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Multiple Ascending Dose Study of AMG 598 in Adults With Obesity

Primary Purpose

Obesity

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AMG 598
Placebo
Liraglutide
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Obesity

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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/m2 and less than or equal to 40.0 kg/m2 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

Sites / Locations

  • William D Summers MD LLC
  • Orange County Research Center
  • QPS Miami Research Associates
  • Dallas Diabetes and Endocrine Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Placebo Comparator

Active Comparator

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Placebo

Placebo + Liraglutide

AMG 598 70 mg

AMG 598 70 mg + Liraglutide

AMG 598 210 mg

AMG 598 210 mg + Liraglutide

AMG 598 420 mg

AMG 598 420 mg + Liraglutide

Arm Description

Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for a total of 3 doses.

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.

Participants received 70 mg AMG 598 by subcutaneous injection once every 4 weeks (Q4W) for a total of 3 doses.

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.

Participants received 210 mg AMG 598 by subcutaneous injection once every 4 weeks for a total of 3 doses.

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.

Participants received 420 mg AMG 598 by subcutaneous injection once every 4 weeks for a total of 3 doses.

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.

Outcomes

Primary Outcome Measures

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.
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).

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
November 27, 2018
Last Updated
November 4, 2022
Sponsor
Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT03757130
Brief Title
Multiple Ascending Dose Study of AMG 598 in Adults With Obesity
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
November 26, 2018 (Actual)
Primary Completion Date
December 16, 2019 (Actual)
Study Completion Date
December 16, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantInvestigator
Masking Description
Double-blind study
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for a total of 3 doses.
Arm Title
Placebo + Liraglutide
Arm Type
Active Comparator
Arm Description
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.
Arm Title
AMG 598 70 mg
Arm Type
Experimental
Arm Description
Participants received 70 mg AMG 598 by subcutaneous injection once every 4 weeks (Q4W) for a total of 3 doses.
Arm Title
AMG 598 70 mg + Liraglutide
Arm Type
Experimental
Arm Description
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.
Arm Title
AMG 598 210 mg
Arm Type
Experimental
Arm Description
Participants received 210 mg AMG 598 by subcutaneous injection once every 4 weeks for a total of 3 doses.
Arm Title
AMG 598 210 mg + Liraglutide
Arm Type
Experimental
Arm Description
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.
Arm Title
AMG 598 420 mg
Arm Type
Experimental
Arm Description
Participants received 420 mg AMG 598 by subcutaneous injection once every 4 weeks for a total of 3 doses.
Arm Title
AMG 598 420 mg + Liraglutide
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
AMG 598
Intervention Description
AMG 598 administered by subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo matching to AMG 598 administered by subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Liraglutide
Other Intervention Name(s)
Saxenda®
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-emergent Adverse Events
Description
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.
Time Frame
207 days
Title
Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings
Description
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).
Time Frame
207 days
Secondary Outcome Measure Information:
Title
Maximum Observed Concentration (Cmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57
Description
Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.
Time Frame
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
Title
Time to Maximum Observed Concentration (Tmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57
Description
Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.
Time Frame
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
Title
Dose-normalized Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57
Description
Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.
Time Frame
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
Title
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
Description
Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.
Time Frame
Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, and 85
Title
Dose-normalized AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57
Description
Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.
Time Frame
Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, and 85
Title
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
Description
Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.
Time Frame
Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207
Title
Accumulation Ratio (AR) for Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57
Description
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.
Time Frame
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
Title
Accumulation Ratio of AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57
Description
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.
Time Frame
Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, and 85
Title
Terminal Half-life (T1/2,z) of AMG 598 After Subcutaneous Injection on Day 57
Description
Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.
Time Frame
Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
William D Summers MD LLC
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35235
Country
United States
Facility Name
Orange County Research Center
City
Tustin
State/Province
California
ZIP/Postal Code
92780
Country
United States
Facility Name
QPS Miami Research Associates
City
South Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
Dallas Diabetes and Endocrine Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
http://www.amgen.com/datasharing
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website

Learn more about this trial

Multiple Ascending Dose Study of AMG 598 in Adults With Obesity

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