Multiple Ascending Dose Study of AMG 598 in Adults With Obesity

NCT03757130 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 20170139
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 4

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.

Conditions

Obesity

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• Maximum Observed Concentration (Cmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57

  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

  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

  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

  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

  Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, and 85

Study Arms (8)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Placebo + Liraglutide

ACTIVE COMPARATOR

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; Drug: Liraglutide

AMG 598 70 mg

EXPERIMENTAL

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 70 mg + Liraglutide

EXPERIMENTAL

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: AMG 598; Drug: Liraglutide

AMG 598 210 mg

EXPERIMENTAL

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

Drug: AMG 598

AMG 598 210 mg + Liraglutide

EXPERIMENTAL

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: AMG 598; Drug: Liraglutide

AMG 598 420 mg

EXPERIMENTAL

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

Drug: AMG 598

AMG 598 420 mg + Liraglutide

EXPERIMENTAL

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: AMG 598; Drug: Liraglutide

Interventions

AMG 598 DRUG

AMG 598 administered by subcutaneous injection

AMG 598 210 mg; AMG 598 210 mg + Liraglutide; AMG 598 420 mg; AMG 598 420 mg + Liraglutide; AMG 598 70 mg; AMG 598 70 mg + Liraglutide

Placebo DRUG

Placebo matching to AMG 598 administered by subcutaneous injection

Placebo; Placebo + Liraglutide

Liraglutide DRUG

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.

Also known as: Saxenda®

AMG 598 210 mg + Liraglutide; AMG 598 420 mg + Liraglutide; AMG 598 70 mg + Liraglutide; Placebo + Liraglutide

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Stable on liraglutide, depending on cohort

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (4)

William D Summers MD LLC

Birmingham, Alabama, 35235, United States

Location

Orange County Research Center

Tustin, California, 92780, United States

Location

QPS Miami Research Associates

South Miami, Florida, 33143, United States

Location

Dallas Diabetes and Endocrine Center

Dallas, Texas, 75230, United States

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Obesity

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blind study
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2018
• First Posted: November 28, 2018
• Study Start: November 26, 2018
• Primary Completion: December 16, 2019
• Study Completion: December 16, 2019
• Last Updated: September 14, 2023
• Results First Posted: September 14, 2023

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

US (4)