Healthy Study Participants
Conditions
Keywords
UCB4940, Bimekizumab, Bioequivalence, Auto-injector, Healthy study participants, Safety-syringe
Brief summary
The purpose of the study is to compare the pharmacokinetics (PK) of bimekizumab when administered subcutaneously (sc) as 1x2 mL versus 2x1 mL, using a bimekizumab-safety syringe presentation or bimekizumab-auto-injector presentation, in healthy study participants.
Interventions
DRUGBimekizumab
Study participants will receive a single-dose of bimekizumab 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 Visit 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
Exclusion criteria
* Study participant has any medical or psychiatric condition that, in the opinion of the Investigator, could jeopardize or would compromise the study participant's ability to participate in this study * Study participant has a known hypersensitivity to any excipients of bimekizumab (and/or an investigational device) as stated in this protocol * Study participant has cardiovascular or cerebrovascular disease, including hypertension, angina, ischemic heart disease, transient ischemic attacks, stroke, peripheral arterial disease sufficient to cause symptoms, and/or requires therapy to maintain stable status * Study participant has an active infection or history of infections as follows: 1. Any active infection (except common cold) within 14 days prior to the Screening Visit 2. A serious infection, defined as requiring hospitalization or iv anti-infectives within 2 months prior to the Screening Visit 3. 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 tuberculosis (TB) test or evidence of possible TB or latent TB infection at the Screening Visit * Study participant has concurrent acute or chronic viral hepatitis B or C or human immunodeficiency virus (HIV) infection. Study participants who have evidence of, or tested positive for hepatitis B or hepatitis C are excluded * Study participant has 12-lead ECG with changes considered to be clinically significant (eg, QT interval corrected using Fridericia's formula \[QTcF\] \>450 ms, bundle branch block, or evidence of myocardial ischemia) at the Screening Visit or on Day -1 * Study participant has active neoplastic disease or history of neoplastic disease within 5 years of the Screening Visit (except for basal or squamous cell carcinoma of the skin or carcinoma in situ that has been definitively treated with standard of care) * Study participants receiving any live (includes attenuated) vaccination within the 8 weeks prior to the Screening Visit (eg, inactivated influenza and pneumococcal vaccines are allowed but nasal influenza vaccination is not permitted). Live vaccines are not allowed during the study or for 20 weeks after the dose of the investigational medicinal product (IMP) * Study participant has previously participated in this study or the study participant has previously been assigned to treatment in a study of the medication under investigation in this study * Study participant has participated in another study of an IMP (and/or an investigational device) within the previous 90 days or 5 half-lives, whichever is longer, prior to IMP administration * Study participant has made a blood donation of a blood loss of more than 400 mL of blood or blood products within 90 days prior to admission (Day -1) or plans to donate blood during the study * Study participant has a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in real-time reverse transcriptase polymerase chain reaction (RT-PCR) on the admission sample * Study participant has clinical signs and symptoms consistent with coronavirus disease 2019 (COVID-19), eg fever, dry cough, dyspnea, sore throat, fatigue, or confirmed infection by appropriate laboratory test within the previous 14 days prior to Screening or on admission * Study participant who had severe course of COVID-19 (ie, hospitalization, extracorporal membrane oxygenation, mechanically ventilated)
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) | From Baseline (Day 1 predose) at predefined time points (up to Day 140) | AUC is the area under the bimekizumab plasma concentration-time curve from time zero (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 bimekizumab plasma concentration-time curve from time zero (Day 1 predose) to the last observed 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 the 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 adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject 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. Treatment-emergent adverse events (TEAEs) were defined as any event 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 serious adverse event (SAE) was 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. Other important medical events 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, reported in units of days, as determined via simple linear regression (slope=-lambdaz) of natural log (ln) concentration versus time for data points in the terminal phase of the concentration-time curve. t1/2 is calculated as ln2/lambdaz. |
Countries
Germany
Participant flow
Recruitment details
The study started to enroll study participants in February 2020 and concluded in April 2021.
Pre-assignment details
Participant Flow refers to the Randomized Set (RS) which consisted of all randomized study participants.
Participants by arm
| Arm | Count |
|---|---|
| Bimekizumab-SS-2mL (Test 1) Participants randomized to this arm received a single dose of bimekizumab 320 milligrams (mg) administered as a subcutaneous injection using a 2 milliliter (mL) safety syringe (SS) on Day 1 of the study. | 18 |
| Bimekizumab-SS-2x1mL (Reference 1) Participants randomized to this arm received a single dose of bimekizumab 320 mg (2x160 mg) administered as a subcutaneous injection using 2x1 mL SS on Day 1 of the study. | 18 |
| Bimekizumab-AI-2mL (Test 2) Participants randomized to this arm received a single dose of bimekizumab 320 mg administered as a subcutaneous injection using a 2 mL auto-injector (AI) on Day 1 of the study. | 17 |
| Bimekizumab-AI-2x1mL (Reference 2) Participants randomized to this arm 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. | 18 |
| Total | 71 |
Baseline characteristics
| Characteristic | Bimekizumab-AI-2x1mL (Reference 2) | Total | Bimekizumab-SS-2mL (Test 1) | Bimekizumab-SS-2x1mL (Reference 1) | Bimekizumab-AI-2mL (Test 2) |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 5 Participants | 1 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 66 Participants | 17 Participants | 17 Participants | 16 Participants |
| Age, Continuous | 46.7 years STANDARD_DEVIATION 15.7 | 49.3 years STANDARD_DEVIATION 15 | 52.6 years STANDARD_DEVIATION 12.8 | 51.1 years STANDARD_DEVIATION 15.8 | 46.8 years STANDARD_DEVIATION 15.7 |
| Race/Ethnicity, Customized Not Hispanic or Latino | 18 Participants | 71 Participants | 18 Participants | 18 Participants | 17 Participants |
| Race/Ethnicity, Customized Other/Black | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Other/Caucasian | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 18 Participants | 69 Participants | 17 Participants | 17 Participants | 17 Participants |
| Sex: Female, Male Female | 13 Participants | 51 Participants | 12 Participants | 13 Participants | 13 Participants |
| Sex: Female, Male Male | 5 Participants | 20 Participants | 6 Participants | 5 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 | 0 / 17 | 0 / 18 |
| other Total, other adverse events | 12 / 18 | 8 / 18 | 12 / 17 | 7 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 17 | 0 / 18 |
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 bimekizumab plasma concentration-time curve from time zero (Day 1 predose) to infinity.
Time frame: From Baseline (Day 1 predose) at predefined time points (up to Day 140)
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK variables and for whom a sufficient number of samples were available to determine at least 1 PK parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Bimekizumab-SS-2mL (Test 1) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC) for a Single Dose Bimekizumab (BKZ) | 1665 days*micrograms/milliliter (days*ug/mL) | Geometric Coefficient of Variation 34.2 |
| Bimekizumab-SS-2x1mL (Reference 1) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC) for a Single Dose Bimekizumab (BKZ) | 1610 days*micrograms/milliliter (days*ug/mL) | Geometric Coefficient of Variation 31.3 |
| Bimekizumab-AI-2mL (Test 2) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC) for a Single Dose Bimekizumab (BKZ) | 1560 days*micrograms/milliliter (days*ug/mL) | Geometric Coefficient of Variation 19.1 |
| Bimekizumab-AI-2x1mL (Reference 2) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC) for a Single Dose Bimekizumab (BKZ) | 1357 days*micrograms/milliliter (days*ug/mL) | Geometric Coefficient of Variation 35.5 |
90% CI: [86.4, 123.8]
90% CI: [97.9, 135]
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 bimekizumab plasma concentration-time curve from time zero (Day 1 predose) to the last observed quantifiable concentration.
Time frame: From Baseline (Day 1 predose) at predefined time points to the last quantifiable concentration (Day 140)
Population: The PK-PPS was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK variables and for whom a sufficient number of samples were available to determine at least 1 PK parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Bimekizumab-SS-2mL (Test 1) | Area Under the Plasma Concentration-time Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) for a Single Dose Bimekizumab (BKZ) | 1551 days*ug/mL | Geometric Coefficient of Variation 31.4 |
| Bimekizumab-SS-2x1mL (Reference 1) | Area Under the Plasma Concentration-time Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) for a Single Dose Bimekizumab (BKZ) | 1509 days*ug/mL | Geometric Coefficient of Variation 29.2 |
| Bimekizumab-AI-2mL (Test 2) | Area Under the Plasma Concentration-time Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) for a Single Dose Bimekizumab (BKZ) | 1469 days*ug/mL | Geometric Coefficient of Variation 17.5 |
| Bimekizumab-AI-2x1mL (Reference 2) | Area Under the Plasma Concentration-time Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) for a Single Dose Bimekizumab (BKZ) | 1296 days*ug/mL | Geometric Coefficient of Variation 33.7 |
90% CI: [87, 121.5]
90% CI: [97.4, 131.9]
Primary
Maximum Plasma Concentration (Cmax) for a Single Dose Bimekizumab (BKZ)
Cmax is the maximum observed plasma concentration.
Time frame: From Baseline (Day 1 predose) at predefined time points (up to Day 140)
Population: The PK-PPS was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK variables and for whom a sufficient number of samples were available to determine at least 1 PK parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Bimekizumab-SS-2mL (Test 1) | Maximum Plasma Concentration (Cmax) for a Single Dose Bimekizumab (BKZ) | 43.56 ug/mL | Geometric Coefficient of Variation 26.8 |
| Bimekizumab-SS-2x1mL (Reference 1) | Maximum Plasma Concentration (Cmax) for a Single Dose Bimekizumab (BKZ) | 41.90 ug/mL | Geometric Coefficient of Variation 23.9 |
| Bimekizumab-AI-2mL (Test 2) | Maximum Plasma Concentration (Cmax) for a Single Dose Bimekizumab (BKZ) | 42.23 ug/mL | Geometric Coefficient of Variation 20.3 |
| Bimekizumab-AI-2x1mL (Reference 2) | Maximum Plasma Concentration (Cmax) for a Single Dose Bimekizumab (BKZ) | 36.94 ug/mL | Geometric Coefficient of Variation 28.2 |
90% CI: [90.3, 119.7]
90% CI: [99.5, 131.4]
Secondary
Apparent Terminal Half-life (t1/2)
Apparent terminal half-life, reported in units of days, as determined via simple linear regression (slope=-lambdaz) of natural log (ln) concentration versus time for data points in the terminal phase of the concentration-time curve. t1/2 is calculated as ln2/lambdaz.
Time frame: From Baseline (Day 1 predose) at predefined time points (up to Day 140)
Population: The PK-PPS was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK variables and for whom a sufficient number of samples were available to determine at least 1 PK parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Bimekizumab-SS-2mL (Test 1) | Apparent Terminal Half-life (t1/2) | 28.21 days | Geometric Coefficient of Variation 17.3 |
| Bimekizumab-SS-2x1mL (Reference 1) | Apparent Terminal Half-life (t1/2) | 27.24 days | Geometric Coefficient of Variation 16.8 |
| Bimekizumab-AI-2mL (Test 2) | Apparent Terminal Half-life (t1/2) | 25.73 days | Geometric Coefficient of Variation 27.8 |
| Bimekizumab-AI-2x1mL (Reference 2) | Apparent Terminal Half-life (t1/2) | 22.84 days | Geometric Coefficient of Variation 28.7 |
Secondary
Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE) From Baseline to End of Safety Follow-Up
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject 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. Treatment-emergent adverse events (TEAEs) were defined as any event 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 FAS consisted of all randomized study participants who received full or partial IMP according to the treatment the study participants actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bimekizumab-SS-2mL (Test 1) | Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE) From Baseline to End of Safety Follow-Up | 66.7 percentage of participants |
| Bimekizumab-SS-2x1mL (Reference 1) | Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE) From Baseline to End of Safety Follow-Up | 44.4 percentage of participants |
| Bimekizumab-AI-2mL (Test 2) | Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE) From Baseline to End of Safety Follow-Up | 70.6 percentage of participants |
| Bimekizumab-AI-2x1mL (Reference 2) | Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE) From Baseline to End of Safety Follow-Up | 38.9 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 serious adverse event (SAE) was 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. Other important medical events 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 FAS consisted of all randomized study participants who received full or partial IMP according to the treatment the study participants actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bimekizumab-SS-2mL (Test 1) | 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-SS-2x1mL (Reference 1) | 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-2mL (Test 2) | 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 2) | 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 PK-PPS was a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK variables and for whom a sufficient number of samples were available to determine at least 1 PK parameter.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bimekizumab-SS-2mL (Test 1) | Time of Occurrence of the Maximum Observed Concentration (Tmax) of a Single Dose Bimekizumab (BKZ) | 6.981 days |
| Bimekizumab-SS-2x1mL (Reference 1) | Time of Occurrence of the Maximum Observed Concentration (Tmax) of a Single Dose Bimekizumab (BKZ) | 6.988 days |
| Bimekizumab-AI-2mL (Test 2) | Time of Occurrence of the Maximum Observed Concentration (Tmax) of a Single Dose Bimekizumab (BKZ) | 6.943 days |
| Bimekizumab-AI-2x1mL (Reference 2) | Time of Occurrence of the Maximum Observed Concentration (Tmax) of a Single Dose Bimekizumab (BKZ) | 6.972 days |