Clinical trial NCT01330953: A First Human Study of a Ferroportin Antibody
Official title: A Single-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY2928057 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Anemia
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2011-04-07
Enrollment: 32
Sex: ALL
Minimum age (years): 21
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Clinically Significant Adverse Effects
timeFrame: Baseline through Day 85
Secondary outcomes:
measure: Pharmacokinetics, Area Under the Curve (AUC)
timeFrame: 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
measure: Pharmacokinetics, Maximum Concentration (Cmax)
timeFrame: 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
measure: Pharmacokinetics, Time to Maximum Concentration (Tmax)
timeFrame: 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
measure: Pharmacokinetics, Systemic Clearance (CL)
timeFrame: 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
measure: Pharmacokinetics, Volume of Distribution (V)
timeFrame: 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
measure: Pharmacokinetics, Terminal Half-Life (t1/2)
timeFrame: 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
measure: Change From Baseline in Serum Iron
timeFrame: Baseline, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15 and 22
measure: Number of Participants Forming Antibody to LY2928057
timeFrame: Baseline through Day 85
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: 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.