MIST (Metabolic Intervention With Semaglutide and THR-β Therapy) Trial

A Phase 2a, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of ECC4703 as an Adjunct to Semaglutide in Adults With Obesity

The primary objective of this trial is to evaluate the effect of oral ECC4703 on body weight reduction and in a sub-study on liver fat content as assessed by change in magnetic resonance imaging proton density fat fraction (MRI-PDFF) at Week 20.

Study Overview

• Status: Not yet recruiting
• Conditions: Weight Management; Adult Obesity
• Intervention / Treatment: Drug: ECC4703; Drug: Semaglutide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Eccogene Clinical Trials; Phone Number: +1-617-807-4087; Email: contact@eccogene.com

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Central Research Associates - Flourish - PPDS
  • California
    • Anaheim, California, United States, 92081
      • Anaheim Clinical Trials LLC - Anaheim - CenExel - PPDS
    • Los Alamitos, California, United States, 90720
      • Collaborative Neuroscience Network - Los Alamitos- CenExel - PPDS
  • Florida
    • Melbourne, Florida, United States, 32934
      • AES - DRS - Optimal Research Florida - Melbourne
    • Tampa, Florida, United States, 33613
      • ForCare Clinical Research - CenExel FCR - PPDS
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center for Medical Research - CenExel ACMR - PPDS
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta - CenExel - PPDS
  • Minnesota
    • Richfield, Minnesota, United States, 55423
      • AES - DRS - Synexus Clinical Research US, Inc. - Richfield - Minneapolis
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Velocity Clinical Research (3345 N 107th St) - Omaha - Nebraska - PPDS
  • North Carolina
    • Durham, North Carolina, United States, 27701
      • Velocity Clinical Research - Durham - PPDS
  • Ohio
    • Cincinnati, Ohio, United States, 45246
      • Velocity Clinical Research - Cincinnati (Springdale) - Ohio - PPDS
  • Rhode Island
    • East Greenwich, Rhode Island, United States, 02818
      • Velocity Clinical Research - Providence - PPDS
  • Texas
    • Dallas, Texas, United States, 75230
      • Velocity Clinical Research - Dallas - PPDS
    • San Antonio, Texas, United States, 78229
      • AES - DRS - Synexus Clinical Research US, Inc. - San Antonio
    • San Antonio, Texas, United States, 78229
      • Flourish Research - San Antonio - PPDS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Capable of providing written informed consent and complying with all trial procedures.
2. Willing to comply with contraception requirements (as applicable to males and females of childbearing potential).
3. Obese with BMI ≥30 kg/m^2 and stable body weight within 6 months prior to screening.
4. HbA1c ≤6.5%.
5. Estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m^2 (per CKD-EPI 2021 formula).
6. If participant consents to enter the imaging substudy, has liver fat content by MRI-PDFF >8% at baseline (Week 9).

Exclusion Criteria:

1. History or current diagnosis of type 1 or type 2 diabetes mellitus.
2. Weight change >5% of total body weight within 6 months prior to screening or planned initiation of a weight loss program or use of weight-altering medication.
3. Obesity induced by endocrine disorders such as Cushing's syndrome or monogenic or syndromic obesity such as Prader-Willi syndrome.
4. Use of GLP-1 agonist treatment within the last 6 months prior to screening.
5. History or current evidence of a pituitary disorder.
6. Have current treatment with or history (within 3 months prior to screening) of treatment with medications that may cause significant weight gain.
7. ALT or AST >1.5×ULN, or ALP >1.5×ULN at screening.
8. Documented evidence or clinical signs/symptoms of advanced liver disease including liver cirrhosis, portal hypertension, or hepatic decompensation.
9. History of significant alcohol consumption for >3 consecutive months within a year prior to screening.
10. Current or past therapy with THR-β agonists (eg, resmetirom).
11. Active untreated hyperthyroidism or hyperthyroidism currently treated with antithyroid medications including methimazole or propylthiouracil.
12. Clinically significant thyroid dysfunction including uncontrolled hypothyroidism or hyperthyroidism.
13. History of bariatric surgery, fitting of a weight loss device, or intestinal bypass surgery within 5 years prior to screening.
14. History of major surgery within 8 weeks prior to screening.
15. Clinically relevant acute or chronic medical condition or unstable disease of the cardiovascular, gastrointestinal, hepatic, renal, endocrine, pulmonary, neurologic, psychiatric, immune or dermatologic system.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: ECC4703 + semaglutide; ECC4703 orally QD + semaglutide SC once weekly	Drug: ECC4703; orally QD; Drug: Semaglutide; SC once weekly
Placebo Comparator: Arm 2: Placebo + semaglutide; Placebo orally QD + semaglutide SC once weekly	Drug: Semaglutide; SC once weekly; Drug: Placebo; orally QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage Change in Body Weight from Baseline (Week 9) to Week 20	Baseline (Week 9) to Week 20
Proportion of Participants Achieving ≥5% Reduction in Body Weight from Baseline (Week 9) to Week 20	Baseline (Week 9) to Week 20
Absolute Change in Liver Fat Content as Measured by MRI-PDFF in Participants With Hepatic Steatosis	Baseline (Week 9) to Week 20
Percentage Change in Liver Fat Content as Measured by MRI-PDFF in Participants With Hepatic Steatosis	Baseline (Week 9) to Week 20
Proportion of Participants With ≥30% Relative Reduction in Liver Fat Content as Measured by MRI-PDFF	Baseline (Week 9) to Week 20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Percentage Lean Mass as Measured by DXA		Baseline (Week 9) to Week 20
Change in Percentage Total Body Fat Mass as Measured by DXA		Baseline (Week 9) to Week 20
Change in Percentage Visceral Fat Mass as Measured by DXA		Baseline (Week 9) to Week 20
Change in Glycemic Parameters from Baseline (Week 9) to Week 20	Change in HbA1c and fasting plasma glucose levels from baseline (Week 9) to Week 20	Baseline (Week 9) to Week 20
Change in Lipid Parameters from Baseline (Week 9) to Week 20		Baseline (Week 9) to Week 20
Change in Body Weight (kg) from Baseline (Week 9) to Week 20		Baseline (Week 9) to Week 20
Proportion of Participants Achieving ≥2% and ≥3% Reduction in Body Weight from Baseline (Week 9) to Week 20		Baseline (Week 9) to Week 20
Change in Alanine Aminotransferase (ALT) Levels from Baseline (Week 9) to Week 20		Baseline (Week 9) to Week 20
Change in Aspartate Aminotransferase (AST) Levels from Baseline (Week 9) to Week 20		Baseline (Week 9) to Week 20
Change in Alkaline Phosphatase (ALP) Levels from Baseline (Week 9) to Week 20		Baseline (Week 9) to Week 20
Change in Gamma-Glutamyl Transferase (GGT) Levels from Baseline (Week 9) to Week 20		Baseline (Week 9) to Week 20
Frequency of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)		From first dose through Week 20 (or end of study visit)
Severity of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)		From first dose through Week 20 (or end of study visit)
Laboratory Safety Evaluations	changes in clinical laboratory parameters, including hematology, serum chemistry, and urinalysis.	Baseline through Week 20
Changes in 12-Lead Electrocardiogram (ECG) Parameters	Change in QT Interval, etc	Baseline through Week 20
Changes in Vital Signs Findings	including blood pressure, etc	Baseline through Week 20
Changes in Physical Examination Findings	including blood pressure, etc	Baseline through Week 20

Collaborators and Investigators

• Sponsor: Eccogene

Study record dates

Study Major Dates

• Study Start (Estimated): March 13, 2026
• Primary Completion (Estimated): November 20, 2026
• Study Completion (Estimated): November 20, 2026

Study Registration Dates

• First Submitted: March 5, 2026
• First Submitted That Met QC Criteria: March 26, 2026
• First Posted (Actual): April 1, 2026

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Obesity; GLP-1; Semaglutide; Weight Management; MIST; THR-β; ECC4703
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; semaglutide
• Other Study ID Numbers: EC0011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No