receive a complete dose of study drug and have at least one post-treatment free IgE or total IgE concentration above the lower limit of quantification.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-P39 (Part 2) | Pharmacodynamics Outcome Measures [Cmin of Free IgE] for Part 1 & Part 2 | 3.1538 IU/mL | Standard Deviation 1.12963 |
| EU-approved Xolair (Part 2) | Pharmacodynamics Outcome Measures [Cmin of Free IgE] for Part 1 & Part 2 | 3.4613 IU/mL | Standard Deviation 1.43457 |
| US-licensed Xolair (Part 2) | Pharmacodynamics Outcome Measures [Cmin of Free IgE] for Part 1 & Part 2 | 3.5267 IU/mL | Standard Deviation 1.45275 |
| EU-approved Xolair (Part 2) | Pharmacodynamics Outcome Measures [Cmin of Free IgE] for Part 1 & Part 2 | 3.5590 IU/mL | Standard Deviation 1.56235 |
| US-licensed Xolair (Part 2) | Pharmacodynamics Outcome Measures [Cmin of Free IgE] for Part 1 & Part 2 | 3.7002 IU/mL | Standard Deviation 1.69613 |
Secondary
Pharmacokinetic Outcome Measures [t1/2] for Part 1& Part 2
To assess Terminal half-life (t1/2) of CT-P39, EU-approved Xolair, and US-licensed Xolair in healthy subjects
Time frame: up to day 127
Population: PK set: all randomly assigned subjects who receive a complete dose of study drug and provide at least one post-treatment serum concentration above the lower limit of quantification for omalizumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-P39 (Part 2) | Pharmacokinetic Outcome Measures [t1/2] for Part 1& Part 2 | 29.75 day | Standard Deviation 3.9477 |
| EU-approved Xolair (Part 2) | Pharmacokinetic Outcome Measures [t1/2] for Part 1& Part 2 | 28.77 day | Standard Deviation 5.0315 |
| US-licensed Xolair (Part 2) | Pharmacokinetic Outcome Measures [t1/2] for Part 1& Part 2 | 29.30 day | Standard Deviation 9.5158 |
| EU-approved Xolair (Part 2) | Pharmacokinetic Outcome Measures [t1/2] for Part 1& Part 2 | 27.69 day | Standard Deviation 5.5603 |
| US-licensed Xolair (Part 2) | Pharmacokinetic Outcome Measures [t1/2] for Part 1& Part 2 | 28.63 day | Standard Deviation 6.629 |
Secondary
Pharmacokinetic Outcome Measures [Tmax] for Part 1& Part 2
To assess Time to Cmax (Tmax) of CT-P39, EU-approved Xolair, and US-licensed Xolair in healthy subjects
Time frame: up to day 127
Population: PK set: all randomly assigned subjects who receive a complete dose of study drug and provide at least one post-treatment serum concentration above the lower limit of quantification for omalizumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CT-P39 (Part 2) | Pharmacokinetic Outcome Measures [Tmax] for Part 1& Part 2 | 7.178 day |
| EU-approved Xolair (Part 2) | Pharmacokinetic Outcome Measures [Tmax] for Part 1& Part 2 | 7.244 day |
| US-licensed Xolair (Part 2) | Pharmacokinetic Outcome Measures [Tmax] for Part 1& Part 2 | 7.098 day |
| EU-approved Xolair (Part 2) | Pharmacokinetic Outcome Measures [Tmax] for Part 1& Part 2 | 7.306 day |
| US-licensed Xolair (Part 2) | Pharmacokinetic Outcome Measures [Tmax] for Part 1& Part 2 | 7.183 day |