A First Human Study of a Ferroportin Antibody

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: LY2928057

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Single intravenous placebo dose.	Drug: Placebo; Single intravenous placebo dose.
Experimental: 30 mg LY2928057 (Cohort 1); 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; Single intravenous dose.; Other Names: Ferroportin antibody
Experimental: 100 mg LY2928057 (Cohort 2); 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; Single intravenous dose.; Other Names: Ferroportin antibody
Experimental: 300 mg LY2928057 (Cohort 3); 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; Single intravenous dose.; Other Names: Ferroportin antibody
Experimental: 1000 mg LY2928057 (Cohort 4); 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; Single intravenous dose.; Other Names: Ferroportin antibody

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Sheetz M, Barrington P, Callies S, Berg PH, McColm J, Marbury T, Decker B, Dyas GL, Truhlar SME, Benschop R, Leung D, Berg J, Witcher DR. Targeting the hepcidin-ferroportin pathway in anaemia of chronic kidney disease. Br J Clin Pharmacol. 2019 May;85(5):935-948. doi: 10.1111/bcp.13877. Epub 2019 Mar 4.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: March 15, 2011
• First Submitted That Met QC Criteria: April 6, 2011
• First Posted (Estimate): April 7, 2011

Study Record Updates

• Last Update Posted (Actual): July 30, 2018
• Last Update Submitted That Met QC Criteria: October 21, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Anemia
• Other Study ID Numbers: 14151; I5M-FW-FABA (Other Identifier: Eli Lilly and Company)