A Study of Tirzepatide (LY3298176) Plus Mibavademab Compared With Tirzepatide Alone in Adult Participants With Obesity

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Study of Once-Weekly Tirzepatide Plus Mibavademab Compared With Tirzepatide Alone in Adult Participants With Obesity

The main purpose of this study is to determine if combining tirzepatide with mibavademab will result in more weight loss in adult participants than tirzepatide alone. The study will last about 74 weeks and may include up to 19 visits.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Tirzepatide; Drug: Mibavademab; Drug: Mibavademab-Placebo; Drug: Tirzepatide-Placebo

• Study Type: Interventional
• Enrollment (Actual): 392
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Gardena, California, United States, 90247
      • Velocity Clinical Research, Gardena
    • Irvine, California, United States, 92614
      • Irvine Clinical Research
    • Los Angeles, California, United States, 90017
      • Velocity Clinical Research, Los Angeles
    • North Hollywood, California, United States, 91606
      • Velocity Clinical Research, North Hollywood
    • Santa Ana, California, United States, 92704
      • Velocity Clinical Research, Santa Ana
    • Van Nuys, California, United States, 91405
      • Velocity Clinical Research, Panorama City
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Idaho
    • Meridian, Idaho, United States, 83646
      • Solaris Clinical Research
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research
    • New Orleans, Louisiana, United States, 70119
      • Velocity Clinical Research - New Orleans
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Hassman Research Institute Marlton Site
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Lillestol Research
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Research Center
  • Texas
    • Corpus Christi, Texas, United States, 78404
      • South Texas Clinical Research
    • Dallas, Texas, United States, 75230
      • Velocity Clinical Research, Dallas
    • Houston, Texas, United States, 77040
      • Juno Research
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have a body mass index (BMI) of ≥30 kilogram/square meter (kg/m²) and ≤40 kg/m²
• Willing to learn how to self-inject study intervention (visually impaired persons who are not able to perform the injections must have the assistance of a sighted individual trained to inject the study intervention; persons with physical limitations who are not able to perform the injections must have the assistance of an individual trained to inject the study intervention)
• Male or female contraceptive use by participant should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion Criteria:

• Have a history of diabetes mellitus, including Type 1 Diabetes Mellitus (T1DM) or Type 2 Diabetes Mellitus (T2DM), history of ketoacidosis, or hyperosmolar state/coma
• Have a self-reported change (increase or decrease) in body weight >5 kilogram (kg) within 3 months prior to screening
• Have a family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia (MEN) syndrome type 2
• Have acute or chronic hepatitis
• Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy for less than 5 years

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tirzepatide (TZP) + Mibavademab (MIBA) [Group A]; Participants will receive TZP subcutaneously (SC) and MIBA for 24 weeks. Participants in Group A will be randomized (Randomization 2) to groups C and D at week 24.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176; Drug: Mibavademab; Administered SC; Other Names: REGN4461
Experimental: TZP + Mibavademab-placebo (MIBA-PBO) [Group B]; Participants will receive TZP SC and MIBA-PBO SC for 24 weeks. Participants in Group B will be randomized (Randomization 2) to Groups E, F, G, and H at week 24.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176; Drug: Mibavademab-Placebo; Administered SC
Experimental: TZP + MIBA then Tirzepatide-placebo (TZP-PBO) + MIBA [Group C]; Participants will receive TZP SC and MIBA SC for 24 weeks followed by TZP-PBO SC and MIBA SC for 24 weeks.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176; Drug: Mibavademab; Administered SC; Other Names: REGN4461; Drug: Tirzepatide-Placebo; Administered SC
Experimental: TZP + MIBA-PBO [Group E]; Participants will receive TZP SC + MIBA-PBO SC for 48 weeks.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176; Drug: Mibavademab-Placebo; Administered SC
Experimental: TZP + MIBA-PBO then TZP-PBO + MIBA [Group F]; Participants will receive TZP SC + MIBA-PBO SC for 24 weeks followed by TZP-PBO SC + MIBA SC for 24 weeks.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176; Drug: Mibavademab; Administered SC; Other Names: REGN4461; Drug: Mibavademab-Placebo; Administered SC; Drug: Tirzepatide-Placebo; Administered SC
Experimental: TZP + MIBA-PBO then TZP + MIBA [Group G]; Participants will receive TZP SC + MIBA-PBO SC for 24 weeks followed by TZP SC + MIBA SC for 24 weeks.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176; Drug: Mibavademab; Administered SC; Other Names: REGN4461; Drug: Mibavademab-Placebo; Administered SC
Experimental: TZP + MIBA-PBO then TZP-PBO + MIBA-PBO [Group H]; Participants will receive TZP SC + MIBA-PBO SC for 24 weeks followed by TZP-PBO SC + MIBA-PBO SC for 24 weeks.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176; Drug: Mibavademab-Placebo; Administered SC; Drug: Tirzepatide-Placebo; Administered SC
Experimental: TZP + MIBA [Group D]; Participants will receive TZP SC + MIBA SC for 48 weeks.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176; Drug: Mibavademab; Administered SC; Other Names: REGN4461

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean Percent Change from Baseline in Body Weight	Baseline, Week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants Who Achieve ≥5% Body Weight Reduction	Baseline to Week 48
Percentage of Participants Who Achieve ≥10% Body Weight Reduction	Baseline to Week 48
Mean Change from Baseline for Percent Change and Absolute Change in Body Weight (kg)	Baseline, Week 24
Mean Absolute Change from Baseline for Body Weight (kg)	Baseline, Week 48
Percentage of Participants Who Achieve ≥15% Body Weight Reduction	Baseline to Week 48
Percentage of Participants Who Achieve ≥20 Body Weight Reduction	Baseline to Week 48
Mean Percent Change from Randomization 2 for Body Weight	Week 24, Week 48
Mean Change from Randomization 2 for Body Weight (kg)	Week 24, Week 48
Mean Absolute Change from Randomization 2 for Body Weight (kg)	Week 24, Week 48
Change from Baseline to Week 24 in CoEQ Scores	Baseline, Week 24
Change from Baseline in FCQ-T-r Scores	Baseline, Week 24
Change from Baseline in FCQ-T-r Scores	Baseline, Week 48
Change from Baseline to Week 48 in CoEQ Scores	Baseline, Week 48

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

Helpful Links

• A Study of Tirzepatide (LY3298176) Plus Mibavademab Compared With Tirzepatide Alone in Adult Participants With Obesity

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2024
• Primary Completion (Actual): December 15, 2025
• Study Completion (Actual): April 2, 2026

Study Registration Dates

• First Submitted: April 16, 2024
• First Submitted That Met QC Criteria: April 16, 2024
• First Posted (Actual): April 18, 2024

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Leptin; Weight maintenance; Incretin; Glucagon-like peptide-1 (GLP-1)
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Amino Acids, Peptides, and Proteins; Proteins; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Tirzepatide
• Other Study ID Numbers: 18750; I8F-MC-GPIV (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 and 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