A Study of Brenipatide in Participants With Major Depressive Disorder (RENEW-MDD-3)

November 5, 2026 updated by: Eli Lilly and Company

A Phase 2, Multicenter, Randomized, Double-blind, Parallel-arm Study to Investigate the Efficacy and Safety of Adjunctive Treatment With Brenipatide Compared With Placebo in Adult Participants With Major Depressive Disorder Who Have Partial Response to Antidepressant Therapy (RENEW-MDD-3)

This study evaluates the safety and efficacy of brenipatide (LY3537031) as an add on therapy in participants with major depression who still have symptoms while taking a stable dose of standard of care anti-depressant medicine.

The study will last approximately 5 months.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

330

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
  • Phone Number: 1-317-615-4559
  • Email: LillyTrials@Lilly.com

Study Contact Backup

Study Locations

  • Bulgaria
      • Pleven, Bulgaria, 5800
        • UMHAT Dr Georgi Stranski
        • Principal Investigator:
          • Maya Stoimenova-Popova
      • Plovdiv, Bulgaria, 4004
        • Medical Center MentalCare
        • Principal Investigator:
          • Stanka Yazova
      • Sofia, Bulgaria, 1000
        • Mental Health Center - Sofia EOOD
        • Principal Investigator:
          • Emil Grashnov
      • Varna, Bulgaria, 9020
        • DCC Mladost-M Varna OOD
        • Principal Investigator:
          • Hristo Kozhuharov
      • Vratsa, Bulgaria, 3001
        • Mental Health Center - Vratsa
        • Principal Investigator:
          • Nadya Ivanova
  • Hungary
      • Budapest, Hungary, 1033
        • Clinexpert Gyöngyös
        • Principal Investigator:
          • Tiberiu Dina
      • Gyöngyös, Hungary, 3200
        • Clinexpert Gyöngyös
        • Principal Investigator:
          • Anita Kiss
  • Netherlands
      • 's-Hertogenbosch, Netherlands, 5223 LA
        • Brain Research Center Den Bosch B.V.
        • Principal Investigator:
          • Roel Mocking
      • Amsterdam, Netherlands, 1081 GM
        • Alzheimer's Research Center
        • Principal Investigator:
          • Roel Mocking
      • Groningen, Netherlands, 9700 RB
        • University Medical Center Groningen
        • Principal Investigator:
          • Robert Schoevers
      • Leiden, Netherlands, 2333 ZA
        • Leids Universitair Medisch Centrum
        • Principal Investigator:
          • Nic van der Wee
      • Zwolle, Netherlands, 8025 AZ
        • Brain Research Center Zwolle
        • Principal Investigator:
          • Roel Mocking
  • Poland
      • Bialystok, Poland, 15-404
        • MłynowaMed Specialist Psychiatric Medical Practice Joanna Łazarczyk
        • Principal Investigator:
          • Joanna Lazarczyk
      • Bialystok, Poland, 15-464
        • Wlokiennicza Praktyka Lekarska dr n. med. Tomasz Markowski
        • Principal Investigator:
          • Tomasz Markowski
      • Bydgoszcz, Poland, 85-133
        • Promente - Center of Neurology and Psychogeriatrics
        • Principal Investigator:
          • Katarzyna Lachut
      • Gdansk, Poland, 80-211
        • Gdanski Uniwersytet Medyczny
        • Principal Investigator:
          • Karol Grabowski
      • Gdansk, Poland, 80-546
        • Penta Hospitals Badania Kliniczne - Gdańsk 1
        • Principal Investigator:
          • Katarzyna Binkowska-Michalik
      • Lodz, Poland, 91 495
        • AmiCare Sp. z o.o. Sp. K.
        • Principal Investigator:
          • Katarzyna Przybyłowska- Kustosik
      • Lublin, Poland, 20-064
        • Instytut Naukowo-Badawczy w Lublinie Sp. z o.o.
        • Principal Investigator:
          • Grzegorz Opielak
      • Olkusz, Poland, 32-300
        • Nowy Szpital w Olkuszu
        • Principal Investigator:
          • Katarzyna Urbańczyk-Łosień
      • Rybnik, Poland, 44-200
        • M2M Med Badania Sp. Z o.o
        • Principal Investigator:
          • Wojciech Eysymontt
      • Suchy Las, Poland, 62-002
        • Indywidualna Specjalistyczna Praktyka Lekarska Agnieszka Remlinger-Molenda
        • Principal Investigator:
          • Agnieszka Remlinger
      • Warsaw, Poland, 02-957
        • IPIN Warsaw - Instytut Psychiatrii i Neurologii w Warszawie (IPIN)
        • Principal Investigator:
          • Adam Wichniak
  • Romania
      • Bragadiru, Romania, 077025
        • Ames Research Center S.R.L.
        • Principal Investigator:
          • Dan Rosu
      • Bucharest, Romania, 41914
        • Prof. Dr. Alexandru Obregia Psychiatry Hospital
        • Principal Investigator:
          • Adela Ciobanu
      • Bucharest, Romania, 031441
        • Futuremeds - București
        • Principal Investigator:
          • Alexandru Pavel
      • Bucharest, Romania, 020744
        • Clinic Nutrimed Cercetare S.R.L.
        • Principal Investigator:
          • Marian Onofreiu
      • Galati, Romania, 800179
        • Spitalul De Psihiatrie Elisabeta- Domna- Galati
        • Principal Investigator:
          • Claudiu Ionut Vasile
      • Galati, Romania, 800183
        • FutureMeds SRL - Galati
        • Principal Investigator:
          • Mihai Mutica
  • Spain
      • Alcorcón, Spain, 28922
        • Hospital Fundación Alcorcón
        • Principal Investigator:
          • Francisco Montanes Rada
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
        • Principal Investigator:
          • Josep-Antoni Ramos-Quiroga
      • Madrid, Spain, 28022
        • Clinica Universidad Navarra-Sede Madrid
        • Principal Investigator:
          • Patricio Molero Santos
      • Salamanca, Spain, 37007
        • Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca
        • Principal Investigator:
          • ANGEL MONTEJO
      • Valdemoro, Spain, 28342
        • Hospital Universitario Infanta Elena
        • Principal Investigator:
          • Enrique Baca-Garcia
      • Vigo, Spain, 36213
        • Hospital Álvaro Cunqueiro
        • Principal Investigator:
          • Jose Antonio Campos Perez
      • Zamora, Spain, 49022
        • Hospital Virgen De La Concha
        • Principal Investigator:
          • Juan Antonio Mellado
  • United Kingdom
      • Doncaster, United Kingdom, DN4 8QN
        • Clerkenwell Health - Doncaster
        • Principal Investigator:
          • Ibreez Ajaz
      • Exeter, United Kingdom, EX2 5AF
        • Devon Partnership Trust
        • Principal Investigator:
          • Merryn Anderson
      • London, United Kingdom, W1U 6RP
        • Clerkenwell Health - London - Baker Street
        • Principal Investigator:
          • Alishah Suleman
      • London, United Kingdom, SE5 8AZ
        • The Maudsley Hospital
        • Principal Investigator:
          • Mario Juruena
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85012
        • IMA Clinical Research - Phoenix
        • Principal Investigator:
          • Payam Sadr
    • California
      • Chino, California, United States, 91710
        • Inland Psychiatric Medical Group
        • Principal Investigator:
          • Nandita Puchakayala
      • Montclair, California, United States, 91763
        • Catalina Research Institute, LLC
        • Principal Investigator:
          • Stephen Volk
      • Oceanside, California, United States, 92056
        • Excell Research
        • Principal Investigator:
          • Sherry Soefje
      • Sherman Oaks, California, United States, 91403
        • California Neuroscience Research Medical Group, Inc.
        • Principal Investigator:
          • Iman Parhami
      • West Hills, California, United States, 91307
        • Alliance Clinical West Hills
        • Principal Investigator:
          • Clifford Feldman
    • Florida
      • Hollywood, Florida, United States, 33021-6758
        • The Medici Medical Research
        • Principal Investigator:
          • Yesenia Kuan
      • Hollywood, Florida, United States, 33024
        • Research Centers of America, LLC-Hollywood
        • Principal Investigator:
          • Edwin Gomez
      • Jacksonville, Florida, United States, 32256
        • Clinical Neuroscience Solutions, Inc. dba CNS Healthcare
        • Principal Investigator:
          • Nandita Jones
      • Orlando, Florida, United States, 32807
        • Combined Research Orlando Phase I-IV LLC
        • Principal Investigator:
          • Eric Carbonell
      • Plant City, Florida, United States, 33563
        • Denali Health - Plant City, FL
        • Principal Investigator:
          • Walid Aziz
      • Tampa, Florida, United States, 33613
        • ForCare Clinical Research
        • Principal Investigator:
          • Marlene Hart
      • West Palm Beach, Florida, United States, 33407
        • Neuroscience Research Institute - West Palm Beach
        • Principal Investigator:
          • Danesh Alam
    • Georgia
      • Atlanta, Georgia, United States, 30331
        • Atlanta Center for Medical Research
        • Principal Investigator:
          • Elyssa Barron
      • Atlanta, Georgia, United States, 30328
        • Synexus Clinical Research
        • Principal Investigator:
          • Bethany Davis
      • Decatur, Georgia, United States, 30030
        • CenExel iResearch, LLC
        • Principal Investigator:
          • Saundra Maass Robinson
      • Savannah, Georgia, United States, 31405
        • CenExel iResearch, LLC
        • Principal Investigator:
          • Michael Mobley
    • Massachusetts
      • Boston, Massachusetts, United States, 02131
        • Boston Clinical Trials
        • Principal Investigator:
          • Irina Mezhebovsky
      • Boston, Massachusetts, United States, 02116
        • Adams Clinical Boston
        • Principal Investigator:
          • Darin Dougherty
      • Watertown, Massachusetts, United States, 02472
        • Adams Clinical
        • Principal Investigator:
          • Stephanie Ellickson
    • Nevada
      • Las Vegas, Nevada, United States, 89102
        • IMA Clinical Research Las Vegas
        • Principal Investigator:
          • Mustafa Rawaf
    • New Jersey
      • Marlton, New Jersey, United States, 08053
        • Hassman Research Institute Marlton Site
        • Principal Investigator:
          • Elan Cohen
      • Toms River, New Jersey, United States, 08755
        • Bio Behavioral Health
        • Principal Investigator:
          • Ashok Patel
    • New York
      • Cedarhurst, New York, United States, 11516
        • Neurobehavioral Research Inc
        • Principal Investigator:
          • Ronald Brenner
      • Mount Kisco, New York, United States, 10128
        • Bioscience Research, LLC
        • Principal Investigator:
          • David Krakow
      • New York, New York, United States, 10029
        • Adams Clinical Harlem
        • Principal Investigator:
          • Rachel Noone
      • New York, New York, United States, 10036
        • IMA Clinical Research NYC Midtown
        • Principal Investigator:
          • Eli Shalenberg
      • Staten Island, New York, United States, 10314
        • Richmond Behavioral Associates
        • Principal Investigator:
          • Adam Smith
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Lehigh Center for Clinical Research
        • Principal Investigator:
          • Paul Gross
      • Philadelphia, Pennsylvania, United States, 19104
        • Adams Clinical Philadelphia
        • Principal Investigator:
          • Cassie Blanchard
    • Texas
      • Austin, Texas, United States, 78731
        • IMA Clinical Research Austin - Northland
        • Principal Investigator:
          • Charles Sweet
      • Dallas, Texas, United States, 75243
        • Lonestar Clinical Research
        • Principal Investigator:
          • Lili Meisamy
      • DeSoto, Texas, United States, 75115
        • Adams Clinical Dallas
        • Principal Investigator:
          • Benji Kurian
    • Virginia
      • Fairfax, Virginia, United States, 22030
        • Inspire Behavioral Health
        • Principal Investigator:
          • Bhagwan Bahroo
    • Washington
      • Bellevue, Washington, United States, 98007
        • Northwest Clinical Research Center
        • Principal Investigator:
          • Wisam Al jumaili

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Have a diagnosis of Major Depressive Disorder (MDD) and are in a current major depressive episode, without psychotic features

  • Are on a stable antidepressant monotherapy regimen for the current major depressive episode

  • Are a partial responder to the current antidepressant monotherapy regimen

  • 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 or other psychotic disorder
    • bipolar disorder
    • borderline personality disorder
    • other personality disorders that would interfere with compliance with the study protocol
    • neurocognitive disorders or intellectual disability, or
    • any eating disorder

  • Have type 1 diabetes mellitus, or a history of

    • ketoacidosis, or
    • hyperosmolar state or coma

  • Have had a history of any substance or alcohol use disorder of any severity within 180 days before Visit 1

  • 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 Visit 1

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Brenipatide

Brenipatide administered subcutaneously (SC) + standard of care (SoC) anti-depressant
Drug: Brenipatide

Administered SC

Other Names:
  • LY3537031
Placebo Comparator: Placebo

Placebo administered SC + SoC anti-depressant
Drug: Placebo

Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS-9) Score
Time Frame: Baseline, Week 10
Baseline, Week 10

Secondary Outcome Measures

Outcome Measure
Time Frame
Change from Baseline in Hamilton Depression Rating Scale Score
Time Frame: Baseline, Week 10
Baseline, Week 10
Change from Baseline in Sheehan Disability Scale (SDS) Global Functional Impairment Score
Time Frame: Baseline, Week 10
Baseline, Week 10
Achievement of Body Weight Reduction ≥5% in Participants with a Baseline Body Mass Index (BMI) ≥25 kg/m²
Time Frame: Baseline, Week 10
Baseline, Week 10
Number of Participants with Treatment-Emergent Anti-Drug Antibodies (ADA)
Time Frame: Baseline, Up to Week 18
Baseline, Up to Week 18

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eli Lilly and Company

Investigators

  • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

November 1, 2026

Primary Completion (Estimated)

May 1, 2028

Study Completion (Estimated)

July 1, 2028

Study Registration Dates

First Submitted

November 5, 2026

First Submitted That Met QC Criteria

November 5, 2026

First Posted (Actual)

November 10, 2026

Study Record Updates

Last Update Posted (Actual)

November 10, 2026

Last Update Submitted That Met QC Criteria

November 5, 2026

Last Verified

November 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 27873
  • J2S-MC-GZMW (Other Identifier: Eli Lilly and Company)
  • 2026-527689-65-00 (Other Identifier: EU Trial (CTIS) Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

IPD Sharing Time Frame

Data are available 6 months after the primary publication or approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.

IPD Sharing Access Criteria

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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