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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
Lead sponsor
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 ≥60•Healthy 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
Timeline
Milestones
Assets
Investigational agents
Study populations
Who this study enrolls
Eligibility
Who can enroll
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
Patient-reported / QoL
1 endpointChange 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 endpointsNumber 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
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
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
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
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
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
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
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
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 endpointTrough 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 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.