A Study of Weekly Oral Ecnoglutide (VRB-101) in Participants Who Have Obesity or Overweight With Weight-Related Comorbidities (EVOLVE-2)

June 1, 2026 updated by: Verdiva Bio Dev Limited

A Randomized, Double-Blind, Placebo-Controlled Phase 2b Study of Weekly Oral Ecnoglutide (VRB-101) in Participants Who Have Obesity or Overweight With Weight-Related Comorbidities

The aim of this study is to evaluate the efficacy of VRB-101 for body weight reduction compared to placebo in participants who have obesity or overweight with weight-related comorbidities.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a randomized, double-blind, placebo-controlled study of oral ecnoglutide (VRB-101), with 5 active arms and 1 placebo arm. The study will include a Screening Period of 4 weeks, followed by a 20-week Study Treatment Period and a 4-week Safety Follow-up Period prior to the end of study (EOS) visit.

Study Type

Interventional

Enrollment (Actual)

206

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 Locations

  • United States
    • Alabama
      • Anniston, Alabama, United States, 36207
        • Clinical Study Site 103
      • Cullman, Alabama, United States, 35055
        • Clinical Study Site 109
    • Arizona
      • Phoenix, Arizona, United States, 85028
        • Clinical Study Site 110
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Clinical Study Site 113
    • California
      • Anaheim, California, United States, 92801
        • Clinical Study Site 111
      • Montclair, California, United States, 91763
        • Clinical Study Site 107
      • Tarzana, California, United States, 91356
        • Clinical Study Site 118
    • Georgia
      • Decatur, Georgia, United States, 30030
        • Clinical Study Site 119
    • Iowa
      • West Des Moines, Iowa, United States, 50266
        • Clinical Study Site 116
    • Kansas
      • Wichita, Kansas, United States, 67207
        • Clinical Study Site 106
    • Michigan
      • Southfield, Michigan, United States, 48076
        • Clinical Study Site 122
    • Nebraska
      • Omaha, Nebraska, United States, 68134
        • Clinical Study Site 121
    • New York
      • Binghamton, New York, United States, 13905
        • Clinical Study Site 117
      • Rochester, New York, United States, 14609
        • Clinical Study Site 101
    • North Carolina
      • Charlotte, North Carolina, United States, 28210
        • Clinical Study Site 120
      • Monroe, North Carolina, United States, 28112
        • Clinical Study Site 108
    • Oklahoma
      • Norman, Oklahoma, United States, 73069
        • Clinical Study Site 105
    • Pennsylvania
      • Duncansville, Pennsylvania, United States, 16635
        • Clinical Study Site 114
    • Tennessee
      • Knoxville, Tennessee, United States, 37909
        • Clinical Study Site 115
    • Texas
      • Dallas, Texas, United States, 75251
        • Clinical Study Site 112
      • San Antonio, Texas, United States, 78229
        • Clinical Study Site 102
      • San Antonio, Texas, United States, 78240
        • Clinical Study Site 104

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 hemoglobin A1c (HbA1c) <6.5%.
  • Have a BMI of ≥30 kg/m2 OR ≥27 kg/m2 and <30 kg/m2 with at least 1 weight-related comorbidity.
  • Have a self-reported history of stable body weight for the 3 months prior to randomization (≤5% body weight change).
  • Participants of childbearing potential must be non-pregnant and non-lactating and must agree to use study-specified contraceptive methods.

Exclusion Criteria:

  • Have any prior diagnosis of type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM), or other forms of diabetes mellitus. A participant with a history of gestational diabetes may be included in the study if the participant has an HbA1c < 6.5% at Screening.
  • Have at least 1 laboratory value suggestive of diabetes during Screening, including 1 or more of HbA1c ≥6.5% (48 mmol/mol) or random glucose ≥200 mg/dL (11.1 mmol/L).
  • Have had exposure to glucagon-like peptide -1 (GLP-1) 6 months prior to Screening or any prior history of known or suspected hypersensitivity/allergies, intolerability, or lack of efficacy to these medications. Have known or suspected hypersensitivity to study intervention(s), to selective GLP-1 receptor agonist (RA) or glucose-dependent insulinotropic peptide (GIP)/GLP-1 or GLP-1/glucagon (GCG) dual receptor agonists.
  • Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time within the dosing period, including follow -up, and for at least 60 days after the last dose of study intervention.

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: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Schedule A: VRB-101 (Active Arm 1)
Participants will receive VRB-101 once every week.
Drug: VRB-101
VRB-101 tablets will be administered orally.
Other Names:
  • Oral Ecnoglutide
Experimental: Schedule A: VRB-101 (Active Arm 2)
Participants will receive VRB-101 once every week.
Drug: VRB-101
VRB-101 tablets will be administered orally.
Other Names:
  • Oral Ecnoglutide
Experimental: Schedule A: VRB-101 (Active Arm 3)
Participants will receive VRB-101 once every week.
Drug: VRB-101
VRB-101 tablets will be administered orally.
Other Names:
  • Oral Ecnoglutide
Experimental: Schedule B: VRB-101 (Active Arm 4)
Participants will receive VRB-101 once every week.
Drug: VRB-101
VRB-101 tablets will be administered orally.
Other Names:
  • Oral Ecnoglutide
Experimental: Schedule B: VRB-101 (Active Arm 5)
Participants will receive VRB-101 once every week.
Drug: VRB-101
VRB-101 tablets will be administered orally.
Other Names:
  • Oral Ecnoglutide
Placebo Comparator: Pooled Placebo
Participants will receive matching placebo to VRB-101 once every week.
Drug: Placebo
Placebo tablets will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean percent change from baseline in body weight
Time Frame: From Baseline (Day 0) up to Week 21
To evaluate the efficacy of VRB-101 for body weight reduction compared to placebo in Schedule A dose regimens.
From Baseline (Day 0) up to Week 21

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Absolute change from baseline in body weight
Time Frame: From Baseline (Day 0) up to Week 21
To compare the effect of VRB-101 versus placebo on body weight in Schedule A.
From Baseline (Day 0) up to Week 21
Percentage of participants who achieve 5% or more body weight reduction
Time Frame: From Baseline (Day 0) up to Week 21
To compare the effect of VRB-101 versus placebo on body weight in Schedule A
From Baseline (Day 0) up to Week 21
Change from baseline in body mass index (BMI)
Time Frame: From Baseline (Day 0) up to Week 21
To compare the effect of VRB-101 versus placebo on body weight in Schedule A.
From Baseline (Day 0) up to Week 21
Number of study participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
Time Frame: From Baseline (Day 0) up to Week 24
To assess safety and tolerability of study interventions. Adverse events (AEs) reported after first administration of study intervention will be designated as a TEAE.
From Baseline (Day 0) up to Week 24
Change from baseline in blood pressure (BP)
Time Frame: From Baseline (Day 0) up to Week 24
To assess safety and tolerability of study interventions.
From Baseline (Day 0) up to Week 24
Change from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)
Time Frame: From Baseline (Day 0) up to Week 21
The C-SSRS systematically assesses suicidal ideation and behavior using yes/no questions, ordinal severity ratings (0-5), and intensity subscales. Results at End of Study will be compared to Baseline.
From Baseline (Day 0) up to Week 21

Collaborators and Investigators

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

Sponsor

Verdiva Bio Dev Limited

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)

November 25, 2025

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

August 1, 2026

Study Registration Dates

First Submitted

December 4, 2025

First Submitted That Met QC Criteria

December 4, 2025

First Posted (Actual)

December 15, 2025

Study Record Updates

Last Update Posted (Actual)

June 3, 2026

Last Update Submitted That Met QC Criteria

June 1, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VRB-101-201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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