A Study of Brenipatide in Participants With Opioid Use Disorder (RENEW-Op-1)

September 3, 2026 updated by: Eli Lilly and Company

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study With a Separate Open-label Cohort to Evaluate the Efficacy and Safety of Brenipatide as Adjunctive Treatment to Transmucosal Buprenorphine With or Without Naloxone in Early Recovery of Participants With Opioid Use Disorder (RENEW-Op-1)

The purpose of this study is to see if brenipatide, when compared to placebo, is safe and effective for participants with opioid use disorder, when used with buprenorphine with or without naloxone.

The maximum potential duration of study participation for a participant in Part A is approximately 144 weeks, maximum potential duration of study participation for a participant in Part B is approximately 116 weeks. The actual duration will vary for each participant depending on the time of enrollment and the overall rate of study enrollment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The study consists of 2 parts, each with its own participant cohort

  • Part A: double-blind treatment with open-label extension (OLE)
  • Part B: open-label treatment.

Participants will be enrolled in only one part of the study.

Study Type

Interventional

Enrollment (Estimated)

465

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

  • Canada
      • Calgary, Canada, T2N 4L7
        • Recruiting
        • Care Clinic
        • Contact:
          • Phone Number: 587-955-3401
        • Principal Investigator:
          • Sumantra Ghosh
      • Courtice, Canada, L1E 2J5
        • Recruiting
        • Med Trust Research
        • Principal Investigator:
          • Hamilton Jeyaraj
        • Contact:
          • Phone Number: 905-728-7915
      • Kamloops, Canada, V2C 1K7
        • Recruiting
        • The Medical Arts Health Research Group
        • Principal Investigator:
          • Dustin Janz
      • Kelowna, Canada, V1Y 5A8
        • Recruiting
        • Kelowna Health and Memory Centre
        • Principal Investigator:
          • Eugene Okorie
      • Kingston, Canada, K7L 4X3
        • Recruiting
        • Providence Care
        • Contact:
          • Phone Number: 6135444900
        • Principal Investigator:
          • Roumen Milev
      • Mississauga, Canada, L4T 4J2
        • Recruiting
        • Malton Medical Group
        • Contact:
          • Phone Number: 905-677-4200
        • Principal Investigator:
          • Brian Zidel
      • Toronto, Canada, M4J 1M3
        • Recruiting
        • Comprehensive Treatment Clinic
        • Principal Investigator:
          • Leonard Bienenstock
      • Toronto, Canada, M6J 1H4
        • Recruiting
        • Centre for Addiction and Mental Health (CAMH)
        • Principal Investigator:
          • Bernard Le Foll
  • Puerto Rico
      • Guaynabo, Puerto Rico, 00966
        • Recruiting
        • Research Works San Juan
        • Contact:
          • Phone Number: 787-315-1669
        • Principal Investigator:
          • Jose Feliberti
  • United Kingdom
      • Chertsey, United Kingdom, KT16 9AU
        • Recruiting
        • Surrey and Borders Partnership NHS Foundation Trust
        • Principal Investigator:
          • CHRISTOS KOUIMTSIDIS
      • Doncaster, United Kingdom, DN4 8QN
        • Not yet recruiting
        • Clerkenwell Health - Doncaster
        • Principal Investigator:
          • Ibreez Ajaz
      • Eastbourne, United Kingdom, BN23 5UZ
        • Not yet recruiting
        • St Pancras Clinical Research - Eastbourne
        • Contact:
          • Phone Number: 020 3865 1142
        • Principal Investigator:
          • Graham Campbell
      • Glasgow, United Kingdom, G51 4TF
        • Recruiting
        • Queen Elizabeth University Hospital
        • Contact:
          • Phone Number: (+44) 0141 232 7600
        • Principal Investigator:
          • Nagore Penades
      • London, United Kingdom, EC2Y 8EA
        • Recruiting
        • St Pancras Clinical Research
        • Contact:
          • Phone Number: 02038651142
        • Principal Investigator:
          • Ward Lawrence
      • London, United Kingdom, W1G 8DR
        • Not yet recruiting
        • Clerkenwell Health - London - Welbeck Street
        • Principal Investigator:
          • Alishah Suleman
      • London, United Kingdom, SE6 4LF
        • Recruiting
        • Bioluminux - London
        • Principal Investigator:
          • Laxmi Patel
      • Manchester, United Kingdom, M25 3BL
        • Not yet recruiting
        • Greater Manchester Mental Health NHS Foundation Trust
        • Principal Investigator:
          • Stephen Kaar
      • Milton Keynes, United Kingdom, MK15 0DU
        • Recruiting
        • Bioluminux Clinical Research - Milton Keynes
        • Principal Investigator:
          • Kayode Timothy
      • Southampton, United Kingdom, SO15 2AQ
        • Recruiting
        • Bioluminux - Southampton
        • Principal Investigator:
          • Adebayo Jejeloye
      • Uxbridge, United Kingdom, UB8 1JP
        • Not yet recruiting
        • Old Bank House Hillingdon Drug & Alcohol
        • Principal Investigator:
          • Jeffrey Fehler
      • Wolverhampton, United Kingdom, WV9 5HB
        • Recruiting
        • Bioluminux - Wolverhampton
        • Principal Investigator:
          • Joshua Olofinlade
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85028
        • Recruiting
        • NoesisPharma - Phoenix - East Shea Boulevard
        • Principal Investigator:
          • John Prater
    • Arkansas
      • Little Rock, Arkansas, United States, 72211
        • Recruiting
        • Woodland International Research Group
        • Contact:
          • Phone Number: 501-221-8681
        • Principal Investigator:
          • George Konis
      • Little Rock, Arkansas, United States, 72204
        • Recruiting
        • Pillar Clinical Research- Little Rock
        • Principal Investigator:
          • Leslie Smith
    • California
      • Fountain Valley, California, United States, 92708
        • Recruiting
        • ARK Clinical Research - Fountain Valley
        • Principal Investigator:
          • Justin Yanuck
        • Contact:
          • Phone Number: 714-988-2021
      • San Francisco, California, United States, 94102
        • Recruiting
        • Center on Substance Use and Health (CSUH)
        • Principal Investigator:
          • Phillip Coffin
      • San Francisco, California, United States, 94158
        • Recruiting
        • UCSF Weill Institute for Neurosciences - Substance Use Disorders Clinic - Mission Bay
        • Principal Investigator:
          • Khaled Moussawi
    • Florida
      • Bradenton, Florida, United States, 34205
        • Recruiting
        • Bradenton Research Center, Inc.
        • Principal Investigator:
          • Eric Folkens
        • Contact:
          • Phone Number: 941-708-0005
      • Daytona Beach, Florida, United States, 32114
        • Recruiting
        • K2 Medical Research - Daytona Beach
        • Principal Investigator:
          • Esteban Olivera
      • Hollywood, Florida, United States, 33024
        • Recruiting
        • NextPhase Research Florida - Hollywood
        • Principal Investigator:
          • Peter Ventre
      • Lakeland, Florida, United States, 33803
        • Recruiting
        • Accel Research Sites - Lakeland Clinical Research Unit
        • Contact:
          • Phone Number: 863-940-2087
        • Principal Investigator:
          • James Andersen
      • Miami, Florida, United States, 33126
        • Recruiting
        • Life Arc Research Centers - Miami
        • Contact:
          • Phone Number: 305-874-7401
        • Principal Investigator:
          • Janny Rivera
      • Naples, Florida, United States, 34102
        • Recruiting
        • Advanced Research for Health Improvement, LLC
        • Contact:
          • Phone Number: 239-230-2021
        • Principal Investigator:
          • Leonard Lado
      • Port Charlotte, Florida, United States, 33952
        • Recruiting
        • Innovative Research Institute - Port Charlotte
        • Principal Investigator:
          • Joseph Ravid
        • Contact:
          • Phone Number: 941-505-2100
      • Tampa, Florida, United States, 33614
        • Recruiting
        • Better Years Ahead Medical Center
        • Principal Investigator:
          • Ana Suarez
        • Contact:
          • Phone Number: 813-709-8299
      • West Palm Beach, Florida, United States, 33407
        • Recruiting
        • Neuroscience Research Institute - West Palm Beach
        • Principal Investigator:
          • Danesh Alam
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Re:Cognition Health - Chicago
        • Principal Investigator:
          • Abid Nazeer
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Indiana University Health Neuroscience Center
        • Principal Investigator:
          • Michael Bushey
    • Kentucky
      • Lexington, Kentucky, United States, 40508
        • Recruiting
        • University of Kentucky Chandler Medical Center
        • Principal Investigator:
          • Shanna Babalonis
    • Maryland
      • Baltimore, Maryland, United States, 21229
        • Recruiting
        • Maryland Treatment Centers - Mountain Manor Treatment Center
        • Principal Investigator:
          • Marc Fishman
      • Rockville, Maryland, United States, 20853
        • Recruiting
        • Maryland Treatment Centers - Avery Road Treatment Center
        • Principal Investigator:
          • Marc Fishman
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Brigham and Women's Hospital
        • Principal Investigator:
          • Joji Suzuki
      • Boston, Massachusetts, United States, 02118
        • Not yet recruiting
        • Boston Medical Center
        • Principal Investigator:
          • Alyssa Peterkin
      • Boston, Massachusetts, United States, 02116
        • Recruiting
        • Adams Clinical Boston
        • Principal Investigator:
          • Darin Dougherty
      • Watertown, Massachusetts, United States, 02472
        • Recruiting
        • Adams Clinical Watertown
        • Contact:
          • Phone Number: 617-744-8542
        • Principal Investigator:
          • Daniel Rutrick
    • Mississippi
      • Ridgeland, Mississippi, United States, 39157
        • Recruiting
        • SKY Integrative Medical Center/SKYCRNG
        • Principal Investigator:
          • Bob Hutchins
        • Contact:
          • Phone Number: 601-567-1321
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • Adams Clinical Harlem
        • Principal Investigator:
          • Rachel Noone
        • Contact:
          • Phone Number: 917-423-67697
      • The Bronx, New York, United States, 10461
        • Recruiting
        • Adams Clinical Bronx
        • Principal Investigator:
          • Shama Farooq
    • Ohio
      • Columbus, Ohio, United States, 43212
        • Recruiting
        • Ohio Clinical Trials
        • Contact:
          • Phone Number: 380-210-2424
        • Principal Investigator:
          • Angela Eakin
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73112
        • Not yet recruiting
        • Rivus Wellness and Research Institute
        • Principal Investigator:
          • Marvin Peyton
        • Contact:
          • Phone Number: 405-753-4994
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Penn Medicine: University of Pennsylvania Health System
        • Principal Investigator:
          • Kyle Kampman
        • Contact:
          • Phone Number: 610-639-3592
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Adams Clinical Philadelphia
        • Principal Investigator:
          • Cassie Blanchard
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Recruiting
        • Brown University School of Public Health
        • Principal Investigator:
          • Carolina Haass-Koffler
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57108
        • Recruiting
        • Avera Research Institute - Sioux Falls
        • Contact:
          • Phone Number: 605-504-3154
        • Principal Investigator:
          • Vivek Anand
    • Texas
      • DeSoto, Texas, United States, 75115
        • Recruiting
        • Adams Clinical Dallas
        • Principal Investigator:
          • Benji Kurian
      • Houston, Texas, United States, 77043
        • Recruiting
        • Biopharma Informatic, LLC
        • Contact:
          • Phone Number: 281-944-3610
        • Principal Investigator:
          • James Lai, MD
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • Not yet recruiting
        • University of Virginia Health System
        • Contact:
          • Phone Number: 434-243-0563
        • Principal Investigator:
          • Nassima Ait-Daoud Tiouririne
      • Roanoke, Virginia, United States, 24014
        • Recruiting
        • Carilion Clinic
        • Contact:
          • Phone Number: 540-981-8025
        • Principal Investigator:
          • Albert Arias
    • Washington
      • Seattle, Washington, United States, 98104
        • Recruiting
        • University of Washington - Harborview Medical Center
        • Principal Investigator:
          • Elenore Bhatraju

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Have a current mild, moderate or severe opioid use disorder (OUD)

  • Are reliable and willing to make themselves available for the duration of the study (for example, are not incarcerated, not homeless) and attend required study visits, and are willing and able to follow study procedures as required, such as

    • self-inject study intervention Note: Participants who are not able to perform the injections must have the assistance of a support person trained to administer the study intervention
    • store and use the provided study intervention as directed
    • maintain electronic or paper study diaries, as applicable, and
    • complete the required questionnaires
  • Are intermittently using non-legal, non-prescribed opioids
  • Are taking buprenorphine for treatment on OUD

Exclusion Criteria:

  • Evidence of other substance use disorder(s) within 180 days of screening, except the following are permitted: any level tobacco use disorder, mild-to-moderate alcohol or mild-to-moderate cannabis use disorder

Note: any level of caffeine use is allowed

  • Are actively suicidal or deemed a significant risk for suicide
  • Have a history of advanced liver disease (including advanced liver fibrosis or cirrhosis or alcohol-associated hepatitis based on either prior liver histology or imaging studies, such as transient elastography, ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI), or Enhanced Liver Fibrosis score
  • 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
  • Had opioid overdose in past 6 months prior to screening

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

    • schizophrenia or other psychotic disorder
    • bipolar disorder
    • borderline personality disorder
    • any eating disorder
  • Have type 1 diabetes mellitus, or a history of ketoacidosis, or hyperosmolar state, or coma

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: Part A and Part B: Brenipatide + Buprenorphine Dose 1

Part A: Brenipatide administered subcutaneously (SC) + Buprenorphine administered sublingual or buccal.

Part B: Open-label Treatment: Participants will receive Brenipatide SC + Buprenorphine sublingual or buccal.
Drug: Brenipatide
Administered SC
Other Names:
  • LY3537031
Drug: Buprenorphine
Administered sublingual or buccal
Experimental: Part A: Brenipatide + Buprenorphine Dose 2
Brenipatide administered SC + Buprenorphine administered sublingual or buccal.
Drug: Brenipatide
Administered SC
Other Names:
  • LY3537031
Drug: Buprenorphine
Administered sublingual or buccal
Experimental: Part A: Brenipatide + Buprenorphine Dose 3
Brenipatide administered SC + Buprenorphine administered sublingual or buccal.
Drug: Brenipatide
Administered SC
Other Names:
  • LY3537031
Drug: Buprenorphine
Administered sublingual or buccal
Placebo Comparator: Part A: Placebo + Buprenorphine
Placebo administered SC + Buprenorphine administered sublingual or buccal.
Drug: Placebo
Administered SC
Drug: Buprenorphine
Administered sublingual or buccal

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percentage of Weeks of Abstinence from Opioid Use Defined by Both Negative Urine Drug Screen (UDS) and no Self-Report of Opioid use Based on Timeline Followback (TLFB)
Time Frame: Week 13 up to Week 24
Week 13 up to Week 24
Achievement of ≥80% Weeks of Abstinence from Opioid Use Defined by Both Negative UDS and no Self-Report of Opioid Use Based on TLFB
Time Frame: Week 13 up to Week 24
Week 13 up to Week 24

Secondary Outcome Measures

Outcome Measure
Time Frame
Change from Baseline in Body Weight
Time Frame: Baseline, Week 24
Baseline, Week 24
Change from Baseline in Body Mass Index (BMI)
Time Frame: Baseline, Week 24
Baseline, Week 24
Gated Secondary Outcome: Adherence to Buprenorphine as Demonstrated by Self-Report Buprenorphine, with or Without Naloxone (BUP±NX) and not Contradicted by Negative UDS (BUP)
Time Frame: Week 13 up to Week 24
Week 13 up to Week 24
Achievement of 100% Weeks of Abstinence from Opioid Use Defined by Both Negative UDS and no Self-Report of Opioid Use Based on TLFB
Time Frame: Week 13 up to Week 24
Week 13 up to Week 24
Occurrence of Opioid Overdose(s) (Nonfatal or Fatal)
Time Frame: Week 1 up to Week 24
Week 1 up to Week 24
Change in Buprenorphine Dose From Baseline
Time Frame: Baseline, Week 24
Baseline, Week 24
Change from Baseline in Modified Penn Craving Scale (PCS)
Time Frame: Baseline, Week 24
Baseline, Week 24
Change from Baseline on Incidence of Healthcare Provider Visits Using Lilly-developed Health Care Resource Utilization (HCRU) scale
Time Frame: Baseline, Week 24
Baseline, Week 24
Change from Baseline on Work and Social Adjustment Scale (WSAS)
Time Frame: Baseline, Week 24
Baseline, Week 24
Achievement of >1 Level of Reduction of Diagnosis Severity Category or no Longer Have OUD Diagnosis per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
Time Frame: Baseline, Week 24
Baseline, Week 24
Change from Baseline on Quality of Life Outcome on Short Inventory of Problems - Revised (SIP-R)
Time Frame: Baseline, Week 24
Baseline, Week 24
Change from Baseline in Blood Pressure
Time Frame: Baseline, Week 24
Baseline, Week 24
Pharmacokinetics (PK): Average Steady State Plasma Concentration (Cavg) of Brenipatide
Time Frame: Baseline up to Week 24
Baseline up to Week 24
Number of Participants with Treatment-Emergent Anti-drug Antibodies
Time Frame: Baseline up to Week 24
Baseline up to Week 24

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

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 (Actual)

February 13, 2026

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

March 1, 2028

Study Registration Dates

First Submitted

February 11, 2026

First Submitted That Met QC Criteria

February 18, 2026

First Posted (Actual)

February 19, 2026

Study Record Updates

Last Update Posted (Actual)

September 4, 2026

Last Update Submitted That Met QC Criteria

September 3, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 27348
  • J2S-MC-GZMG (Other Identifier: Eli Lilly and Company)

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 EU, whichever is later. Data will be indefinitely available for requesting.

IPD Sharing Access Criteria

A research proposal should be approved by an independent review panel and researchers should 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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