Dose-ranging Study to Evaluate the Efficacy, Safety, and Tolerability of Maridebart Cafraglutide in Adult Subjects With 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

22 Nov 2024 → ongoing

Decision date (initial)

2024-11-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Amgen Inc.

External identifiers

EU CT number

2024-513539-25-00

WHO UTN

U1111-1306-7881

ClinicalTrials.gov

NCT06660173

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response

To assess the dose-response relationship of maridebart cafraglutide on glucose control compared with placebo

Secondary objectives 10

1. To assess the effect of maridebart cafraglutide on body weight
2. To assess the effect of maridebart cafraglutide on reaching specific HbA1c targets
3. To assess the effect of maridebart cafraglutide on achieving specific categories of body weight reduction
4. To assess the effect of maridebart cafraglutide on fasting glucose
5. To assess the effect of maridebart cafraglutide on lipids
6. To assess the effect of maridebart cafraglutide on blood pressure
7. To characterize the pharmacokinetics (PK) of maridebart cafraglutide
8. To assess the safety and tolerability of maridebart cafraglutide
9. To evaluate the immunogenicity of maridebart cafraglutide
10. To assess the effect of maridebart cafraglutide on systemic inflammation

Conditions and MedDRA coding

Type 2 Diabetes Mellitus

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Subject has provided informed consent before initiation of any study-specific activities/procedures.
2. Age ≥ 18 years at screening (or ≥ legal age within the country if it is older than 18 years).
3. BMI of ≥ 23 to ≤ 50 kg/m2 at screening
4. Diagnosis of T2DM at least 180 days before screening based on the World Health Organization (WHO) classification
5. HbA1c at screening of ≥ 7.0% (53.0 mmol/mol) and ≤ 10.5% (91.3 mmol/mol).
6. Treatment of T2DM with a stable dose of metformin (either immediate release or extended release, ≥ 1000 mg/day and not more than the locally approved dose) with or without an SGLT2-inhibitor for at least 90 days before screening.
7. Subject is able and willing to comply with the requirements of the study protocol including SMBG and completion of subject diary

Exclusion criteria 5

1. Type 1 diabetes mellitus (T1DM), history of ketoacidosis or hyperosmolar state/coma, or any other type of diabetes, except T2DM.
2. Fasting glucose > 270 mg/dL (15.0 mmol/L) at screening.
3. History of proliferative diabetic retinopathy, diabetic macular edema, or non-proliferative diabetic retinopathy that requires acute treatment (based on a fundoscopic examination performed by an ophthalmologist or another suitably qualified healthcare provider [eg, optometrist] within 90 days before screening or in the period between screening and randomization).
4. Change in body weight > 5 kg within 90 days before screening, per subject report or medical records.
5. One or more episode of severe hypoglycemia within 180 days before screening, as defined by the occurrence of neuroglycopenic symptoms requiring the assistance of another person for recovery, or history of hypoglycemia unawareness or poor recognition of hypoglycemic symptoms.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline to week 24 in hemoglobin A1c (HbA1c)

Secondary endpoints 10

1. Percent change from baseline to week 24 in body weight
2. Achieving HbA1c < 7.0% at week 24 Achieving HbA1c ≤ 6.5% at week 24
3. Achieving ≥ 5% reduction in body weight from baseline at week 24 Achieving ≥ 10% reduction in body weight from baseline at week 24
4. Change from baseline to week 24 in fasting glucose
5. Percent changes from baseline to week 24 in total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoproteincholesterol (HDL-C), non-high density lipoprotein cholesterol (non-HDL-C), very-low-density lipoprotein cholesterol (VLDL-C), triglycerides, and free fatty acids (FFA)
6. Changes from baseline to week 24 in systolic blood pressure (SBP) and diastolic blood pressure (DBP)
7. Plasma maridebart cafraglutide concentrations including observed predose plasma concentration (Cpredose) at week 20 and, if available, maximum observed plasma concentration (Cmax) as defined by week 20 day 5 to 14 postdose sample
8. Incidence of treatment-emergent adverse events and serious adverse events
9. Incidence of anti-maridebart cafraglutide antibody formation including neutralizing antibodies against native glucagon-like peptide 1 (GLP-1)
10. Change from baseline to week 24 in high-sensitivity C-reactive protein (hs-CRP)

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

91320-1730

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 8

Locations

8 EU/EEA countries · 41 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 84 files

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

Application history

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