A First Human Study of a Ferroportin Antibody

Study Overview
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Brief Summary
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The purposes of this study are to evaluate the following in healthy participants: 1) LY2928057 safety, including any side effects possibly associated with LY2928057; 2) how the body processes LY2928057; 3) effect of LY2928057 on blood iron levels; and 4) immune system reactions to LY2928057.

Official Title
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A Single-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY2928057 in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Placebo
* Drug: LY2928057


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must either be a healthy male (and willing to use reliable birth control method during the study and for 3 months following last study drug dose), or a healthy female who cannot become pregnant Must have a body mass index (BMI) between 18.5 and 32.0 kilograms per square meter (kg/m^2), inclusive, and a minimum body weight of 55 kg Must have acceptable blood and urine laboratory test results for the study Must have suitable veins suitable for easy blood collection and study drug administration Must be reliable, follow study procedures, and willing to be available for the duration of the study Must have given written informed consent Must have acceptable blood pressure and pulse rate for the study Exclusion Criteria: Blood test shows that participant has anemia due to lack of iron Currently participating in another clinical study or has completed one less than 30 days ago Allergic to biologic agents Have previously taken part in this study Have abnormal electrocardiogram (ECG) findings that suggest an increased risk with study participation Have a history of significant disease that may affect drug actions or pose risk when taking study medication Have a history of drug or alcohol abuse Are infected with human immunodeficiency virus (HIV) Have hepatitis B Are pregnant or breastfeeding Intend to use over-the-counter or prescription medication within 14 days before dosing, other than oestrogen/progesterone as hormone replacement therapy (HRT). Participants taking these medications are expected to be on chronic, stable doses. Certain medications (for example, vitamin supplements) may be permitted at the discretion of the investigator. Have donated more than 450 milliliter (mL) of blood within the last 3 months Have a regular alcohol intake greater than 21 units per week (male), or 14 units per week (female), or are unwilling to stop alcohol as required for the study (1 unit = 360 mL of beer, 150 mL of wine, or 45 mL of spirits) Are a smoker (smoking more than 10 cigarettes per day) or have used equivalent tobacco products. Participants will not be allowed to smoke while in the study unit. Have received live vaccine(s) within 1 month of screening, or intend to during the study Have received treatment with biologic agents (such as monoclonal antibodies) within 3 months or 5 half-lives (whichever is longer) before receiving study drug in this study Have a history of atopy, significant allergies to humanized monoclonal antibodies, clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A [IgA] dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis) Have any active mental health illness Study doctor does not feel the participant should be in the study for any reason

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Single intravenous placebo dose. | Drug: Placebo<br>* Single intravenous placebo dose.<br>|
| Experimental: 30 mg LY2928057 (Cohort 1)<br>Day 1: single 30-milligram (mg) LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 30-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 30-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 30 mg LY2928057. | Drug: LY2928057<br>* Single intravenous dose.<br>* Other names: Ferroportin antibody;|
| Experimental: 100 mg LY2928057 (Cohort 2)<br>Day 1: single 100-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 100-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 100-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 100 mg LY2928057. | Drug: LY2928057<br>* Single intravenous dose.<br>* Other names: Ferroportin antibody;|
| Experimental: 300 mg LY2928057 (Cohort 3)<br>Day 1: single 300-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 300-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 300-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 300 mg LY2928057. | Drug: LY2928057<br>* Single intravenous dose.<br>* Other names: Ferroportin antibody;|
| Experimental: 1000 mg LY2928057 (Cohort 4)<br>Day 1: single 1000-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 1000-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 1000-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 1000 mg LY2928057. | Drug: LY2928057<br>* Single intravenous dose.<br>* Other names: Ferroportin antibody;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinically Significant Adverse Effects | A clinically significant effect/event was defined as an adverse event (AE). A listing of serious and non-serious AEs is located in the Reported Adverse Event Module. | Baseline through Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics, Area Under the Curve (AUC) | Area under the LY2928057 plasma concentration-time curve extrapolated to infinite time (AUC0-∞). | Predose, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15, 22, 29, 43, 50, 57, 64, 71, and 85 | 
| Pharmacokinetics, Maximum Concentration (Cmax) |  | Predose, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15, 22, 29, 43, 50, 57, 64, 71, and 85 | 
| Pharmacokinetics, Time to Maximum Concentration (Tmax) |  | Predose, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15, 22, 29, 43, 50, 57, 64, 71, and 85 | 
| Pharmacokinetics, Systemic Clearance (CL) | CL=total body clearance of LY2928057 calculated after intravenous administration. Systemic CL was derived from LY2928057 serum concentration data following intravenous administration using classical non compartmental analysis (WinNonlin version 5.3). | Predose, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15, 22, 29, 43, 50, 57, 64, 71, and 85 | 
| Pharmacokinetics, Volume of Distribution (V) | V=LY2928057 steady-state volume of distribution (Vss) | Predose, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15, 22, 29, 43, 50, 57, 64, 71, and 85 | 
| Pharmacokinetics, Terminal Half-Life (t1/2) |  | Predose, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15, 22, 29, 43, 50, 57, 64, 71, and 85 | 
| Change From Baseline in Serum Iron | Maximum change from baseline to any point over 22 days post-infusion. | Baseline, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15 and 22 | 
| Number of Participants Forming Antibody to LY2928057 |  | Baseline through Day 85 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anemia