A Study of HDM1005 in Participants With T2DM Not Controlled With Metformin Alone or in Combination With a Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor

Hangzhou Zhongmei Huadong Pharmaceutical

Status and phase: Not yet enrolling; Phase 3

Conditions: Type 2 Diabetes

Treatments: Drug: Mazdutide; Drug: HDM1005 1; Drug: HDM1005 2

Study type: Interventional

Funder types: Industry

Identifiers

NCT07417306

HDM1005-303

Details and patient eligibility

About

This study is a multicenter, randomized, open-label, parallel-group, phase 3 clinical trial aimed at evaluating the efficacy and safety of HDM1005 versus active comparator in subjects with Type 2 Diabetes Mellitus (T2DM) Inadequate Glycemic Control by Metformin Monotherapy or in Combination With a Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor.

A total of 912 subjects will be enrolled. All subjects will be stratified by baseline HbA1c levels (≤8.5% or >8.5%) and metformin monotherapy (yes or no), then randomized 1:1:1 to: Group 1 (HDM1005), Group 2 (HDM1005), and Group 3 (active comparator), with 304 subjects in each treatment group. All treatment groups will implement dose titration to achieve the target dose.

The study consists of: up to 2-week screening, 2-week run-in, 40-week core treatment, 12-week extension treatment, and 4-week follow-up, totaling 60 weeks. The end-of-study visit will be conducted 28 days after the last administration cycle.

Enrollment: 912 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Confirmed as Type 2 Diabetes Mellitus (T2DM) for at least 12 weeks and on a stable dosage of metformin alone or in combination with an SGLT2 inhibitor for at least 12 weeks prior to screening.
2. Hemoglobin A1c (HbA1c) ≥7.5% and ≤11.0% (local laboratory) at screening; and ≥7.0% and ≤11.0% (central laboratory) at randomization.
3. Body Mass Index (BMI) ≥22.5 kg/m2.

Exclusion criteria

1. Other types of diabetes besides T2DM.
2. Acute complications of diabetes (such as diabetic ketoacidosis, diabetic lactic acidosis, or hyperosmolar non-ketotic coma) occurred within 24 weeks prior to signing the Informed Consent Form (ICF).
3. History of a level 3 hypoglycemic episode or a history of asymptomatic hyp oglycemic episodes within 24 weeks prior to signing the ICF.
4. History or family history of medullary thyroid carcinoma (MTC), thyroid C-cell hyperplasia, or multiple endocrine neoplasia type 2 (MEN2).
5. History of acute or chronic pancreatitis; or presence of risk factors for pancreatitis; or history of symptomatic gallbladder disease requiring treatment per investigator's assessment within 24 weeks prior to signing the ICF.
6. Investigator determines that the subject has a condition or disease affecting gastric emptying or gastrointestinal nutrient absorption, such as weight-loss surgery or other gastric resections, irritable bowel syndrome, dyspepsia, or gastroparesis.
7. Use of antidiabetic medications within 12 weeks prior to signing the ICF, with the exception of metformin monotherapy or combination therapy with an SGLT2 inhibitor; excluding short-term insulin use (cumulative duration ≤7 days) for concomitant illness, stress, or perioperative periods.
8. Hemoglobin (Hb) <100 g/L (female) or <110 g/L (male).
9. FPG ≥13.9 mmol/L.
10. Aspartate aminotransferase (AST) >3× upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3× ULN.
11. Total bilirubin >1.5× ULN.
12. Fasting triglyceride (TG) >5.6 mmol/L (500 mg/dL).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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912 participants in 3 patient groups

Experimental group: HDM1005 1

Experimental group

Description:

HDM1005 administered subcutaneously (SC)

Treatment:

Drug: HDM1005 1

Experimental group: HDM1005 2

Experimental group

Description:

HDM1005 administered SC

Treatment:

Drug: HDM1005 2

Active Comparator: Mazdutide

Active Comparator group

Description:

Mazdutide administered SC

Treatment:

Drug: Mazdutide