Dose-ranging Study to Evaluate the Efficacy, Safety, and Tolerability of AMG 133 in Adult Subjects With Overweight or Obesity, With or Without Type 2 Diabetes Mellitus.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amgen Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

10 Mar 2023 → 16 Dec 2025

Decision date (initial)

2024-07-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Amgen Inc.

External identifiers

EU CT number

2023-510470-13-00

EudraCT number

2022-002470-86

WHO UTN

U1111-1304-5641

ClinicalTrials.gov

NCT05669599

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response

To compare and assess the dose response of 3 selected doses of AMG 133 compared with placebo, on inducing and maintaining weight loss from baseline at week 52 in subjects with overweight or obesity without diabetes mellitus (cohort A) and in subjects with overweight or obesity with type 2 diabetes mellitus (cohort B)

Secondary objectives 11

1. To evaluate the effect of AMG 133 on achieving specific categories of body weight loss from baseline at week 52 in cohorts A and B
2. To evaluate the effect of AMG 133 on glucose metabolism in cohorts A and B
3. To characterize the pharmacokinetics (PK) properties of AMG 133
4. To evaluate the effect of AMG 133 on waist circumference
5. To assess the treatment effect of dose-escalation regimens
6. To evaluate the effect of AMG 133 on systolic blood pressure (SBP).
7. To evaluate the effect of AMG 133 on body composition in a subpopulation
8. To evaluate the effect of AMG 133 on a marker of inflammation
9. To evaluate the effect of AMG 133 on body mass index (BMI)
10. To evaluate the effect of AMG 133 on lipid parameters
11. To evaluate the effect of AMG 133 on diastolic blood pressure (DBP)

Conditions and MedDRA coding

Overweight and Obesity

Study design 5 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share 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. Information on IPD sharing Access Criteria, Time Frame and Supporting Information Type is available on ClinicalTrials.gov (https://clinicaltrials.gov/study/NCT05669599) and on the Amgen Clinical Trials portal (http://www.amgen.com/datasharing).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
2. Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years).
3. Subject has a BMI ≥ 27 kg/sq.m at screening
4. Subject has had at least 1 unsuccessful attempt at weight loss by diet and exercise in the opinion of the investigator.
5. For subjects in cohort A only, presence of at least 1 of the following weight-related complications: hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease; or BMI ≥ 30 kg/sq.m
6. For subjects in cohort A only, HbA1c < 6.5% (< 48 mmol/mol) at screening without a diagnosis of type 1 or 2 diabetes mellitus.
7. For subjects in cohort B only, HbA1c ≥ 7% and ≤ 10% (53 to 86 mmol/mol) at screening with an established diagnosis of type 2 diabetes mellitus for ≥ 180 days prior to screening.
8. For subjects in cohort B only, either treated with diet and exercise alone or on stable (at least 90 days prior to screening) treatment with metformin, a sulfonylurea, or a sodium-glucose cotransporter 2 (SGLT2) inhibitor as monotherapy or combination therapy, per approved local label.

Exclusion criteria 8

1. Subjects with type 1 diabetes mellitus, history of ketoacidosis or hyperosmolar state/coma, or any other types of diabetes except type 2 diabetes mellitus (for cohort B only).
2. History of proliferative diabetic retinopathy, diabetic macular edema, or nonproliferative diabetic retinopathy that requires acute treatment.
3. For the subjects in the DXA substudy only, body weight greater than the local DXA scanner capacity at screening.
4. Change in body weight > 5 kg within 90 days before screening per subject report or medical records.
5. For subjects in cohort B only, fasting glucose > 270 mg/dL (15.0 mmol/L) at screening.
6. Any of the following within the last 6 months prior to screening: myocardial infarction, unstable angina, coronary artery bypass graft, percutaneous coronary intervention (diagnostic angiograms are permitted), transient ischemic attack, cerebrovascular accident, or decompensated congestive heart failure; or currently have New York Health Association Class III or IV heart failure.
7. Uncontrolled thyroid disease, defined as TSH > 6.0 mIU/L or < 0.4 mIU/L as measured by central laboratory at screening. Subjects who received treatment for hypothyroidism are permitted in the study, if their thyroid hormone replacement dose has been stable for at least 90 days and their TSH at screening is within the above range.
8. A corrected QT interval (QTc) of > 450 msec in males or > 470 msec in females at screening as assessed by the investigator, or history of long QT syndrome

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent change from baseline to week 52 in body weight

Secondary endpoints 5

1. Achieving ≥ 5%, ≥ 10%, ≥ 15%, ≥ 20% reduction in body weight from baseline at week 52 (yes/no)
2. Change from baseline to week 52 in hemoglobin A1c (HbA1c), in fasting serum insulin, in fasting plasma glucose, in Homeostasis Model Assessment for insulin resistance (HOMA2-IR), in Homeostasis Model Assessment for steady state beta cell function (HOMA2-%B)
3. PK parameters for AMG 133 including, but not limited to maximum observed plasma concentration (Cmax), and area under the concentration-time curve (AUC)
4. Change from baseline to week 52 in waist circumference, in body weight, in SBP, in DBP, in BMI, in body composition (eg, fat mass, lean mass) using dual-energy X-ray absorptiometry (DXA) for a subset of subjects
5. Percent change from baseline to week 52 in high-sensitivity C-reactive protein (hs-CRP), in low-density lipoprotein cholesterol (LDL-C), in total cholesterol, in high-density lipoprotein cholesterol (HDL-C), in non-HDL-C, in very-low-density lipoprotein cholesterol (VLDL-C), in triglycerides, in free fatty acids (FFA)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amgen Inc.

Sponsor organisation

Amgen Inc.

Address

1 Amgen Center Drive

City

Thousand Oaks

Postcode

91320-1799

Country

United States

Scientific contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Public contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Third parties 4

Locations

5 EU/EEA countries · 19 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 71 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications