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Not yet recruitingPhase 1

A Trial of Oral VRB-103 Alone or in Combination With Oral Ecnoglutide (VRB-101) in Participants With Obesity or Overweight

A Randomized, Double-blind, Placebo-controlled, First-in-Human Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral VRB-103 Alone or in Combination With Oral Ecnoglutide (VRB-101) in Participants With Obesity or Overweight

Asset

Ecnoglutide

Oral · GLP-1 agonist

Listed sites

0

Recruiting sites

Enrollment

336

estimated

Study population

Obesity / overweight

Key I/E criteria

HbA1c ≤6.4%eGFR ≥60Healthy volunteers

Primary endpoints

Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)Adverse Events of Special Interest (AESIs)Columbia-Suicide Severity Rating Scale (C-SSRS)

Identifiers

Registered as

NCT IDNCT07628127
Org study IDVRB-103-101

Timeline

Milestones

Study first posted2026-06-04actual
Last update posted2026-06-04actual
Study start2026-07estimated (month precision)
Primary completion2028-03estimated (month precision)
Study completion2028-03estimated (month precision)

Assets

Investigational agents

Study populations

Who this study enrolls

Obesity / overweight

Eligibility

Who can enroll

Minimum age18 Years
Maximum age60 Years
SexAll
Healthy volunteersAccepted

Inclusion criteria

1. Male or female assigned at birth, inclusive of all gender identities.

2. Have HbA1c ≤6.4% at Screening and Day -2 eligibility confirmation.

3. Have a BMI of:

1. ≥25 kg/m^2 and ≤35.0 kg/m^2 (Part A) OR

2. ≥27 kg/m^2 and ≤40.0 kg/m^2 (Part B and Part C)

4. Weight ≥70 kg with self-reported stable body weight (≤5% body weight change) for the 3 months prior to randomization.

5. Otherwise healthy, as defined by the absence of any clinically significant, in the Investigator's opinion, active or chronic disease (e.g., Type 2 diabetes mellitus [T2DM], cardiovascular [CV] disease, cancer, and any acute or chronic illness that could pose a problem to completing the study) as determined through a comprehensive medical and surgical history, a thorough physical exam (PE) that includes vital signs, a 12-lead Electrocardiogram (ECG), hematology, blood chemistry, serology, and urinalysis. Cardiovascular (CV) risk factors, such as dyslipidemia and mild hypertension, are expected and are allowed.

6. Have an estimated glomerular filtration rate (eGFR) >60 mL/min at Screening and Day -2 eligibility confirmation, as calculated using the 2021 Chronic Kidney Disease Epidemiology (CKD-EPI) creatinine equation, with no other clinical or laboratory evidence of renal dysfunction or impairment.

7. Persons of childbearing potential must be non-pregnant and non-lactating and must agree to use study-specified contraceptive methods.

8. Have a resting BP of ≤140/90 millimeters of mercury (mmHg) at Screening and Day -2 eligibility with 2 or less hypertension-directed medications.

Exclusion criteria

1. Have any prior diagnosis of type 1 diabetes mellitus or 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 HbA1c ≤6.4% at Screening and Day -2 eligibility confirmation and is not on medication to lower glucose.

2. Have at least 1 laboratory value suggestive of diabetes at Screening and Day -2 eligibility confirmation, including 1 or more of HbA1c >6.4% (48 mmol/mol) or random glucose ≥200 mg/dL (11.1 mmol/L).

3. Have had exposure to GLP-1, glucose-dependent insulinotropic peptide (GIP), or amylin analogs within 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 product(s), to amylin analogs, to selective GLP-1 receptor agonist (RAs), or to GIP/GLP-1 or GLP-1/glucagon dual RAs.

4. Presence or history of clinically significant cardiovascular, renal, hepatic, dermatological, respiratory, neurological, psychiatric, malignant, metabolic, endocrinological, hematological, or venereal disorder, as judged by the Investigator.

5. Have a medical history of clinically significant gastric emptying abnormality (for example, severe gastroparesis or gastric outlet obstruction), chronically take drugs that directly affect gastrointestinal (GI) motility, or have a history of any clinically relevant GI diseases or symptoms of GI disorders potentially affecting interpretation of study data.

6. Have a history of hypocalcemia or ionized serum calcium below the normal range at Screening and Day -2 eligibility confirmation.

Endpoints (11)

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

Safety / tolerability / PK
9
Patient-reported / QoL
1
Other (unclassified)
1

Patient-reported / QoL

1 endpoint
Primary/protocol endpoint

Change in Patient Health Questionnaire-9 (PHQ-9) Scores from Baseline

Time frame:Screening up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20)

change from baseline, improvement

Safety / tolerability / PK

9 endpoints
Primary/protocol endpoint

Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Time frame:Screening up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20)

event count, event

Primary/protocol endpoint

Number of Participants with Adverse Events of Special Interest (AESIs)

Time frame:Screening up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20)

event count, event

Primary/protocol endpoint

Change in Columbia-Suicide Severity Rating Scale (C-SSRS) from Baseline

Time frame:Screening up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20)

change from baseline, event

Secondary/protocol endpoint

Plasma concentrations of VRB-103 and VRB-101

Time frame:Baseline up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20)

concentration, descriptive

Secondary/protocol endpoint

Maximum Observed Plasma Concentration (Cmax) for VRB-103 and VRB-101

Time frame:Baseline up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20)

concentration, descriptive

Secondary/protocol endpoint

Time to Reach Cmax (Tmax) for VRB-103 and VRB-101

Time frame:Baseline up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20)

time to event, event

Secondary/protocol endpoint

Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (AUCinf) for VRB-103 and VRB-101

Time frame:Arm 1: From Baseline up to Day 29

concentration, descriptive

Secondary/protocol endpoint

Half-life (t1/2) for VRB-103 and VRB-101

Time frame:Baseline up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20)

concentration, descriptive

Secondary/protocol endpoint

AUC Over the Dosing Interval (AUCtau) of VRB-103 and VRB-101

Time frame:Baseline up to End of Study (Arm 2: Week 10 and Arm 3: Week 20)

concentration, descriptive

Other (unclassified)

1 endpoint
Secondary/protocol endpoint/low confidence

Trough Concentration (Ctrough) of VRB-103 and VRB-101

Time frame:Baseline up to End of Study (Arm 2: Week 10 and Arm 3: Week 20)

concentration, descriptive

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2
Snapshot dateJuly 1, 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 July 1, 2026 snapshot.