Healthy
Conditions
Brief summary
The main purpose of this study is to evaluate the safety of the study drug known as mirikizumab. The study will investigate how the body processes the study drug. It will last up to about 4 months for each participant.
Interventions
DRUGMirikizumab - IV
Administered IV
DRUGMirikizumab - SC
Administered SC
DRUGPlacebo - IV
Administered IV
DRUGPlacebo - SC
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Native Chinese (all 4 biological grandparents and both biological parents to be Chinese origin) * Have a body mass index (BMI) of 18.0 to 32.0 kilograms per square meter (kg/m²), inclusive, at time of screening * Have clinical laboratory test results within normal reference range for the investigative site or results with acceptable deviations that are judged to be not clinically significant by the investigator * Have venous access sufficient to allow for blood sampling and administration of investigational product (IP) or placebo * Are reliable and willing to be available for the duration of the study and are willing to follow study procedures * Are able and willing to give signed informed consent
Exclusion criteria
* Are currently enrolled in a clinical study involving an IP or any other type of medical research judged not to be scientifically or medically compatible with this study * Have participated in a clinical trial involving an IP within 30 days or 5 half-lives (whichever is longer) prior to screening. If the clinical trial involved treatment with biologic agents (such as monoclonal antibodies, including marketed drugs), at least 3 months or 5 half-lives (whichever is longer) should have elapsed prior to Day 1 * Have known allergies to LY3074828, humanized monoclonal antibodies, related compounds or any components of the formulation, or history of significant atopy * Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies * Show evidence of hepatitis C and/or positive hepatitis C antibody * Show evidence of hepatitis B and/or positive hepatitis B surface antigen or positive hepatitis B core antibody * Have had symptomatic herpes zoster within 3 months of screening * Show evidence of active or latent tuberculosis (TB), as documented by medical history, examination, chest X-rays (posterior/anterior and lateral), and TB testing (positive or indeterminate for QuantiFERON® -TB Gold test or T-Spot. 1 retest permitted following indeterminate result); or have had household contact with a person with active TB, unless appropriate and documented prophylaxis treatment has been given. Participants with any history of active TB are excluded from the study, regardless of previous or current TB treatments. * Have received live vaccine(s), including attenuated live vaccines and those administered intranasally, within 8 weeks of screening, or intend to during the study * Are immunocompromised * Have clinically significant multiple or severe drug allergies, or intolerance to topical corticosteroids, or severe post treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A dermatosis, toxic epidermal necrolysis, or exfoliative dermatitis)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) | Baseline through Day 85 | Drug-related TEAEs are any untoward medical occurrence that either occurs or worsens at any time after treatment baseline, and in the opinion of the investigators is possibly related to study drug. A summary of serious adverse events (SAEs) and other non-serious adverse events (NSAEs), regardless of whether or not they were possibly related to study drug, is located in the Reported Adverse Event section. |
| Visual Analog Scale (VAS) Pain Score for Subcutaneous Injection Site | 0 min, 0.25 hours (h), 0.5 h, 1 h, 2 h and 4 h post first injection | The injection pain VAS score is a participant administered single item scale designed to measure pain using a 0-100 millimeter (mm) horizontal VAS. The severity of pain was categorized by VAS pain score as: no pain (0), mild pain ≤ 30, moderate pain (\>30 and ≤70), and severe pain (\>70). Overall severity of participant's pain is indicated by placing a single mark on the horizontal 100 mm scale from 0 mm (no pain) to 100 mm (worst imaginable pain). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Mirikizumab | Pre-dose, [end of infusion (EOI) IV only], Day 1: 6 hours (h), Day 2, Day 4, Day 8, Day 11 (SC only), Day 15, Day 22, Day 29, Day 43, Day 57, Day 71, and Day 85 postdose | PK: Cmax of Mirikizumab was evaluated. |
| PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of Mirikizumab | Pre-dose, [end of infusion (EOI) IV only], Day 1: 6 hours (h), Day 2, Day 4, Day 8, Day 11 (SC only), Day 15, Day 22, Day 29, Day 43, Day 57, Day 71, and Day 85 postdose | PK: AUC(0-∞) of Mirikizumab was evaluated. |
| PK: AUC From Time Zero to Time T, Where T is the Last Sample With a Measurable Concentration (AUC[0-tlast]) of Mirikizumab | Pre-dose, [end of infusion (EOI) IV only], Day 1: 6 hours (h), Day 2, Day 4, Day 8, Day 11 (SC only), Day 15, Day 22, Day 29, Day 43, Day 57, Day 71, and Day 85 postdose | PK: AUC(0-tlast) of Mirikizumab was evaluated. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo IV Participants received a single dose of placebo administered IV using a forearm vein. | 6 |
| 300 mg Mirikizumab IV Participants received a single dose of 300 mg mirikizumab administered IV using a forearm vein infused over at least 30 minutes. | 10 |
| 600 mg Mirikizumab IV Participants received a single dose of 600 mg mirikizumab administered IV using a forearm vein infused over at least 60 minutes. | 10 |
| 1200 mg Mirikizumab IV Participants received a single dose of 1200 mg mirikizumab administered IV using a forearm vein infused over at least 2 hours. | 10 |
| Placebo SC Participants received a single dose of placebo administered SC as 2 injections, 1 into the skinfold of each lower abdominal wall quadrant (left and right). | 4 |
| 200 mg Mirikizumab SC Participants received a single dose of 200 mg mirikizumab administered SC as 2 injections, 1 into the skinfold of each lower abdominal wall quadrant (left and right). | 10 |
| 400 mg Mirikizumab SC Participants received a single dose of 400 mg mirikizumab administered SC as 4 injections, 1 into the skinfold of each lower abdominal wall quadrant (left and right). | 10 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo IV | 300 mg Mirikizumab IV | 600 mg Mirikizumab IV | 1200 mg Mirikizumab IV | Placebo SC | 200 mg Mirikizumab SC | 400 mg Mirikizumab SC | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 26.0 years STANDARD_DEVIATION 6.2 | 32.4 years STANDARD_DEVIATION 6.4 | 31.7 years STANDARD_DEVIATION 5.3 | 36.5 years STANDARD_DEVIATION 6.1 | 25.0 years STANDARD_DEVIATION 5 | 33.9 years STANDARD_DEVIATION 7.2 | 31.8 years STANDARD_DEVIATION 6.2 | 32.0 years STANDARD_DEVIATION 6.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 10 Participants | 10 Participants | 10 Participants | 4 Participants | 10 Participants | 10 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 10 Participants | 10 Participants | 10 Participants | 4 Participants | 10 Participants | 10 Participants | 60 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 6 Participants | 10 Participants | 10 Participants | 10 Participants | 4 Participants | 10 Participants | 10 Participants | 60 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 4 Participants | 4 Participants | 0 Participants | 5 Participants | 4 Participants | 23 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 6 Participants | 6 Participants | 4 Participants | 5 Participants | 6 Participants | 37 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 | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 4 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 5 / 6 | 7 / 10 | 9 / 10 | 3 / 10 | 3 / 4 | 4 / 10 | 5 / 10 |
| serious Total, serious adverse events | 0 / 6 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 4 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs)
Drug-related TEAEs are any untoward medical occurrence that either occurs or worsens at any time after treatment baseline, and in the opinion of the investigators is possibly related to study drug. A summary of serious adverse events (SAEs) and other non-serious adverse events (NSAEs), regardless of whether or not they were possibly related to study drug, is located in the Reported Adverse Event section.
Time frame: Baseline through Day 85
Population: All randomized participants who received at least one dose of study drug and have at least one postdose safety assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo IV | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) | 1 participants |
| 300 mg Mirikizumab IV | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) | 3 participants |
| 600 mg Mirikizumab IV | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) | 4 participants |
| 1200 mg Mirikizumab IV | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) | 1 participants |
| Placebo SC | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) | 1 participants |
| 200 mg Mirikizumab SC | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) | 0 participants |
| 400 mg Mirikizumab SC | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) | 0 participants |
Primary
Visual Analog Scale (VAS) Pain Score for Subcutaneous Injection Site
The injection pain VAS score is a participant administered single item scale designed to measure pain using a 0-100 millimeter (mm) horizontal VAS. The severity of pain was categorized by VAS pain score as: no pain (0), mild pain ≤ 30, moderate pain (\>30 and ≤70), and severe pain (\>70). Overall severity of participant's pain is indicated by placing a single mark on the horizontal 100 mm scale from 0 mm (no pain) to 100 mm (worst imaginable pain).
Time frame: 0 min, 0.25 hours (h), 0.5 h, 1 h, 2 h and 4 h post first injection
Population: All randomized participants who received at least one dose of study drug and have at least one postdose safety assessment. As per statistical analysis plan, VAS pain score was analyzed only for SC dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo IV | Visual Analog Scale (VAS) Pain Score for Subcutaneous Injection Site | 0 min | 36.5 millimeter (mm) | Standard Deviation 36.3 |
| Placebo IV | Visual Analog Scale (VAS) Pain Score for Subcutaneous Injection Site | 0.25 h | 3.5 millimeter (mm) | Standard Deviation 3.3 |
| Placebo IV | Visual Analog Scale (VAS) Pain Score for Subcutaneous Injection Site | 0.5 h | 2.3 millimeter (mm) | Standard Deviation 2.6 |
| Placebo IV | Visual Analog Scale (VAS) Pain Score for Subcutaneous Injection Site | 1 h | 1.0 millimeter (mm) | Standard Deviation 0.8 |
| Placebo IV | Visual Analog Scale (VAS) Pain Score for Subcutaneous Injection Site | 2 h | 1.8 millimeter (mm) | Standard Deviation 1 |
| Placebo IV | Visual Analog Scale (VAS) Pain Score for Subcutaneous Injection Site | 4 h | 1.0 millimeter (mm) | Standard Deviation 0.8 |
| 300 mg Mirikizumab IV | Visual Analog Scale (VAS) Pain Score for Subcutaneous Injection Site | 4 h | 1.0 millimeter (mm) | Standard Deviation 1.2 |
| 300 mg Mirikizumab IV | Visual Analog Scale (VAS) Pain Score for Subcutaneous Injection Site | 0 min | 30.8 millimeter (mm) | Standard Deviation 29.5 |
| 300 mg Mirikizumab IV | Visual Analog Scale (VAS) Pain Score for Subcutaneous Injection Site | 1 h | 1.6 millimeter (mm) | Standard Deviation 1.9 |
| 300 mg Mirikizumab IV | Visual Analog Scale (VAS) Pain Score for Subcutaneous Injection Site | 2 h | 1.2 millimeter (mm) | Standard Deviation 1.5 |
| 300 mg Mirikizumab IV | Visual Analog Scale (VAS) Pain Score for Subcutaneous Injection Site | 0.25 h | 2.9 millimeter (mm) | Standard Deviation 3.7 |
| 300 mg Mirikizumab IV | Visual Analog Scale (VAS) Pain Score for Subcutaneous Injection Site | 0.5 h | 1.9 millimeter (mm) | Standard Deviation 3.4 |
| 600 mg Mirikizumab IV | Visual Analog Scale (VAS) Pain Score for Subcutaneous Injection Site | 0.25 h | 10.6 millimeter (mm) | Standard Deviation 20.2 |
| 600 mg Mirikizumab IV | Visual Analog Scale (VAS) Pain Score for Subcutaneous Injection Site | 0.5 h | 9.5 millimeter (mm) | Standard Deviation 23.1 |
| 600 mg Mirikizumab IV | Visual Analog Scale (VAS) Pain Score for Subcutaneous Injection Site | 4 h | 2.1 millimeter (mm) | Standard Deviation 2.6 |
| 600 mg Mirikizumab IV | Visual Analog Scale (VAS) Pain Score for Subcutaneous Injection Site | 1 h | 2.0 millimeter (mm) | Standard Deviation 1.8 |
| 600 mg Mirikizumab IV | Visual Analog Scale (VAS) Pain Score for Subcutaneous Injection Site | 0 min | 42.4 millimeter (mm) | Standard Deviation 26 |
| 600 mg Mirikizumab IV | Visual Analog Scale (VAS) Pain Score for Subcutaneous Injection Site | 2 h | 2.0 millimeter (mm) | Standard Deviation 2 |
Secondary
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Mirikizumab
PK: Cmax of Mirikizumab was evaluated.
Time frame: Pre-dose, [end of infusion (EOI) IV only], Day 1: 6 hours (h), Day 2, Day 4, Day 8, Day 11 (SC only), Day 15, Day 22, Day 29, Day 43, Day 57, Day 71, and Day 85 postdose
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Mirikizumab | 145 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 7 |
| 300 mg Mirikizumab IV | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Mirikizumab | 266 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 16 |
| 600 mg Mirikizumab IV | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Mirikizumab | 511 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 10 |
| 1200 mg Mirikizumab IV | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Mirikizumab | 14.9 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 28 |
| Placebo SC | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Mirikizumab | 23.1 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 44 |
Secondary
PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of Mirikizumab
PK: AUC(0-∞) of Mirikizumab was evaluated.
Time frame: Pre-dose, [end of infusion (EOI) IV only], Day 1: 6 hours (h), Day 2, Day 4, Day 8, Day 11 (SC only), Day 15, Day 22, Day 29, Day 43, Day 57, Day 71, and Day 85 postdose
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV | PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of Mirikizumab | 936 microgram*day per milliliter (μg*day/mL) | Geometric Coefficient of Variation 12 |
| 300 mg Mirikizumab IV | PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of Mirikizumab | 2030 microgram*day per milliliter (μg*day/mL) | Geometric Coefficient of Variation 12 |
| 600 mg Mirikizumab IV | PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of Mirikizumab | 3320 microgram*day per milliliter (μg*day/mL) | Geometric Coefficient of Variation 23 |
| 1200 mg Mirikizumab IV | PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of Mirikizumab | 263 microgram*day per milliliter (μg*day/mL) | Geometric Coefficient of Variation 29 |
| Placebo SC | PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of Mirikizumab | 421 microgram*day per milliliter (μg*day/mL) | Geometric Coefficient of Variation 46 |
Secondary
PK: AUC From Time Zero to Time T, Where T is the Last Sample With a Measurable Concentration (AUC[0-tlast]) of Mirikizumab
PK: AUC(0-tlast) of Mirikizumab was evaluated.
Time frame: Pre-dose, [end of infusion (EOI) IV only], Day 1: 6 hours (h), Day 2, Day 4, Day 8, Day 11 (SC only), Day 15, Day 22, Day 29, Day 43, Day 57, Day 71, and Day 85 postdose
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV | PK: AUC From Time Zero to Time T, Where T is the Last Sample With a Measurable Concentration (AUC[0-tlast]) of Mirikizumab | 964 μg*day/mL | Geometric Coefficient of Variation 15 |
| 300 mg Mirikizumab IV | PK: AUC From Time Zero to Time T, Where T is the Last Sample With a Measurable Concentration (AUC[0-tlast]) of Mirikizumab | 2010 μg*day/mL | Geometric Coefficient of Variation 12 |
| 600 mg Mirikizumab IV | PK: AUC From Time Zero to Time T, Where T is the Last Sample With a Measurable Concentration (AUC[0-tlast]) of Mirikizumab | 3300 μg*day/mL | Geometric Coefficient of Variation 24 |
| 1200 mg Mirikizumab IV | PK: AUC From Time Zero to Time T, Where T is the Last Sample With a Measurable Concentration (AUC[0-tlast]) of Mirikizumab | 248 μg*day/mL | Geometric Coefficient of Variation 34 |
| Placebo SC | PK: AUC From Time Zero to Time T, Where T is the Last Sample With a Measurable Concentration (AUC[0-tlast]) of Mirikizumab | 417 μg*day/mL | Geometric Coefficient of Variation 46 |