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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01330953

Enrollment

Registered

2011-04-07

Start date

2011-03-31

Completion date

2011-09-30

Last updated

2018-07-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy Volunteers

Keywords

Anemia

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.

Interventions

DRUGPlacebo

Single intravenous placebo dose.

DRUGLY2928057

Single intravenous dose.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

SINGLE (Subject)

Eligibility

Sex/Gender

ALL

Age

21 Years to 60 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Clinically Significant Adverse Effects	Baseline through Day 85	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.

Secondary

Measure	Time frame	Description
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)	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	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).
Pharmacokinetics, Area Under the Curve (AUC)	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	Area under the LY2928057 plasma concentration-time curve extrapolated to infinite time (AUC0-∞).
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	Baseline, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15 and 22	Maximum change from baseline to any point over 22 days post-infusion.
Number of Participants Forming Antibody to LY2928057	Baseline through Day 85	—
Pharmacokinetics, Volume of Distribution (V)	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	V=LY2928057 steady-state volume of distribution (Vss)

Countries

Singapore

Participant flow

Participants by arm

Arm	Count
Placebo Single intravenous placebo dose.	8
30 mg LY2928057 Day 1: single 30-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.	6
100 mg LY2928057 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.	6
300 mg LY2928057 Day 1: single 300-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: 1 participant receives 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.	6
1000 mg LY2928057 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.	6
Total	32

Baseline characteristics

Characteristic	Placebo	30 mg LY2928057	100 mg LY2928057	300 mg LY2928057	1000 mg LY2928057	Total
Age, Continuous	36.0 years STANDARD_DEVIATION 13.8	33.5 years STANDARD_DEVIATION 14.8	31.0 years STANDARD_DEVIATION 6.3	40.2 years STANDARD_DEVIATION 11.7	27.0 years STANDARD_DEVIATION 6.1	33.7 years STANDARD_DEVIATION 11.5
Race/Ethnicity, Customized Asian	8 participants	6 participants	6 participants	6 participants	6 participants	32 participants
Region of Enrollment Singapore	8 Participants	6 Participants	6 Participants	6 Participants	6 Participants	32 Participants
Sex: Female, Male Female	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Sex: Female, Male Male	7 Participants	6 Participants	6 Participants	6 Participants	6 Participants	31 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
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	7 / 8	6 / 6	5 / 6	5 / 6	6 / 6
serious Total, serious adverse events	0 / 8	0 / 6	0 / 6	0 / 6	0 / 6

Outcome results

Primary

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.

Time frame: Baseline through Day 85

Population: The analysis population included all randomized participants dosed with placebo or LY2928057, and who provided safety data at least up to and including the Day 8 assessment.

Arm	Measure	Value (NUMBER)
Placebo	Number of Participants With Clinically Significant Adverse Effects	7 participants
30 mg LY2928057	Number of Participants With Clinically Significant Adverse Effects	6 participants
100 mg LY2928057	Number of Participants With Clinically Significant Adverse Effects	5 participants
300 mg LY2928057	Number of Participants With Clinically Significant Adverse Effects	5 participants
1000 mg LY2928057	Number of Participants With Clinically Significant Adverse Effects	6 participants

Secondary

Change From Baseline in Serum Iron

Maximum change from baseline to any point over 22 days post-infusion.

Time frame: Baseline, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15 and 22

Population: The analysis population included all randomized participants who received at least 1 dose of LY2928057 and provided plasma data for measuring serum iron levels as the primary pharmacodynamic analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Change From Baseline in Serum Iron	32.9 microgram per deciliter (µg/dL)	Standard Deviation 17.5
30 mg LY2928057	Change From Baseline in Serum Iron	71.9 microgram per deciliter (µg/dL)	Standard Deviation 36.1
100 mg LY2928057	Change From Baseline in Serum Iron	59.9 microgram per deciliter (µg/dL)	Standard Deviation 22.4
300 mg LY2928057	Change From Baseline in Serum Iron	95.1 microgram per deciliter (µg/dL)	Standard Deviation 49.8
1000 mg LY2928057	Change From Baseline in Serum Iron	96.3 microgram per deciliter (µg/dL)	Standard Deviation 51.9

Secondary

Number of Participants Forming Antibody to LY2928057

Time frame: Baseline through Day 85

Population: The analysis population included all randomized participants who received at least 1 dose of LY2928057 and antibody titer results.

Arm	Measure	Value (NUMBER)
Placebo	Number of Participants Forming Antibody to LY2928057	0 participants
30 mg LY2928057	Number of Participants Forming Antibody to LY2928057	3 participants
100 mg LY2928057	Number of Participants Forming Antibody to LY2928057	2 participants
300 mg LY2928057	Number of Participants Forming Antibody to LY2928057	5 participants
1000 mg LY2928057	Number of Participants Forming Antibody to LY2928057	4 participants

Secondary