A Study to Evaluate the Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of AMG 592 in Healthy Participants

A Randomized, Double-blind, Placebo-controlled, Single-ascending Dose Study to Evaluate the Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of AMG 592 in Healthy Subjects

The primary objective of this study is to evaluate the safety, tolerability and immunogenicity profile of single and multiple dose administrations of AMG 592 in healthy participants.

Study Overview

• Status: Completed
• Conditions: Chronic Graft-versus-host Disease (cGVHD)
• Intervention / Treatment: Drug: AMG 592; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Aventura, Florida, United States, 33180
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Males must agree to practice an acceptable method of effective birth control while on study through 2 weeks after receiving the dose of study drug.
• Males must be willing to abstain from sperm donation while on study through 2 weeks after receiving the (last [multiple dose studies]) dose of study drug.
• Male and female subjects ≥ 18 and ≤ 55 years of age with a body mass index (BMI) of ≥ 18.0 and ≤ 32.0 kg/m^2 at the time of screening.
• Females must be of non-reproductive potential (ie, postmenopausal - age ≥ 55 years with cessation of menses for 12 months or more, or according to the definition of "postmenopausal range" for the laboratory involved OR history of hysterectomy; OR history of bilateral oophorectomy).

Exclusion Criteria:

• Positive Hepatitis B Surface Antigen (HepBsAg) (indicative of chronic Hepatitis B) or detectable Hepatitis C virus Ribonucleic acid (RNA) by Polymerase Chain Reaction (PCR) (indicative of active Hepatitis C - screening is generally done by Hepatitis C Antibody (HepCAb), followed by Hepatitis C virus RNA by PCR if HepCAb is positive).
• Positive results for Human Immunodeficiency Virus (HIV).
• Participant has a history of residential exposure to tuberculosis without a documented history of prophylactic treatment of tuberculosis or participant has a positive purified protein derivative (PPD) or QuantiFERON or T-Spot test at Screening. Participants with a documented negative PPD or QuantiFERON or T-Spot test within 4 weeks prior to screening who have no known tuberculosis exposure and have not traveled to an area with tuberculosis do not need to have a test performed at screening.
• Currently receiving treatment in another investigational device or drug study, or less than 30 days or less than 5 half-lives, whichever is longer, since ending treatment on another investigational device or drug study.
• Malignancy except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ within the last 5 years.
• Any active infection for which systemic anti-infectives were used within 4 weeks prior to Day 1.
• Females who are lactating/breastfeeding or who plan to breastfeed while on study through 2 weeks after receiving the dose of study drug.
• Female participants with a positive pregnancy test.
• Males with partners who are pregnant or planning to become pregnant while the participant is on study through 2 weeks after receiving the dose of study drug.
• Has any significant abnormality during the screening physical examination, electrocardiogram (ECG), or laboratory evaluation that in the opinion of the Investigator, in consultation with the Amgen Medical Monitor, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
• Unwilling or unable to abstain from alcohol consumption within 48 hours prior to each visit (including Screening).
• Is a current smoker, has used any nicotine or tobacco containing products (including but not limited to: snuff, chewing tobacco, cigars, cigarettes, pipes, or nicotine patches) within the last 6 months from Screening, and cumulative smoking history is ≥ 10 pack years.
• Unwilling or unable to refrain from strenuous exercise (eg, heavy lifting, weight training, and aerobics) for 72 hours prior to each visit that includes blood collection.
• Has donated or lost ≥ 500 mL of blood or plasma within 8 weeks of administration of the first dose of IP.
• Participants with a known history of autoimmune disease.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AMG 592: Dose 1; Administered as a single dose subcutaneous (SC) injection.	Drug: AMG 592; Administered as SC injection
Experimental: AMG 592: Dose 2; Administered as a single dose SC injection.	Drug: AMG 592; Administered as SC injection
Experimental: AMG 592: Dose 3; Administered as a single dose SC injection.	Drug: AMG 592; Administered as SC injection
Experimental: AMG 592: Dose 4; Administered as a single dose SC injection.	Drug: AMG 592; Administered as SC injection
Experimental: AMG 592: Dose 5; Administered as a single dose SC injection.	Drug: AMG 592; Administered as SC injection
Experimental: AMG 592: Dose 6; Administered as a single dose SC injection.	Drug: AMG 592; Administered as SC injection
Experimental: AMG 592: Dose 7; Administered as a single dose SC injection.	Drug: AMG 592; Administered as SC injection
Experimental: AMG 592: Dose 8; Administered as a single dose SC injection.	Drug: AMG 592; Administered as SC injection
Placebo Comparator: Placebo; Administered as SC injection.	Other: Placebo; Administered as SC injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Treatment-emergent Adverse Events (TEAEs)	Any clinically significant changes in physical examinations, clinical laboratory tests and vital signs will be recorded as TEAEs.	Day 1 up to Day 57
Number of Participants with Anti-AMG 592 Antibodies		Day 1 up to Day 57
Fold Change from Baseline in Absolute Cell Counts of Regulatory T Cells (Tregs)		One week after AMG 592 administration (up to 7 days)
Fold Change from Baseline in Absolute Cell Counts of Conventional T Cells (Tcons)		One week after AMG 592 administration (up to 7 days)
Fold Change from Baseline in Absolute Cell Counts of Natural Killer Cells (NKs)		One week after AMG 592 administration (up to 7 days)

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Serum Concentration (Cmax) of AMG 592	Day 1 up to Day 57
Time of Maximum Observed Concentration (tmax) of AMG 592	Day 1 up to Day 57
Area Under the Concentration-time Curve (AUC) of AMG 592	Day 1 up to Day 57

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2015
• Primary Completion (Actual): June 16, 2017
• Study Completion (Actual): July 28, 2017

Study Registration Dates

• First Submitted: May 16, 2023
• First Submitted That Met QC Criteria: May 16, 2023
• First Posted (Actual): May 24, 2023

Study Record Updates

• Last Update Posted (Actual): May 24, 2023
• Last Update Submitted That Met QC Criteria: May 16, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: AMG 592; Chronic Graft-versus-Host Disease; Inflammatory Conditions
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Bronchiolitis Obliterans; Bronchiolitis; Organizing Pneumonia; Graft vs Host Disease; Bronchiolitis Obliterans Syndrome
• Other Study ID Numbers: 20140324

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No