Single and Multiple Ascending Dose Study of AMG 171 in Subjects With Obesity

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 171 in Subjects With Obesity

To assess the safety and tolerability of AMG 171 as single or multiple doses in subjects with obesity

Study Overview

• Status: Terminated
• Conditions: Obesity
• Intervention / Treatment: Drug: AMG 171; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials
    • Tustin, California, United States, 92780
      • Orange County Research Center
  • Florida
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami, LLC

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

• Males and females with ages between 18 and 65 years old, inclusive
• Except for obesity, otherwise healthy
• Body mass index (BMI) greater than or equal to 30.0 kg/m2 and less than or equal to 40.0 kg/m2 at screening
• Other Inclusion criteria may apply

Exclusion Criteria:

• Currently receiving treatment in another investigational device or drug study
• Women of childbearing potential
• 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
• Other Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A; AMG 171 or placebo, 2 SAD cohorts	Drug: AMG 171; 2 SAD cohorts of 8 subjects per cohort randomized 3:1 in Part A; 1 cohort of 8 subjects 3:1 ratio in Part B; and 24 subjects enrolled into 1 of 3 cohorts with 8 subjects randomized to receive 2 to 3 consecutive doses (titration) 3:1 ratio in Part C.; Drug: Placebo; AMG 171 placebo
Experimental: Part B; AMG 171 or placebo, 1 MAD cohort	Drug: AMG 171; 2 SAD cohorts of 8 subjects per cohort randomized 3:1 in Part A; 1 cohort of 8 subjects 3:1 ratio in Part B; and 24 subjects enrolled into 1 of 3 cohorts with 8 subjects randomized to receive 2 to 3 consecutive doses (titration) 3:1 ratio in Part C.; Drug: Placebo; AMG 171 placebo
Experimental: Part C; AMG 171 or placebo, 3 titration cohorts	Drug: AMG 171; 2 SAD cohorts of 8 subjects per cohort randomized 3:1 in Part A; 1 cohort of 8 subjects 3:1 ratio in Part B; and 24 subjects enrolled into 1 of 3 cohorts with 8 subjects randomized to receive 2 to 3 consecutive doses (titration) 3:1 ratio in Part C.; Drug: Placebo; AMG 171 placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with study treatment. A serious AE (SAE) was an AE meeting at least 1 of the following serious criteria: fatal, life-threatening, required in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability; congenital anomaly/birth defect; other medically important serious event. Clinically significant changes from baseline in laboratory safety tests, vital sign assessments, and 12-lead electrocardiogram assessments were included as TEAEs.	From first dose of IP to end of study, up to Day 207

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Serum Concentration (Cmax) for AMG 171: SAD Cohorts 1 and 1b	Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of pharmacokinetic (PK) parameters. Concentrations below the lower limit of quantification (LLOQ) (50.0 ng/mL) were set to zero before data analysis.	Cohorts 1 and 1b: pre-dose Day 1; 1, 2, 4, and 8 hours post-dose Day 1, Days 2 up to Day 120
Cmax for AMG 171: MAD Cohorts 2 - 5	Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (50.0 ng/mL) were set to zero before data analysis.	Cohort 2: pre-dose Days 1, 15, 29, 43, 57, 71; post-dose Days 5 up to 207; Cohort 3: pre-dose Days 1, 15; post-dose Days 2 up to 85; Cohort 4: pre-dose Days 1, 15, 29; post-dose Days 2 up to 113; Cohort 5: pre-dose Days 1, 8; post-dose Days 2 up to 85
Time of Cmax (Tmax) for AMG 171: SAD Cohorts 1 and 1b	Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (50.0 ng/mL) were set to zero before data analysis.	Cohorts 1 and 1b: pre-dose Day 1; 1, 2, 4, and 8 hours post-dose Day 1, Days 2 up to Day 120
Tmax for AMG 171: MAD Cohorts 2 - 5	Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (50.0 ng/mL) were set to zero before data analysis.	Cohort 2: pre-dose Days 1, 15, 29, 43, 57, 71; post-dose Days 5 up to 207; Cohort 3: pre-dose Days 1, 15; post-dose Days 2 up to 85; Cohort 4: pre-dose Days 1, 15, 29; post-dose Days 2 up to 113; Cohort 5: pre-dose Days 1, 8; post-dose Days 2 up to 85
Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Infinity (AUCinf) for AMG 171: SAD Cohorts 1 and 1b	Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (50.0 ng/mL) were set to zero before data analysis.	Cohorts 1 and 1b: pre-dose Day 1; 1, 2, 4, and 8 hours post-dose Day 1, Days 2 up to Day 120
AUC From Time 0 to 14 Days (AUC0-14) for AMG 171: MAD Cohorts 2 - 4	Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (50.0 ng/mL) were set to zero before data analysis.	Cohort 2: pre-dose Days 1, 15, 29, 43, 57, 71; post-dose Days 5 up to 207; Cohort 3: pre-dose Days 1, 15; post-dose Days 2 up to 85; Cohort 4: pre-dose Days 1, 15, 29; post-dose Days 2 up to 113
AUC From Time 0 to 7 Days (AUC0-7) for AMG 171: MAD Cohort 5	Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (50.0 ng/mL) were set to zero before data analysis.	Cohort 5: pre-dose Days 1, 8; post-dose Days 2 up to 85
Number of Participants With Anti-AMG 171 Antibodies	Serum samples were tested for binding and neutralizing antibodies against human Growth Differentiation Factor 15. Participants with transiently positive for binding or neutralizing antibodies had a negative result at the participant's last time point tested. bAb = binding antibody; nAb = neutralizing antibody; +ve = positive; -ve = negative; BL = baseline.	Cohorts 1 and 1b: Day 1 pre-dose, Days 15, 29, 120; Cohort 2: Days 1, 29, 57 pre-dose, Days 15, 85, 207; Cohort 3: Days 1, 15 pre-dose, Days 29, 57, 85; Cohort 4: Days 1, 15, 29 pre-dose, Days 43, 85, 113; Cohort 5: Days 1, 8 pre-dose, Days 29, 57, 85

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): December 13, 2019
• Primary Completion (Actual): September 10, 2021
• Study Completion (Actual): September 10, 2021

Study Registration Dates

• First Submitted: December 12, 2019
• First Submitted That Met QC Criteria: December 12, 2019
• First Posted (Actual): December 13, 2019

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: April 26, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Obesity
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: 20180224

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 datasharing 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