Healthy Study Participants
Conditions
Keywords
UCB4940, BKZ, bimekizumab, Bioequivalence, Auto-injector, Healthy study participants
Brief summary
The purpose of the study is to compare the pharmacokinetics (PK), safety and tolerability of a single subcutaneous (sc) dose of bimekizumab (BKZ) when administered using bimekizumab-autoinjector (AI)-2mL presentation versus bimekizumab-AI-2x1mL presentation in healthy study participants.
Interventions
DRUGbimekizumab
Study participants will receive a single dose of bimekizumab (BKZ) administered subcutaneously in the Treatment Period.
Sponsors
UCB Biopharma SRL
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Study participant must be ≥18 years and ≤65 years of age inclusive, at the time of signing the informed consent * Study participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and laboratory tests, during the Screening Period and on admission * Study participant has a body temperature between 35.0°C and 37.5°C, inclusive, at Screening and on admission * Body weight minimum of 50 kg for male and 45 kg for female study participants and a maximum of 100 kg for all study participants, and body mass index (BMI) within the range 18 to 32 kg/m\^2 (inclusive) at the Screening Visit * Male or female. Contraception guidelines (as per the standard UCB contraceptive guideline) will be applicable.
Exclusion criteria
* Study participant has a known hypersensitivity to any components of the bimekizumab (and/or an investigational device) as stated in this protocol * Study participant has an active infection or history of infections as follows: * Any active infection (except common cold) within 14 days prior to Screening Visit * A serious infection, defined as requiring hospitalization or iv anti-infectives within 2 months prior to the Screening Visit * A history of opportunistic, recurrent, or chronic infections that, in the opinion of the Investigator, might cause this study to be detrimental to the study participant. Opportunistic infections are infections caused by uncommon pathogens (eg, pneumocystis jirovecii, cryptococcosis) or unusually severe infections caused by common pathogens (eg, cytomegalovirus, herpes zoster) * Study participant has a history of a positive TB test or evidence of possible TB or latent TB infection at Screening Visit. Refer to Tuberculosis Detection Procedure Guideline for details regarding TB infection status, detection procedures, and the related
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC) for a Single Dose Bimekizumab (BKZ) | Baseline (Day 1 predose) at predefined time points (up to Day 140) | AUC is the area under the plasma concentration-time curve from time 0 (Day 1 predose) to infinity. |
| Area Under the Plasma Concentration-time Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) for a Single Dose Bimekizumab (BKZ) | From Baseline (Day 1 predose) at predefined time points to the last quantifiable concentration (Day 140) | AUC0-t is the area under the plasma concentration-time curve from time zero (Day 1 predose) to the last quantifiable concentration. |
| Maximum Plasma Concentration (Cmax) for a Single Dose Bimekizumab (BKZ) | From Baseline (Day 1 predose) at predefined time points (up to Day 140) | Cmax is a maximum observed plasma concentration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE) From Baseline to End of Safety Follow-Up | From Baseline (Day 1) to end of Safety Follow-Up (up to Day 140) | An AE is any untoward medical occurrence in a patient or clinical study participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAEs are defined as AEs not present prior to the administration of IMP or any unresolved event already present before administration of IMP that worsens in intensity following exposure to study treatment. |
| Time of Occurrence of the Maximum Observed Concentration (Tmax) of a Single Dose Bimekizumab (BKZ) | From Baseline (Day 1 predose) at predefined time points (up to Day 140) | tmax is the time to reach maximum plasma concentration. |
| Percentage of Participants With at Least One Treatment-emergent Serious Adverse Event (SAE) From Baseline to End of Safety Follow-Up | From Baseline (Day 1) to end of Safety Follow-Up (up to Day 140) | A SAE is defined as any untoward medical occurrence that at any dose: a. Results in death, b. Is life-threatening, c. Requires inpatient hospitalization or prolongation of existing hospitalization, d. Results in persistent disability/incapacity, e. Is a congenital anomaly/ birth defect, f. Is an important medical event which based on appropriate medical judgment, jeopardized the study participant and required medical or surgical intervention to prevent any of the above. |
| Apparent Terminal Half-life (t1/2) | From Baseline (Day 1 predose) at predefined time points (up to Day 140) | Apparent terminal half-life as determined via linear regression (slope=-lamdbaz) of the natural log (ln) concentration versus time, for data points in the terminal phase of the concentration time curve (ln2/lambdaz). |
Countries
Germany, United States
Participant flow
Recruitment details
The study started to enroll participants in March 2022 and concluded in January 2023.
Pre-assignment details
The Participant Flow refers to the Safety Set (SS). The SS consisted of all study participants who randomized and received full or partial investigational medicinal product (IMP) according to the treatment the study participants actually received.
Participants by arm
| Arm | Count |
|---|---|
| Bimekizumab-AI-2mL (Test) Participants received a single dose of bimekizumab 320 mg (1x320 mg) administered as a subcutaneous injection using a 2 mL auto-injector (AI) on Day 1 of the study. | 60 |
| Bimekizumab-AI-2x1mL (Reference) Participants received a single dose of bimekizumab 320 mg (2x160 mg) administered as a subcutaneous injection using 2x1 mL AI on Day 1 of the study. | 61 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Bimekizumab-AI-2mL (Test) | Bimekizumab-AI-2x1mL (Reference) | Total |
|---|---|---|---|
| Age, Continuous | 45.6 Years STANDARD_DEVIATION 11.7 | 44.8 Years STANDARD_DEVIATION 11.3 | 45.2 Years STANDARD_DEVIATION 11.5 |
| Age, Customized 18 - <65 yrs | 60 Participants | 59 Participants | 119 Participants |
| Age, Customized 65 - <85 yrs | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 6 Participants | 10 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 12 Participants | 12 Participants | 24 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 48 Participants | 49 Participants | 97 Participants |
| Race/Ethnicity, Customized Other or Mixed | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 50 Participants | 50 Participants | 100 Participants |
| Sex: Female, Male Female | 24 Participants | 24 Participants | 48 Participants |
| Sex: Female, Male Male | 36 Participants | 37 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 60 | 0 / 61 |
| other Total, other adverse events | 11 / 60 | 16 / 61 |
| serious Total, serious adverse events | 0 / 60 | 0 / 61 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC) for a Single Dose Bimekizumab (BKZ)
AUC is the area under the plasma concentration-time curve from time 0 (Day 1 predose) to infinity.
Time frame: Baseline (Day 1 predose) at predefined time points (up to Day 140)
Population: The Pharmacokinetic Set (PKS) was a subset of the SS, consisted of those study participants that received at least 1 total dose of IMP and had at least 1 observable pharmacokinetic measurement and who had no important protocol deviations affecting pharmacokinetics (PK) during the whole study phase. Number of participants analyzed included those participants who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Bimekizumab-AI-2mL (Test) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC) for a Single Dose Bimekizumab (BKZ) | 1223 days*micrograms/milliliter (days*ug/mL) |
| Bimekizumab-AI-2x1mL (Reference) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC) for a Single Dose Bimekizumab (BKZ) | 1255 days*micrograms/milliliter (days*ug/mL) |
90% CI: [90.2, 105.4]
Primary
Area Under the Plasma Concentration-time Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) for a Single Dose Bimekizumab (BKZ)
AUC0-t is the area under the plasma concentration-time curve from time zero (Day 1 predose) to the last quantifiable concentration.
Time frame: From Baseline (Day 1 predose) at predefined time points to the last quantifiable concentration (Day 140)
Population: The PKS was a subset of the SS, consisted of those study participants that received at least 1 total dose of IMP and had at least 1 observable pharmacokinetic measurement and who had no important protocol deviations affecting PK during the whole study phase. Number of participants analyzed included those participants who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Bimekizumab-AI-2mL (Test) | Area Under the Plasma Concentration-time Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) for a Single Dose Bimekizumab (BKZ) | 1186 day*ug/mL |
| Bimekizumab-AI-2x1mL (Reference) | Area Under the Plasma Concentration-time Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) for a Single Dose Bimekizumab (BKZ) | 1223 day*ug/mL |
90% CI: [90.1, 104.55]
Primary
Maximum Plasma Concentration (Cmax) for a Single Dose Bimekizumab (BKZ)
Cmax is a maximum observed plasma concentration.
Time frame: From Baseline (Day 1 predose) at predefined time points (up to Day 140)
Population: The PKS was a subset of the SS, consisted of those study participants that received at least 1 total dose of IMP and had at least 1 observable pharmacokinetic measurement and who had no important protocol deviations affecting PK during the whole study phase. Number of participants analyzed included those participants who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Bimekizumab-AI-2mL (Test) | Maximum Plasma Concentration (Cmax) for a Single Dose Bimekizumab (BKZ) | 35.17 micrograms/milliliter (ug/mL) |
| Bimekizumab-AI-2x1mL (Reference) | Maximum Plasma Concentration (Cmax) for a Single Dose Bimekizumab (BKZ) | 36.55 micrograms/milliliter (ug/mL) |
90% CI: [88.6, 104.47]
Secondary
Apparent Terminal Half-life (t1/2)
Apparent terminal half-life as determined via linear regression (slope=-lamdbaz) of the natural log (ln) concentration versus time, for data points in the terminal phase of the concentration time curve (ln2/lambdaz).
Time frame: From Baseline (Day 1 predose) at predefined time points (up to Day 140)
Population: The PKS was a subset of the SS, consisted of those study participants that received at least 1 total dose of IMP and had at least 1 observable pharmacokinetic measurement and who had no important protocol deviations affecting PK during the whole study phase. Number of participants analyzed included those participants who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Bimekizumab-AI-2mL (Test) | Apparent Terminal Half-life (t1/2) | 24.65 days |
| Bimekizumab-AI-2x1mL (Reference) | Apparent Terminal Half-life (t1/2) | 24.38 days |
90% CI: [94.18, 108.59]
Secondary
Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE) From Baseline to End of Safety Follow-Up
An AE is any untoward medical occurrence in a patient or clinical study participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAEs are defined as AEs not present prior to the administration of IMP or any unresolved event already present before administration of IMP that worsens in intensity following exposure to study treatment.
Time frame: From Baseline (Day 1) to end of Safety Follow-Up (up to Day 140)
Population: The SS consisted of all study participants who randomized and received full or partial IMP according to the treatment the study participants actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bimekizumab-AI-2mL (Test) | Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE) From Baseline to End of Safety Follow-Up | 43.3 percentage of participants |
| Bimekizumab-AI-2x1mL (Reference) | Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE) From Baseline to End of Safety Follow-Up | 49.2 percentage of participants |
Secondary
Percentage of Participants With at Least One Treatment-emergent Serious Adverse Event (SAE) From Baseline to End of Safety Follow-Up
A SAE is defined as any untoward medical occurrence that at any dose: a. Results in death, b. Is life-threatening, c. Requires inpatient hospitalization or prolongation of existing hospitalization, d. Results in persistent disability/incapacity, e. Is a congenital anomaly/ birth defect, f. Is an important medical event which based on appropriate medical judgment, jeopardized the study participant and required medical or surgical intervention to prevent any of the above.
Time frame: From Baseline (Day 1) to end of Safety Follow-Up (up to Day 140)
Population: The SS consisted of all study participants who randomized and received full or partial IMP according to the treatment the study participants actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bimekizumab-AI-2mL (Test) | Percentage of Participants With at Least One Treatment-emergent Serious Adverse Event (SAE) From Baseline to End of Safety Follow-Up | 0 percentage of participants |
| Bimekizumab-AI-2x1mL (Reference) | Percentage of Participants With at Least One Treatment-emergent Serious Adverse Event (SAE) From Baseline to End of Safety Follow-Up | 0 percentage of participants |
Secondary
Time of Occurrence of the Maximum Observed Concentration (Tmax) of a Single Dose Bimekizumab (BKZ)
tmax is the time to reach maximum plasma concentration.
Time frame: From Baseline (Day 1 predose) at predefined time points (up to Day 140)
Population: The PKS was a subset of the SS, consisted of those study participants that received at least 1 total dose of IMP and had at least 1 observable pharmacokinetic measurement and who had no important protocol deviations affecting PK during the whole study phase. Number of participants analyzed included those participants who were evaluable for the assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bimekizumab-AI-2mL (Test) | Time of Occurrence of the Maximum Observed Concentration (Tmax) of a Single Dose Bimekizumab (BKZ) | 6.962 day |
| Bimekizumab-AI-2x1mL (Reference) | Time of Occurrence of the Maximum Observed Concentration (Tmax) of a Single Dose Bimekizumab (BKZ) | 5.979 day |
90% CI: [-0.0073, 0.9567]