Single Ascending Dose Study of AMG 570 in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to obtain initial information on the safety and tolerability (effects good or bad), pharmacokinetics (what the body does to the drug), and pharmacodynamics (what the drug does to the body) of a single dose of AMG 570.

Official Title
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A Randomized, Double Blind Placebo Controlled, First in Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Subcutaneous Doses of AMG 570 in Healthy Subjects

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Biological: AMG 570
* Biological: AMG 570 Matching Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy as determined by the investigator Normal or clinically acceptable electrocardiogram (ECG) Female subjects must be of documented non-reproductive potential Subjects must be current for all vaccinations Other inclusion criteria may apply Exclusion Criteria: Current or chronic history of liver disease History of active infections History of significant respiratory disorder Evidence of renal disease Other exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMG 570 - 7 mg<br>Participants will receive a single dose 7 mg dose of AMG 570 administered subcutaneously. | Biological: AMG 570<br>* 7 dose levels of AMG 570 administered as single dose subcutaneous in healthy volunteers.<br>* Other names: Active Comparator, Investigational Product, and Study drug;|
| Experimental: AMG 570 - 21 mg<br>Participants will receive a single 21 mg dose of AMG 570 administered subcutaneously. | Biological: AMG 570<br>* 7 dose levels of AMG 570 administered as single dose subcutaneous in healthy volunteers.<br>* Other names: Active Comparator, Investigational Product, and Study drug;|
| Experimental: AMG 570 - 70 mg<br>Participants will receive a single 70 mg dose of AMG 570 administered subcutaneously. | Biological: AMG 570<br>* 7 dose levels of AMG 570 administered as single dose subcutaneous in healthy volunteers.<br>* Other names: Active Comparator, Investigational Product, and Study drug;|
| Experimental: AMG 570 - 140 mg<br>Participants will receive a single 140 mg dose of AMG 570 administered subcutaneously. | Biological: AMG 570<br>* 7 dose levels of AMG 570 administered as single dose subcutaneous in healthy volunteers.<br>* Other names: Active Comparator, Investigational Product, and Study drug;|
| Experimental: AMG 570 - 210 mg<br>Participants will receive a single 210 mg dose of AMG 570 administered subcutaneously. | Biological: AMG 570<br>* 7 dose levels of AMG 570 administered as single dose subcutaneous in healthy volunteers.<br>* Other names: Active Comparator, Investigational Product, and Study drug;|
| Experimental: AMG 570 - 420 mg<br>Participants will receive a single 420 mg dose of AMG 570 administered subcutaneously. | Biological: AMG 570<br>* 7 dose levels of AMG 570 administered as single dose subcutaneous in healthy volunteers.<br>* Other names: Active Comparator, Investigational Product, and Study drug;|
| Experimental: AMG 570 - 700 mg<br>Participants will receive a single 700 mg dose of AMG 570 administered subcutaneously. | Biological: AMG 570<br>* 7 dose levels of AMG 570 administered as single dose subcutaneous in healthy volunteers.<br>* Other names: Active Comparator, Investigational Product, and Study drug;|
| Placebo Comparator: Placebo<br>Participants will receive a single dose of the matching AMG 570 placebo administered subcutaneously. | Biological: AMG 570 Matching Placebo<br>* Placebo administered as single dose subcutaneous in healthy volunteers.<br>* Other names: Placebo, Investigational Product, and Study drug;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | TEAEs were adverse events with an onset after the administration of study treatment. TEAEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limited age appropriate instrumental activities of daily life (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolonged hospitalization indicated; disabling; limited self care ADL. Grade 4 Life-threatening consequences; urgent interventions indicated. Serious adverse events (SAEs) were defined as meeting at least 1 of the following criteria: Results in death (fatal) Immediately life-threatening Requires in-patient hospitalization or prolongation of existing hospitalization Results in persistent or significant disability/incapacity Is a congenital anomaly/birth defect Other medically important serious event | Day 1 to Day 105 | 
| Number of Participants Who Experienced a Clinically Significant Change in Physical Examinations | Physical examinations were performed by the investigator, designated physician, or nurse practitioner. A complete physical examination included, at a minimum, assessment of cardiovascular, respiratory, gastrointestinal and neurological systems. A brief physical examination included assessment of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). | Baseline to Day 105 | 
| Number of Participants Who Experienced a Clinically Significant Change in Vital Signs | Any changes in blood pressure, body temperature, heart rate, and pulse rate that were deemed as clinically significant by the Investigator were reported. | Baseline to Day 105 | 
| Number of Participants Who Experienced a Clinically Significant Change in Clinical Laboratory Safety Tests | Laboratory safety tests included chemistry, hematology, and urinalysis parameters. Clinically significant laboratory safety tests were any events assessed as CTCAE Grade ≥3 at any post-baseline visit. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolonged hospitalization indicated; disabling; limited self care ADL. Grade 4 Life-threatening consequences; urgent interventions indicated. | Baseline to Day 105 | 
| Number of Participants Who Experienced a Clinically Significant Change in Electrocardiograms (ECGs) | Any changes in ECG parameters that were deemed clinically significant by the Investigator were reported. | Baseline to Day 105 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Concentration (Cmax) of AMG 570 | AMG 570 pharmacokinetic (PK) parameters were estimated using non-compartmental analysis. | Pre-dose and 12 hours post-dose on Day 1 and days 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 57, 71 and 105 | 
| Time to Reach Maximum Observed Concentration (Tmax) of AMG 570 | AMG 570 PK parameters were estimated using non-compartmental analysis. | Pre-dose and 12 hours post-dose on Day 1 and days 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 57, 71 and 105 | 
| Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUClast) of AMG 570 | AMG 570 PK parameters were estimated using non-compartmental analysis. | Pre-dose and 12 hours post-dose on Day 1 and days 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 57, 71 and 105 | 
| Area Under the Concentration-time Curve Observed From Time Zero to Infinity (AUCinf) of AMG 570 |  | Pre-dose and 12 hours post-dose on Day 1 and days 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 57, 71 and 105 | 
| Number of Participants With an Anti-AMG 570 Binding Antibody Positive Postbaseline Result | The presence of anti-AMG 570 binding antibodies was assessed using a validated assay. The number and percentage of participants who developed binding anti-AMG 570 antibodies at any postbaseline visit are presented. | Baseline to Day 105 | 
| Mean Peripheral Blood B7-Related Protein-1 (B7RP-1) Receptor Occupancy on Total B Cells | Peripheral B7RP1 (also known as inducible costimulator ligand [ICOSL]) receptor occupancy was calculated from the free ICOSL and total ICOSL measurement from B cells in whole blood. | Day 8; Day 29; Day 57; and Day 105 | 
| Percentage Change From Baseline for Cluster of Differentiation (CD)19+ Total B Cells Counts |  | Baseline to Day 8; Day 29; Day 57 and Day 105 | 
| Percentage Change From Baseline for CD19+ Total B Cells Percentages (%) |  | Baseline to Day 8; Day 29; Day 57 and Day 105 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lupus, Healthy Volunteer, Safety Study, Placebo Control, Phase 1