RENEW-MDD- 2

RecruitingPhase 3

A Study of Brenipatide (LY3537031) in Adult Participants With Major Depressive Disorder

A Phase 3, Multicenter, Randomized, Double-Blind, Parallel-Arm Study to Investigate the Efficacy and Safety of Adjunctive Treatment With Brenipatide in Delaying Time to Relapse Compared With Placebo in Adult Participants With Major Depressive Disorder (RENEW-MDD- 2)

Lead sponsor

Eli Lilly and Company

Asset

Brenipatide

Subcutaneous · GLP-1 / GIP dual

Listed sites

170

Recruiting sites

Estimated enrollment

1,000

Study population

Mood Disorders, Psychiatric (schizophrenia / bipolar / depression)

Eligibility highlights

Primary endpoint

•Relapse Defined as the Number of Days from Randomization to Date on Which

Registered trial locations

Locations reported to ClinicalTrials.gov for this trial snapshot. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT07775300

Org study ID27364

Secondary ID2025

Secondary ID2025-522310-24-00

Secondary IDJ2S-MC-GZMIEli Lilly and Company

Timeline

Milestones

Study start2026-08-14actual

Study first posted2026-08-20actual

Last update posted2026-11-03actual

Primary completion2028-12estimated (month precision)

Study completion2029-02estimated (month precision)

Assets

Investigational agents

Brenipatide

Who this study enrolls

Mood DisordersPsychiatric (schizophrenia / bipolar / depression)

Who can enroll

Minimum age18 Years

Maximum age75 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Meet the diagnostic criteria for major depressive disorder

•Are on stable standard of care medication for major depressive disorder

•Are reliable and willing to make themselves available for the duration of the study and attend required study visits, and are willing and able to follow study procedures as required, such as

-self-inject study intervention

-store and use the provided blinded study intervention, as directed

-maintain electronic and paper study diaries, as applicable, and

-complete the required questionnaires

Exclusion criteria

•Have a lifetime history or current diagnosis of the following:

-schizophrenia spectrum or other psychotic disorder

-bipolar disorder

-borderline personality disorder, or

-any eating disorder

•Have type 1 diabetes mellitus, or a history of:

-ketoacidosis, or

-hyperosmolar state or coma.

•Evidence of moderate or severe substance or alcohol use disorder within 180 days of screening

•Are actively suicidal or deemed a significant risk for suicide

•Have participated in a clinical study and received active treatment, or unknown if they received active treatment, within 90 days or 5 half-lives (whichever is longer) before screening

Endpoints (12)

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

Other (unclassified)

Patient-reported / QoL

Weight & body composition

Safety / tolerability / PK

Other clinical outcomes

Weight & body composition

2 endpoints

Secondary/protocol endpoint

Percent Change from Baseline in Body Weight in Participants with a Baseline Body Mass Index (BMI) ≥ 25.0 kg/m^2

Time frame:Baseline, up to at least 6 months

percent change from baseline, improvement

Secondary/protocol endpoint

Percent Change from Baseline in Body Weight in Participants with a Baseline Body Mass Index (BMI) ≥25 kg/m² and on an Atypical Antipsychotic

Time frame:Baseline, up to at least 6 months

percent change from baseline, improvement

Patient-reported / QoL

3 endpoints

Secondary/protocol endpoint

Change from Baseline in Patient-Reported Outcomes Measurement Information Systems (PROMIS) Short Form

Time frame:Baseline, up to at least 6 months

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Patient Global Impression of Severity (PGI-S)

Time frame:Baseline, up to at least 6 months

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Recovering Quality of Life - 20 Items (ReQoL-20) Total Score

Time frame:Baseline, up to at least 6 months

change from baseline, improvement

Safety / tolerability / PK

2 endpoints

Secondary/protocol endpoint

Pharmacokinetic (PK): Average Steady State Plasma Concentration (Cavg) of Brenipatide

Time frame:Baseline, up to at least 6 months

concentration, descriptive

Secondary/protocol endpoint

Number of Participants with Treatment-Emergent Anti-Drug Antibodies (ADA

Time frame:Baseline up to at least 6 months

event count, event

Other clinical outcomes

1 endpoint

Primary/protocol endpoint

Time to Relapse Defined as the Number of Days from Randomization to Date on Which the Participant Meets Any Relapse Criterion of Major Depressive Disorder (MDD)

Time frame:From Randomization in Double-Blind Adjunctive Treatment to First Relapse For at Least 12 Months

time to event, event

Other (unclassified)

4 endpoints

Secondary/protocol endpoint/low confidence

Change from Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score

Time frame:Baseline, up to at least 6 months

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change from Baseline in Sheehan Disability Scale (SDS) Global Functional Impairment Score

Time frame:Baseline, up to at least 6 months

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change from Baseline in Generalized Anxiety Disorder (GAD) - 7 Total Score

Time frame:Baseline, up to at least 6 months

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change from Baseline in Patient Rated Symptom and Disease Severity

Time frame:Baseline, up to at least 6 months

change from baseline, improvement

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateNovember 5, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

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 November 5, 2026 snapshot.