Healthy
Conditions
Brief summary
This is a Phase 1, Randomized, Double-blind, Three-arm, Parallel group, Single-dose Study to Compare the Pharmacokinetics and Safety of CT-P17 and Humira (US licensed Humira and EU-approved Humira) in Healthy Subjects
Interventions
BIOLOGICALCT-P17
40 mg/0.4ml (100 mg/mL) administered as a single SC injection via PFS
BIOLOGICALUS-licensed Humira
40 mg/0.4ml (100 mg/mL) administered as a single SC injection via PFS
BIOLOGICALEU-approved Humira
40 mg/0.4ml (100 mg/mL) administered as a single SC injection via 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
19 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy subjects * BMI between 18.0 and 29.9 kg/m2, both inclusive, when rounded to the nearest tenth
Exclusion criteria
* A medical history and/or condition that is considered significant * Clinically significant allergic reactions, hypersensitivity * History or current infection of hepatitis B virus (except for past resolved infection), hepatitis C virus, human immunodeficiency virus, or syphilis * Active or latent Tuberculosis * History of malignancy * Previous monoclonal antibody or fusion protein treatment, or current use of any biologic * Planning to be pregnant or father a child or donate sperm within 5 month after administration * Undergone treatment with an investigational drug or participated in another clinical trial within 90 days or 5 half-lives (whichever is longer)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) | up to Day 71 | Primary endpoints were equivalence of PK between CT-P17 and reference drugs in terms of AUC0-inf, AUC0-last, and Cmax. Blood samples for PK analysis were obtained pre-dose and at 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 192, 336, 504, 672, 1008, 1344, and 1680 hour post-dose. |
| Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) | up to Day 71 | Primary endpoints were equivalence of PK between CT-P17 and reference drugs in terms of AUC0-inf, AUC0-last, and Cmax. Blood samples for PK analysis were obtained pre-dose and at 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 192, 336, 504, 672, 1008, 1344, and 1680 hour post-dose. |
| Maximum Serum Concentration (Cmax) | up to Day 71 | Primary endpoints were equivalence of PK between CT-P17 and reference drugs in terms of AUC0-inf, AUC0-last, and Cmax. Blood samples for PK analysis were obtained pre-dose and at 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 192, 336, 504, 672, 1008, 1344, and 1680 hour post-dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to the Maximum Serum Concentration (Tmax) | up to Day 71 | The secondary objective was to evaluate the additional PK parameters including Tmax and t1/2. Blood samples for PK analysis were obtained pre-dose and at 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 192, 336, 504, 672, 1008, 1344, and 1680 hour post-dose. |
| Terminal Elimination Half-life (t1/2) | up to Day 71 | The secondary objective was to evaluate the additional PK parameters including Tmax and t1/2. Blood samples for PK analysis were obtained pre-dose and at 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 192, 336, 504, 672, 1008, 1344, and 1680 hour post-dose. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CT-P17 a single subcutaneous (SC) injection via pre-filled syringe (PFS)
CT-P17: 40 mg/0.4ml (100 mg/mL) administered as a single SC injection via PFS | 102 |
| US-licensed Humira a single subcutaneous (SC) injection via pre-filled syringe (PFS)
US-licensed Humira: 40 mg/0.4ml (100 mg/mL) administered as a single SC injection via PFS | 102 |
| EU-approved Humira a single subcutaneous (SC) injection via pre-filled syringe (PFS)
EU-approved Humira: 40 mg/0.4ml (100 mg/mL) administered as a single SC injection via PFS | 104 |
| Total | 308 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 3 |
Baseline characteristics
| Characteristic | CT-P17 | Total | EU-approved Humira | US-licensed Humira |
|---|---|---|---|---|
| Age, Continuous | 25.0 years | 26.0 years | 26.0 years | 26.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 102 Participants | 308 Participants | 104 Participants | 102 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 102 Participants | 308 Participants | 104 Participants | 102 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment South Korea | 102 Participants | 308 Participants | 104 Participants | 102 Participants |
| Sex: Female, Male Female | 15 Participants | 44 Participants | 15 Participants | 14 Participants |
| Sex: Female, Male Male | 87 Participants | 264 Participants | 89 Participants | 88 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 102 | 0 / 102 | 0 / 104 |
| other Total, other adverse events | 26 / 102 | 27 / 102 | 27 / 104 |
| serious Total, serious adverse events | 2 / 102 | 0 / 102 | 1 / 104 |
Outcome results
Primary
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf)
Primary endpoints were equivalence of PK between CT-P17 and reference drugs in terms of AUC0-inf, AUC0-last, and Cmax. Blood samples for PK analysis were obtained pre-dose and at 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 192, 336, 504, 672, 1008, 1344, and 1680 hour post-dose.
Time frame: up to Day 71
Population: Pharmacokinetic population (all randomly assigned subjects who received a complete dose of study drug and provided at least 1 post-treatment serum concentration above the lower limit of quantification for adalimumab)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-P17 | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) | 2656.5 h•μg/mL | Standard Deviation 1150.16 |
| US-licensed Humira | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) | 2469.7 h•μg/mL | Standard Deviation 917.47 |
| EU-approved Humira | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) | 2690.6 h•μg/mL | Standard Deviation 943.76 |
Comparison: Statistical analysis of primary PK parameters was performed using an analysis of covariance model (ANCOVA) including covariates for gender, study center, and body weight.90% CI: [97.19, 115.16]
Comparison: Statistical analysis of primary PK parameters was performed using an analysis of covariance model (ANCOVA) including covariates for gender, study center, and body weight.90% CI: [85.29, 100.61]
Comparison: Statistical analysis of primary PK parameters was performed using an analysis of covariance model (ANCOVA) including covariates for gender, study center, and body weight.90% CI: [90.06, 106.63]
Primary
Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last)
Primary endpoints were equivalence of PK between CT-P17 and reference drugs in terms of AUC0-inf, AUC0-last, and Cmax. Blood samples for PK analysis were obtained pre-dose and at 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 192, 336, 504, 672, 1008, 1344, and 1680 hour post-dose.
Time frame: up to Day 71
Population: Pharmacokinetic population (all randomly assigned subjects who received a complete dose of study drug and provided at least 1 post-treatment serum concentration above the lower limit of quantification for adalimumab)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-P17 | Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) | 2372.7 h•μg/mL | Standard Deviation 954.82 |
| US-licensed Humira | Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) | 2185.0 h•μg/mL | Standard Deviation 795.91 |
| EU-approved Humira | Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) | 2394.7 h•μg/mL | Standard Deviation 866.95 |
Comparison: Statistical analysis of primary PK parameters was performed using an analysis of covariance model (ANCOVA) including covariates for gender, study center, and body weight.90% CI: [98.29, 117.13]
Comparison: Statistical analysis of primary PK parameters was performed using an analysis of covariance model (ANCOVA) including covariates for gender, study center, and body weight.90% CI: [86.08, 102.5]
Comparison: Statistical analysis of primary PK parameters was performed using an analysis of covariance model (ANCOVA) including covariates for gender, study center, and body weight.90% CI: [92.42, 109.92]
Primary
Maximum Serum Concentration (Cmax)
Primary endpoints were equivalence of PK between CT-P17 and reference drugs in terms of AUC0-inf, AUC0-last, and Cmax. Blood samples for PK analysis were obtained pre-dose and at 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 192, 336, 504, 672, 1008, 1344, and 1680 hour post-dose.
Time frame: up to Day 71
Population: Pharmacokinetic population (all randomly assigned subjects who received a complete dose of study drug and provided at least 1 post-treatment serum concentration above the lower limit of quantification for adalimumab)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-P17 | Maximum Serum Concentration (Cmax) | 3.619 μg/mL | Standard Deviation 1.3522 |
| US-licensed Humira | Maximum Serum Concentration (Cmax) | 3.556 μg/mL | Standard Deviation 1.1972 |
| EU-approved Humira | Maximum Serum Concentration (Cmax) | 3.660 μg/mL | Standard Deviation 1.2212 |
Comparison: Statistical analysis of primary PK parameters was performed using an analysis of covariance model (ANCOVA) including covariates for gender, study center, and body weight.90% CI: [95.33, 108.89]
Comparison: Statistical analysis of primary PK parameters was performed using an analysis of covariance model (ANCOVA) including covariates for gender, study center, and body weight.90% CI: [91.91, 104.92]
Comparison: Statistical analysis of primary PK parameters was performed using an analysis of covariance model (ANCOVA) including covariates for gender, study center, and body weight.90% CI: [93.69, 106.85]
Secondary
Terminal Elimination Half-life (t1/2)
The secondary objective was to evaluate the additional PK parameters including Tmax and t1/2. Blood samples for PK analysis were obtained pre-dose and at 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 192, 336, 504, 672, 1008, 1344, and 1680 hour post-dose.
Time frame: up to Day 71
Population: Pharmacokinetic population (all randomly assigned subjects who received a complete dose of study drug and provided at least 1 post-treatment serum concentration above the lower limit of quantification for adalimumab)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-P17 | Terminal Elimination Half-life (t1/2) | 340.3 h | Standard Deviation 163.61 |
| US-licensed Humira | Terminal Elimination Half-life (t1/2) | 331.3 h | Standard Deviation 165.05 |
| EU-approved Humira | Terminal Elimination Half-life (t1/2) | 339.5 h | Standard Deviation 151.04 |
Secondary
Time to the Maximum Serum Concentration (Tmax)
The secondary objective was to evaluate the additional PK parameters including Tmax and t1/2. Blood samples for PK analysis were obtained pre-dose and at 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 192, 336, 504, 672, 1008, 1344, and 1680 hour post-dose.
Time frame: up to Day 71
Population: Pharmacokinetic population (all randomly assigned subjects who received a complete dose of study drug and provided at least 1 post-treatment serum concentration above the lower limit of quantification for adalimumab)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CT-P17 | Time to the Maximum Serum Concentration (Tmax) | 167.433 h |
| US-licensed Humira | Time to the Maximum Serum Concentration (Tmax) | 166.833 h |
| EU-approved Humira | Time to the Maximum Serum Concentration (Tmax) | 144.000 h |