Multiple Ascending Dose Study of AMG 598 in Adults With Obesity

A Phase 1b, Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 598 in Subjects With Obesity

The main objective of this study is to assess the safety and tolerability of multiple doses of AMG 598 administered alone or in combination with liraglutide in adults with obesity.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Placebo; Drug: Liraglutide; Drug: AMG 598

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235
      • William D Summers MD LLC
  • California
    • Tustin, California, United States, 92780
      • Orange County Research Center
  • Florida
    • South Miami, Florida, United States, 33143
      • QPS Miami Research Associates
  • Texas
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes and Endocrine Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men and women with ages between 18 and 65 years old, inclusive, at time of signing consent
• Body mass index (BMI) between greater than or equal to 30.0 kg/m^2 and less than or equal to 40.0 kg/m^2 at screening
• Except for obesity, otherwise healthy or medically stable per protocol
• Have a stable body weight defined as less than 5 kg self-reported change during the previous 8 weeks prior to screening
• Other Inclusion criteria may apply
• Stable on liraglutide, depending on cohort

Exclusion Criteria:

• History or clinical evidence of diabetes
• Inadequate organ function at screening
• Currently receiving treatment in another investigational device or drug study
• Women who are pregnant/lactating/breastfeeding or who plan to become pregnant/breastfeed while on study through 5 months after receiving the last dose of investigational product
• History or evidence of a clinically significant disorder, condition or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
• A family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2; a personal history of non-familial medullary thyroid carcinoma; confirmed chronic pancreatitis or idiopathic acute pancreatitis, or gallbladder disease (ie, cholelithiasis or cholecystitis) not treated with cholecystectomy, for cohorts receiving liraglutide
• History of major depressive disorder
• Other Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for a total of 3 doses.	Drug: Placebo; Placebo matching to AMG 598 administered by subcutaneous injection
Active Comparator: Placebo + Liraglutide; Participants received placebo subcutaneous injection once every 4 weeks for a total of 3 doses in addition to liraglutide administered by subcutaneous injection once a day for 12 weeks. The starting dose of liraglutide was 0.6 mg/day, increasing in increments of 0.6 mg/day every 7 days to reach the full dosage of 3 mg/day by week 5.	Drug: Placebo; Placebo matching to AMG 598 administered by subcutaneous injection; Drug: Liraglutide; Liraglutide administered by subcutaneous injection. The starting dose is 0.6 mg/day, and increased by 0.6 mg/day dose increment every 7 days, up to the full dosage of 3.0 mg/day by week 5.; Other Names: Saxenda®
Experimental: AMG 598 70 mg; Participants received 70 mg AMG 598 by subcutaneous injection once every 4 weeks (Q4W) for a total of 3 doses.	Drug: AMG 598; AMG 598 administered by subcutaneous injection
Experimental: AMG 598 70 mg + Liraglutide; Participants received 70 mg AMG 598 by subcutaneous injection once every 4 weeks for a total of 3 doses in addition liraglutide administered by subcutaneous injection once a day for 12 weeks. The starting dose of liraglutide was 0.6 mg/day, increasing in increments of 0.6 mg/day every 7 days to reach the full dosage of 3 mg/day by week 5.	Drug: Liraglutide; Liraglutide administered by subcutaneous injection. The starting dose is 0.6 mg/day, and increased by 0.6 mg/day dose increment every 7 days, up to the full dosage of 3.0 mg/day by week 5.; Other Names: Saxenda®; Drug: AMG 598; AMG 598 administered by subcutaneous injection
Experimental: AMG 598 210 mg; Participants received 210 mg AMG 598 by subcutaneous injection once every 4 weeks for a total of 3 doses.	Drug: AMG 598; AMG 598 administered by subcutaneous injection
Experimental: AMG 598 210 mg + Liraglutide; Participants received 210 mg AMG 598 by subcutaneous injection once every 4 weeks for a total of 3 doses in addition to liraglutide administered by subcutaneous injection once a day for 12 weeks. The starting dose of liraglutide was 0.6 mg/day, increasing in increments of 0.6 mg/day every 7 days to reach the full dosage of 3 mg/day by week 5.	Drug: Liraglutide; Liraglutide administered by subcutaneous injection. The starting dose is 0.6 mg/day, and increased by 0.6 mg/day dose increment every 7 days, up to the full dosage of 3.0 mg/day by week 5.; Other Names: Saxenda®; Drug: AMG 598; AMG 598 administered by subcutaneous injection
Experimental: AMG 598 420 mg; Participants received 420 mg AMG 598 by subcutaneous injection once every 4 weeks for a total of 3 doses.	Drug: AMG 598; AMG 598 administered by subcutaneous injection
Experimental: AMG 598 420 mg + Liraglutide; Participants received 420 mg AMG 598 by subcutaneous injection once every 4 weeks for a total of 3 doses in addition to liraglutide administered by subcutaneous injection once a day for 12 weeks. The starting dose of liraglutide was 0.6 mg/day, increasing in increments of 0.6 mg/day every 7 days to reach the full dosage of 3 mg/day by week 5.	Drug: Liraglutide; Liraglutide administered by subcutaneous injection. The starting dose is 0.6 mg/day, and increased by 0.6 mg/day dose increment every 7 days, up to the full dosage of 3.0 mg/day by week 5.; Other Names: Saxenda®; Drug: AMG 598; AMG 598 administered by subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events	The investigator assessed the severity of each adverse event reported during the study. The assessment was based on the Amgen Standard Grading Scale: Mild: Aware of sign or symptom, but easily tolerated. Moderate: Discomfort enough to cause interference with usual activity. Severe: Incapacitating with inability to work or do usual activity. A Serious adverse event is defined as any untoward medical occurrence that, met at least 1 of the following serious criteria; Death;; Was life-threatening;; Required in-patient hospitalization or prolongation of existing hospitalization;; Resulted in persistent or significant disability/incapacity;; Was a congenital anomaly/birth defect;; Other medically important serious event. The investigator also assessed whether each adverse event was related to study drug administration based on clinical judgement.	207 days
Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings	TEAEs due to laboratory, electrocardiogram (ECG) and vital sign findings include any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or electrocardiogram, or vital signs measurements, including those that worsened from baseline, that were considered clinically significant in the medical and scientific judgment of the investigator (ie, not related to progression of underlying disease).	207 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Concentration (Cmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57	Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.	Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207
Time to Maximum Observed Concentration (Tmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57	Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.	Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207
Dose-normalized Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57	Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.	Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207
Area Under the Concentration-time Curve From Time 0 to 28 Days (AUC0-28) for AMG 598 After Subcutaneous Injection on Day 1 and Day 57	Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.	Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, and 85
Dose-normalized AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57	Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.	Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, and 85
Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of AMG 598 After Subcutaneous Injection on Day 57	Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.	Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207
Accumulation Ratio (AR) for Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57	Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL. Accumulation ratio for Cmax = Day 57 Cmax / Day 1 Cmax.	Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207
Accumulation Ratio of AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57	Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL. The accumulation ratio for AUC0-28 = Day 57 AUC0-28 / Day 1 AUC0-28.	Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, and 85
Terminal Half-life (T1/2,z) of AMG 598 After Subcutaneous Injection on Day 57	Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.	Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207

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): November 26, 2018
• Primary Completion (Actual): December 16, 2019
• Study Completion (Actual): December 16, 2019

Study Registration Dates

• First Submitted: November 27, 2018
• First Submitted That Met QC Criteria: November 27, 2018
• First Posted (Actual): November 28, 2018

Study Record Updates

• Last Update Posted (Actual): September 14, 2023
• Last Update Submitted That Met QC Criteria: November 4, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide
• Other Study ID Numbers: 20170139

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 (or other new use) 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, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. 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 link 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