MOTS-c for Improving Insulin Sensitivity in Adults With Prediabetes and Overweight/Obesity

NCT07505745 | Recruiting Phase 2 DMC

• 1 other identifier: EX-MOTS-2A-001
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase 2a study evaluates whether 12 weeks of treatment with investigational MOTS-c improves insulin sensitivity compared with placebo in adults with prediabetes and overweight/obesity. Participants are randomized 1:1 to MOTS-c or placebo, receive standardized lifestyle counseling, and are followed for safety through Week 16.

Conditions

Prediabetes; Insulin Resistance; Overweight/Obesity

Keywords

MOTS-c; mitochondrial-derived peptide; MDP; insulin sensitivity; AMPK; prediabetes; metabolic syndrome; OGTT; HbA1c

Outcome Measures

Primary Outcomes (2)

• Change from baseline in OGTT-derived insulin sensitivity (Matsuda Index)

  12 Weeks

• Incidence of treatment-emergent adverse events (TEAEs)

  16 weeks

Secondary Outcomes (4)

• Change from baseline in HbA1c.

  12 Weeks

• Change from baseline in fasting glucose

  12 weeks

• Change from baseline in 2-hour plasma glucose during 75 g OGTT.

  12 weeks

• Immunogenicity (anti-drug antibodies, if applicable).

  16 weeks

Study Arms (2)

MOTS-c

EXPERIMENTAL

Participants receive investigational MOTS-c plus standardized lifestyle counseling.

Drug: MOTS-c (MDP); Other: Route Subcutaneous injection; Other: Regimen

Placebo

PLACEBO COMPARATOR

Participants receive matching placebo plus standardized lifestyle counseling.

Drug: Placebo; Other: Route Subcutaneous injection; Other: Regimen

Interventions

Route Subcutaneous injection OTHER

injection

MOTS-c; Placebo

Regimen OTHER

Fixed dose once daily for 12 weeks

MOTS-c; Placebo

MOTS-c (MDP) DRUG

Drug: MOTS-c (MDP)

MOTS-c

Placebo DRUG

Drug: Placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• Age 18 to 65 years at the time of consent.
• Body mass index (BMI) 27.0 to 40.0 kg/m\^2.
• Prediabetes documented at screening by any of the following: (a) HbA1c 5.7% to 6.4%; (b) fasting plasma glucose 100 to 125 mg/dL; or (c) 2-hour plasma glucose 140 to 199 mg/dL during a 75 g OGTT.
• Stable body weight (less than 5% change) for at least 3 months prior to screening.
• Willingness to maintain stable diet and physical activity patterns during the 12-week treatment period.
• For participants of childbearing potential: agreement to use highly effective contraception for the study duration and for a protocol-specified period after last dose.
• Ability to understand and sign informed consent.

You may not qualify if:

• Diabetes mellitus (e.g., HbA1c 6.5% or higher, fasting plasma glucose 126 mg/dL or higher, or 2-hour glucose 200 mg/dL or higher at screening).
• Use of glucose-lowering medications (including metformin, GLP-1 receptor agonists, SGLT2 inhibitors) within 3 months prior to screening.
• History of bariatric surgery or planned weight-loss surgery during the study period.
• Clinically significant cardiovascular disease within 6 months (e.g., myocardial infarction, stroke, unstable angina) or uncontrolled hypertension.
• Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m\^2, clinically significant hepatic disease, or ALT/AST \> 2.5x upper limit of normal at screening.
• Active malignancy requiring treatment (except adequately treated non-melanoma skin cancer).
• Pregnant, breastfeeding, or planning pregnancy during the study period.
• Known hypersensitivity to peptide therapeutics or any component of the investigational product formulation.
• Any condition that, in the investigator's judgment, would interfere with study participation or interpretation of results (e.g., inability to comply with study procedures).

Sponsors & Collaborators

• Hudson Biotech: lead

Study Sites (1)

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

RECRUITING

MeSH Terms

Conditions

Prediabetic State; Insulin Resistance; Overweight; Obesity; Metabolic Syndrome

Interventions

dipeptidase 1; Clinical Protocols

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics; Epidemiologic Study Characteristics; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation

Central Study Contacts

Seni S Lu, Phd

CONTACT

+86 13076790030; Seni-Lu@beijing-biotech.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: MOTS-c and placebo are identical in appearance and packaging. Randomization codes are held by an unblinded pharmacist/interactive response system; participants, site staff, investigators, and outcome assessors remain blinded until database lock (except for emergency unblinding).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Two-arm, multicenter, randomized, double-blind, placebo-controlled, parallel-group design (1:1 allocation).

Study Record Dates

• First Submitted: March 14, 2026
• First Posted: April 1, 2026
• Study Start: February 2, 2026
• Primary Completion (Estimated): February 14, 2027
• Study Completion (Estimated): May 17, 2028
• Last Updated: April 1, 2026

Record last verified: 2026-03

Locations

CN (1)