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

The primary objective is to evaluate the safety and tolerability of VRB-103 tablets administered as monotherapy or VRB-103 tablets administered in combination with oral ecnoglutide tablets (VRB-101 tablets) in a single-dose regimen or in a multiple dose regimen.

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity; Overweight
• Intervention / Treatment: Drug: VRB-101; Drug: VRB-103; Other: Placebo

Detailed Description

For Arm 1 (single ascending dose [SAD] part), the primary objective is to evaluate the safety and tolerability of VRB-103 tablets administered as monotherapy or VRB-103 tablets administered in combination with oral ecnoglutide tablets (VRB-101 tablets) in a single-dose regimen to participants with elevated body mass index (BMI) (≥25 kg/m^2 and ≤35 kg/m^2) who are otherwise healthy. For Arm 2 and Arm 3 (multiple ascending dose [MAD] parts), the primary objective is to evaluate the safety and tolerability of multiple ascending doses of VRB-103 tablets administered as monotherapy, VRB-101 tablets administered as monotherapy, or VRB-103 tablets administered in combination with VRB-101 tablets to participants with elevated BMI (≥27 kg/m^2 and ≤40 kg/m^2) who are otherwise healthy.

• Study Type: Interventional
• Enrollment (Estimated): 336
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Verdiva Bio Medical Affairs; Email: medical.affairs@verdivabio.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1, SAD: VRB-103 or VRB-101 or Placebo; Each participant will receive a single oral dose of VRB-103 alone, VRB-103 co-administered with VRB-101, or placebo once.	Drug: VRB-101; VRB-101 tablets will be administered orally.; Other Names: Oral Ecnoglutide; Drug: VRB-103; VRB-103 tablets will be administered orally.; Other: Placebo; Placebo tablets will be administered orally.
Experimental: Arm 2, MAD: VRB-103 or VRB-101 or Placebo; Each participant will receive oral doses of VRB-103 alone, VRB-101 alone, VRB-103 co-administered with VRB-101, or placebo, once weekly or once daily.	Drug: VRB-101; VRB-101 tablets will be administered orally.; Other Names: Oral Ecnoglutide; Drug: VRB-103; VRB-103 tablets will be administered orally.; Other: Placebo; Placebo tablets will be administered orally.
Experimental: Arm 3, MAD: VRB-103 or VRB-101 or Placebo; Each participant will receive oral doses of VRB-103 alone, VRB-101 alone, VRB-103 co-administered with VRB-101, or placebo, once weekly.	Drug: VRB-101; VRB-101 tablets will be administered orally.; Other Names: Oral Ecnoglutide; Drug: VRB-103; VRB-103 tablets will be administered orally.; Other: Placebo; Placebo tablets will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Any clinically significant changes in lab parameters, hematology, ECG parameters, will be reported as TEAEs.	Screening up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20)
Number of Participants with Adverse Events of Special Interest (AESIs)		Screening up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20)
Change in Columbia-Suicide Severity Rating Scale (C-SSRS) from Baseline	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.	Screening up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20)
Change in Patient Health Questionnaire-9 (PHQ-9) Scores from Baseline	The PHQ-9 is a 9-item validated assessment, measures the severity of depression. Each item is rated from 0 to 3, for a total score out of 27. A score of 15-19 indicates moderately severe depression, and a score of 20-27 indicates severe depression.	Screening up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20)

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma concentrations of VRB-103 and VRB-101	Baseline up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20)
Maximum Observed Plasma Concentration (Cmax) for VRB-103 and VRB-101	Baseline up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20)
Time to Reach Cmax (Tmax) for VRB-103 and VRB-101	Baseline up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20)
Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (AUCinf) for VRB-103 and VRB-101	Arm 1: From Baseline up to Day 29
Half-life (t1/2) for VRB-103 and VRB-101	Baseline up to End of Study (Arm 1: Day 29, Arm 2: Week 10, and Arm 3: Week 20)
Trough Concentration (Ctrough) of VRB-103 and VRB-101	Baseline up to End of Study (Arm 2: Week 10 and Arm 3: Week 20)
AUC Over the Dosing Interval (AUCtau) of VRB-103 and VRB-101	Baseline up to End of Study (Arm 2: Week 10 and Arm 3: Week 20)

Collaborators and Investigators

• Sponsor: Verdiva Bio Dev Limited

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: May 29, 2026
• First Submitted That Met QC Criteria: May 29, 2026
• First Posted (Actual): June 4, 2026

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Glucagon-like peptide-1 (GLP-1); Recombinant human amylin analog
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity
• Other Study ID Numbers: VRB-103-101

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: No
• Studies a U.S. FDA-regulated device product: No