Healthy Volunteers
Conditions
Keywords
Healthy Volunteers
Brief summary
The purpose of this study is to assess the bioequivalence pharmacokinetics, safety, tolerability and device deficiencies of zilucoplan (ZLP) in healthy adult participants
Interventions
DRUGZilucoplan
Participants will receive a single sc injection of zilucoplan in the pre-specified sequence.
Sponsors
UCB Biopharma SRL
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent. * Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. * Participants must be vaccinated with a quadrivalent vaccine and serogroup B vaccine against meningococcal infections (N. meningitidis) at least 2 weeks before the first administration of IMP if not previously vaccinated within 3 years prior to the start of IMP administration. Study participants who are not previously vaccinated may receive Menactra® (quadrivalent vaccine) and Bexsero® (serogroup B vaccine) during the Screening Period, 2 weeks prior to initiating IMP. * Body mass index (BMI) ≥18.5 to ≤30.0kg/m2 at the Screening Visit. * Male and/or female: * A male participant must agree to use contraception during the Treatment Period as detailed in Appendix 4 of the protocol and for at least 40 days (approximately 5 half lives) after the last dose of IMP and refrain from donating sperm during this period. * A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: * Not a female/woman of childbearing potential (WOCBP) OR * A WOCBP who agrees to follow the contraceptive guidance during the Treatment Period and for at least 40 days (approximately 5 half lives), corresponding to time needed to eliminate IMP after the last dose of IMP. * Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in the protocol.
Exclusion criteria
* Participant has a history of or current significant medical disorder, psychiatric disorder, or laboratory abnormality that in the opinion of the Investigator makes the study participant unsuitable for participation in the study, including any previous or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking IMP; or interfering with the interpretation of data. * Current or recent systemic infection within 2 weeks before the first administration of IMP or infection requiring intravenous antibiotics within 4 weeks before the first administration of IMP. * Current history of alcohol or drug use disorder, as defined in Diagnostic and Statistical Manual of Mental Disorders V, within the previous 6 months. * Participant has a known hypersensitivity to any components of the IMP or comparative drugs (and/or an investigational device) as stated in the protocol. * Intended use of over-the-counter or prescription medication, vitamins, herbal/traditional medicines (including St John's Wort) or dietary supplements (excluding medicines for external use), with the exception of those specified in the Protocol, within 2 weeks before the first administration of IMP. * Participant has used hepatic enzyme-inducing drugs (eg, glucocorticoids, phenobarbital, isoniazid, phenytoin, rifampicin) within 2 months before the first administration of IMP. * Participant has previously participated in this study or participant has previously been assigned to treatment in a study of the medication under investigation in this study. * Participant has participated in another study of an IMP (and/or an investigational device) within the previous 30 days or 5 half-lives (whichever is longer), or is currently participating in another study of an IMP (and/or an investigational device). * Participants with clinically relevant abnormalities in a standard 12-lead electrocardiogram (ECG) at the Screening Visit as judged by the Investigator. * Presence of hepatitis B surface antigen at the Screening Visit or within 3 months prior to dosing. * Positive hepatitis C antibody test result at the Screening Visit or within 3 months prior to starting IMP. NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled if a confirmatory negative hepatitis C ribonucleic acid (RNA) test is obtained. * Positive hepatitis C RNA test result at the Screening Visit or within 3 months prior to first dose of IMP. NOTE: Test is optional and participants with negative hepatitis C antibody test are not required to also undergo hepatitis C RNA testing. * Positive human immunodeficiency virus antibody test at the Screening Visit. * Positive syphilis test at the Screening Visit. * Positive throat swab for N. meningitidis at the Screening Visit or a prior history of meningitis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time Zero (Predose [Day 1]) to Infinity (AUC) for Zilucoplan | Baseline (Day 1 of each treatment period at predose) and at predefined time points up to 816 hours (Day 35) postdose | AUC was defined as the area under the plasma concentration-time curve from time zero (predose \[Day 1\]) to infinity for zilucoplan. |
| Area Under the Plasma Concentration-time Curve From Time 0 (Predose [Day 1]) to the Time of the Last Quantifiable Concentration (AUC[0-t]) for Zilucoplan | Baseline (Day 1 of each treatment period at predose) and at predefined time points up to 816 hours (Day 35) postdose | AUC(0-t) was defined as the area under the plasma concentration-time curve from time 0 (predose \[Day 1\]) to the time of the last quantifiable concentration for zilucoplan. |
| Maximum Observed Plasma Concentration (Cmax) for Zilucoplan | Baseline (Day 1 of each treatment period at predose) and at predefined time points up to 816 hours (Day 35) postdose | Cmax was defined as the maximum observed plasma concentration for zilucoplan. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) From Day 1 up to the End of Study (EOS) Visit or Early Termination (ET) Visit | From Day 1 to EOS visit or ET visit (up to 82 days) | An AE was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational medicinal product, whether or not considered related to the investigational medicinal product. A TEAE was defined as any AE with a start date/time on or after the administration of IMP in each Treatment Period, and up to and including 40 days after the single dose in each Treatment Period (or up to the first dose in Period 2 (for TEAEs following the first dose in Period 1) or last contact date (for TEAEs following the first dose in Period 2) depending on which occurs first. Percentages were displayed to one decimal place and was correspond to whole participant counts due to rounding. |
| Percentage of Participants With Non-serious Adverse Device Effects (ADE) From Day 1 up to the End of Study (EOS) Visit or Early Termination (ET) Visit | From Day 1 to EOS visit or ET visit (up to 82 days) | An AE was defined as any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory finding) in study participants, users, or other persons, whether or not related to the investigational medical device. An ADE was defined as an AE related to the use of an investigational medical device. |
| Percentage of Participants With Serious Treatment-emergent Adverse Events (Serious TEAEs) From Day 1 up to the End of Study (EOS) Visit or Early Termination (ET) Visit | From Day 1 to EOS visit or ET visit (up to 82 days) | An SAE was defined as any untoward medical occurrence that, at any dose, met 1 or more of the criteria listed: * Results in death * Is life-threatening * Requires inpatient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Is a congenital anomaly/birth defect * Important medical events such as (but not limited to) invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias, convulsions not resulting in hospitalization, or development of intervention dependency or intervention abuse. |
| Percentage of Participants With Serious Adverse Device Effects (SADE) From Day 1 up to the End of Study (EOS) Visit or Early Termination (ET) Visit | From Day 1 to EOS visit or ET visit (up to 82 days) | An SAE was defined as any untoward medical occurrence that, at any dose, met 1 or more of the criteria listed: * Results in death * Is life-threatening * Requires inpatient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Is a congenital anomaly/birth defect * Important medical events such as (but not limited to) invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias, convulsions not resulting in hospitalization, or development of intervention dependency or intervention abuse. A SADE was defined as an adverse device effect that has resulted in any of the consequences characteristic of a SAE. |
Countries
Netherlands
Participant flow
Recruitment details
The study started to enroll participants in August 2024 and concluded in November 2024.
Pre-assignment details
The Participant Flow refers to the All randomized Study Participants.
Participants by arm
| Arm | Count |
|---|---|
| Sequence: Treatment A (ZLP-PFS) - Treatment B (ZLP-AI) Participants received a single subcutaneous (sc) injection in abdomen using zilucoplan pre-filled syringe (ZLP-PFS) (Treatment A) on Day 1 of Period 1 and a single sc injection in abdomen using zilucoplan auto-injector (ZLP-AI) (Treatment B) on Day 1 of Period 2 in the treatment sequence A-B. Each treatment period was of 35 days and was separated by 7-Days Washout period. | 7 |
| Sequence: Treatment B (ZLP-AI) - Treatment A (ZLP-PFS) Participants received a single sc injection using ZLP-AI (Treatment B) on Day 1 of Period 1 and a single sc injection in abdomen using ZLP-PFS (Treatment A) on Day 1 of Period 2 in the treatment sequence B-A. Each treatment period was of 35 days and was separated by 7-Days Washout period. | 7 |
| Total | 14 |
Baseline characteristics
| Characteristic | Sequence: Treatment A (ZLP-PFS) - Treatment B (ZLP-AI) | Sequence: Treatment B (ZLP-AI) - Treatment A (ZLP-PFS) | Total |
|---|---|---|---|
| Age, Continuous | 29.0 years STANDARD_DEVIATION 5.9 | 36.1 years STANDARD_DEVIATION 15.9 | 30.8 years STANDARD_DEVIATION 10 |
| Age, Customized 18 - <65 years | 7 Participants | 7 Participants | 14 Participants |
| Age, Customized 65 - <85 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >=85 years | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 7 Participants | 7 Participants | 14 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other or Mixed | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 5 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 10 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 8 / 14 | 8 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve From Time 0 (Predose [Day 1]) to the Time of the Last Quantifiable Concentration (AUC[0-t]) for Zilucoplan
AUC(0-t) was defined as the area under the plasma concentration-time curve from time 0 (predose \[Day 1\]) to the time of the last quantifiable concentration for zilucoplan.
Time frame: Baseline (Day 1 of each treatment period at predose) and at predefined time points up to 816 hours (Day 35) postdose
Population: The PK Set consisted of all study participants who were randomized, received at least 1 dose of ZLP, and had at least 1 observable PK concentration measurement.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| ZLP-PFS | Area Under the Plasma Concentration-time Curve From Time 0 (Predose [Day 1]) to the Time of the Last Quantifiable Concentration (AUC[0-t]) for Zilucoplan | 921190 h*ng/mL | Geometric Coefficient of Variation 14.5 |
| ZLP-AI | Area Under the Plasma Concentration-time Curve From Time 0 (Predose [Day 1]) to the Time of the Last Quantifiable Concentration (AUC[0-t]) for Zilucoplan | 904500 h*ng/mL | Geometric Coefficient of Variation 16.4 |
90% CI: [0.9543, 1.0102]Mixed Effects model
Primary
Area Under the Plasma Concentration-time Curve From Time Zero (Predose [Day 1]) to Infinity (AUC) for Zilucoplan
AUC was defined as the area under the plasma concentration-time curve from time zero (predose \[Day 1\]) to infinity for zilucoplan.
Time frame: Baseline (Day 1 of each treatment period at predose) and at predefined time points up to 816 hours (Day 35) postdose
Population: The Pharmacokinetic (PK) Set consisted of all study participants who were randomized, received at least 1 dose of ZLP, and had at least 1 observable PK concentration measurement.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| ZLP-PFS | Area Under the Plasma Concentration-time Curve From Time Zero (Predose [Day 1]) to Infinity (AUC) for Zilucoplan | 950930 hour*nanogram per milliliters (h*ng/mL) | Geometric Coefficient of Variation 15 |
| ZLP-AI | Area Under the Plasma Concentration-time Curve From Time Zero (Predose [Day 1]) to Infinity (AUC) for Zilucoplan | 932740 hour*nanogram per milliliters (h*ng/mL) | Geometric Coefficient of Variation 17.1 |
90% CI: [0.9529, 1.0097]Mixed Effects model
Primary
Maximum Observed Plasma Concentration (Cmax) for Zilucoplan
Cmax was defined as the maximum observed plasma concentration for zilucoplan.
Time frame: Baseline (Day 1 of each treatment period at predose) and at predefined time points up to 816 hours (Day 35) postdose
Population: The PK Set consisted of all study participants who were randomized, received at least 1 dose of ZLP, and had at least 1 observable PK concentration measurement.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| ZLP-PFS | Maximum Observed Plasma Concentration (Cmax) for Zilucoplan | 5599.8 nanograms per milliliters (ng/mL) | Geometric Coefficient of Variation 11.3 |
| ZLP-AI | Maximum Observed Plasma Concentration (Cmax) for Zilucoplan | 5597.6 nanograms per milliliters (ng/mL) | Geometric Coefficient of Variation 11 |
90% CI: [0.9594, 1.0416]Mixed Effects model
Secondary
Percentage of Participants With Non-serious Adverse Device Effects (ADE) From Day 1 up to the End of Study (EOS) Visit or Early Termination (ET) Visit
An AE was defined as any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory finding) in study participants, users, or other persons, whether or not related to the investigational medical device. An ADE was defined as an AE related to the use of an investigational medical device.
Time frame: From Day 1 to EOS visit or ET visit (up to 82 days)
Population: The SS consisted of all study participants who were randomized and receive at least 1 dose of ZLP. Study participants were classified according to the sequence to which they were randomly assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZLP-PFS | Percentage of Participants With Non-serious Adverse Device Effects (ADE) From Day 1 up to the End of Study (EOS) Visit or Early Termination (ET) Visit | 0 percentage of participants |
| ZLP-AI | Percentage of Participants With Non-serious Adverse Device Effects (ADE) From Day 1 up to the End of Study (EOS) Visit or Early Termination (ET) Visit | 0 percentage of participants |
Secondary
Percentage of Participants With Serious Adverse Device Effects (SADE) From Day 1 up to the End of Study (EOS) Visit or Early Termination (ET) Visit
An SAE was defined as any untoward medical occurrence that, at any dose, met 1 or more of the criteria listed: * Results in death * Is life-threatening * Requires inpatient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Is a congenital anomaly/birth defect * Important medical events such as (but not limited to) invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias, convulsions not resulting in hospitalization, or development of intervention dependency or intervention abuse. A SADE was defined as an adverse device effect that has resulted in any of the consequences characteristic of a SAE.
Time frame: From Day 1 to EOS visit or ET visit (up to 82 days)
Population: The SS consisted of all study participants who were randomized and receive at least 1 dose of ZLP. Study participants were classified according to the sequence to which they were randomly assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZLP-PFS | Percentage of Participants With Serious Adverse Device Effects (SADE) From Day 1 up to the End of Study (EOS) Visit or Early Termination (ET) Visit | 0 percentage of participants |
| ZLP-AI | Percentage of Participants With Serious Adverse Device Effects (SADE) From Day 1 up to the End of Study (EOS) Visit or Early Termination (ET) Visit | 0 percentage of participants |
Secondary
Percentage of Participants With Serious Treatment-emergent Adverse Events (Serious TEAEs) From Day 1 up to the End of Study (EOS) Visit or Early Termination (ET) Visit
An SAE was defined as any untoward medical occurrence that, at any dose, met 1 or more of the criteria listed: * Results in death * Is life-threatening * Requires inpatient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Is a congenital anomaly/birth defect * Important medical events such as (but not limited to) invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias, convulsions not resulting in hospitalization, or development of intervention dependency or intervention abuse.
Time frame: From Day 1 to EOS visit or ET visit (up to 82 days)
Population: The SS consisted of all study participants who were randomized and receive at least 1 dose of ZLP. Study participants were classified according to the sequence to which they were randomly assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZLP-PFS | Percentage of Participants With Serious Treatment-emergent Adverse Events (Serious TEAEs) From Day 1 up to the End of Study (EOS) Visit or Early Termination (ET) Visit | 0 percentage of participants |
| ZLP-AI | Percentage of Participants With Serious Treatment-emergent Adverse Events (Serious TEAEs) From Day 1 up to the End of Study (EOS) Visit or Early Termination (ET) Visit | 0 percentage of participants |
Secondary
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) From Day 1 up to the End of Study (EOS) Visit or Early Termination (ET) Visit
An AE was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational medicinal product, whether or not considered related to the investigational medicinal product. A TEAE was defined as any AE with a start date/time on or after the administration of IMP in each Treatment Period, and up to and including 40 days after the single dose in each Treatment Period (or up to the first dose in Period 2 (for TEAEs following the first dose in Period 1) or last contact date (for TEAEs following the first dose in Period 2) depending on which occurs first. Percentages were displayed to one decimal place and was correspond to whole participant counts due to rounding.
Time frame: From Day 1 to EOS visit or ET visit (up to 82 days)
Population: The safety set (SS) consisted of all study participants who were randomized and receive at least 1 dose of ZLP. Study participants were classified according to the sequence to which they were randomly assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZLP-PFS | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) From Day 1 up to the End of Study (EOS) Visit or Early Termination (ET) Visit | 57.1 percentage of participants |
| ZLP-AI | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) From Day 1 up to the End of Study (EOS) Visit or Early Termination (ET) Visit | 57.1 percentage of participants |