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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
Lead sponsor
Asset
Semaglutide
Subcutaneous · GLP-1 agonist
Listed sites
15
Recruiting sites
—
Enrollment
160
estimated
Study population
MASH / NAFLD / liver fibrosis, Obesity / overweight
Key I/E criteria
•BMI ≥30•HbA1c ≤6.5%•eGFR ≥60
Primary endpoints
•Body weight, % change•≥5% weight-loss responders•Liver fat content, change
Footprint
Where this trial recruits
Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.
Identifiers
Registered as
Timeline
Milestones
Assets
Investigational agents
Study populations
Who this study enrolls
Eligibility
Who can enroll
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.
Endpoints (22)
What's being measured
Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.
Coverage by outcome category
Weight & body composition
7 endpointsPercentage Change in Body Weight from Baseline (Week 9) to Week 20
Time frame:Baseline (Week 9) to Week 20
Body weight, % change
percent change from baseline, improvement
Proportion of Participants Achieving ≥5% Reduction in Body Weight from Baseline (Week 9) to Week 20
Time frame:Baseline (Week 9) to Week 20
≥5% weight-loss responders
threshold achievement, improvement
Change in Percentage Lean Mass as Measured by DXA
Time frame:Baseline (Week 9) to Week 20
Lean mass
change from baseline, improvement
Change in Percentage Total Body Fat Mass as Measured by DXA
Time frame:Baseline (Week 9) to Week 20
Total fat mass
change from baseline, improvement
Change in Percentage Visceral Fat Mass as Measured by DXA
Time frame:Baseline (Week 9) to Week 20
Visceral fat, change
percent change from baseline, improvement
Change in Body Weight (kg) from Baseline (Week 9) to Week 20
Time frame:Baseline (Week 9) to Week 20
Body weight, absolute change (kg)
change from baseline, improvement
Proportion of Participants Achieving ≥2% and ≥3% Reduction in Body Weight from Baseline (Week 9) to Week 20
Time frame:Baseline (Week 9) to Week 20
threshold achievement, improvement
Glycemic / diabetes
1 endpointChange in Glycemic Parameters from Baseline (Week 9) to Week 20
Time frame:Baseline (Week 9) to Week 20
change from baseline, improvement
componentsHbA1c, change, Fasting glucose, change
MASH / liver
7 endpointsAbsolute Change in Liver Fat Content as Measured by MRI-PDFF in Participants With Hepatic Steatosis
Time frame:Baseline (Week 9) to Week 20
Liver fat content, change
change from baseline, improvement
Percentage Change in Liver Fat Content as Measured by MRI-PDFF in Participants With Hepatic Steatosis
Time frame:Baseline (Week 9) to Week 20
Liver fat content, change
percent change from baseline, improvement
Proportion of Participants With ≥30% Relative Reduction in Liver Fat Content as Measured by MRI-PDFF
Time frame:Baseline (Week 9) to Week 20
MRI-PDFF ≥30% responders
threshold achievement, improvement
Change in Alanine Aminotransferase (ALT) Levels from Baseline (Week 9) to Week 20
Time frame:Baseline (Week 9) to Week 20
ALT, change
change from baseline, improvement
LOINC 1742-6
Change in Aspartate Aminotransferase (AST) Levels from Baseline (Week 9) to Week 20
Time frame:Baseline (Week 9) to Week 20
AST, change
change from baseline, improvement
LOINC 1920-8
Change in Alkaline Phosphatase (ALP) Levels from Baseline (Week 9) to Week 20
Time frame:Baseline (Week 9) to Week 20
change from baseline, improvement
Change in Gamma-Glutamyl Transferase (GGT) Levels from Baseline (Week 9) to Week 20
Time frame:Baseline (Week 9) to Week 20
γ-GT, change
change from baseline, improvement
Cardiometabolic biomarkers
2 endpointsChange in Lipid Parameters from Baseline (Week 9) to Week 20
Time frame:Baseline (Week 9) to Week 20
change from baseline, improvement
Changes in Vital Signs Findings
Time frame:Baseline through Week 20
change from baseline, improvement
Safety / tolerability / PK
4 endpointsFrequency of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame:From first dose through Week 20 (or end of study visit)
Treatment-emergent AEs (any)
event count, event
componentsTreatment-emergent AEs (any), Serious AEs (any)
Severity of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame:From first dose through Week 20 (or end of study visit)
Serious AEs (any)
descriptive
componentsTreatment-emergent AEs (any), Serious AEs (any)
Laboratory Safety Evaluations
Time frame:Baseline through Week 20
descriptive
Changes in 12-Lead Electrocardiogram (ECG) Parameters
Time frame:Baseline through Week 20
change from baseline, descriptive
Other (unclassified)
1 endpointChanges in Physical Examination Findings
Time frame:Baseline through Week 20
descriptive
Provenance
Sources
Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.