Single Ascending Dose Study of AMG 570 in Healthy Subjects

Systemic Lupus Erythematosus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02618967
• Other study ID #: 20140322
• Status: Completed
• Phase: Phase 1
• Start date: March 28, 2016
• Est. completion date: December 3, 2018

Study information

• Verified date: May 2024
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: December 3, 2018
• Est. primary completion date: September 6, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Biological:
• AMG 570
7 dose levels of AMG 570 administered as single dose subcutaneous in healthy volunteers.
• AMG 570 Matching Placebo
Placebo administered as single dose subcutaneous in healthy volunteers.

Locations

Country	Name	City	State
United States	Research Site	Evansville	Indiana
United States	Research Site	Madison	Wisconsin
United States	Research Site	Overland Park	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

United States, 

References & Publications (1)

Abuqayyas L, Chen PW, Dos Santos MT, Parnes JR, Doshi S, Dutta S, Houk BE. Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Properties of Rozibafusp Alfa, a Bispecific Inhibitor of BAFF and ICOSL: Analyses of Phase I Clinical Trials. Clin Pharmacol Ther. 2023 Aug;114(2):371-380. doi: 10.1002/cpt.2929. Epub 2023 May 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Percentage Change From Baseline for CD19+ Total B Cells Percentages (%)		Baseline to Day 8; Day 29; Day 57 and Day 105

External Links

•   AmgenTrials clinical trials website