Phase 1 Study to Evaluate the Safety and Tolerability of VK2735

Study Overview
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Brief Summary
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This is a Phase 1, randomized, double-blind, placebo-controlled single and multiple ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of VK2735 in healthy adults and otherwise healthy adults who have an increased body mass index (BMI).

Detailed Description
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This study comprises 3 parts: Part A (Single Ascending Dose [SAD]) will be conducted to assess the safety, tolerability, and PK profile in healthy participants following 1 single SC injection of VK2735 or VK2735 matching placebo (SAD Cohort 1 through SAD Cohort 6). Part B (Multiple Ascending Dose [MAD]) will be conducted to assess the safety, tolerability, PK and PD profile in otherwise healthy participants who have an increased BMI following single SC injections of VK2735 or matched placebo administered once weekly for 4 consecutive weeks (MAD Cohort 1 through MAD Cohort 5). Part C (Multiple Ascending Dose [MAD], PO) will be conducted to assess the safety, tolerability, PK and PD profiles in otherwise healthy, but obese, participants who have a BMI ≥30 kg/m2 following daily oral administration of VK2735 or matched placebo administered for 28 consecutive days (MAD-PO Cohort 1 through MAD-PO Cohort 4, with optional additional cohorts) Safety Review Committee (SRC) meetings will be held prior to dose escalation for Part A (SAD), Part B (MAD), and Part C (MAD-PO) cohorts in the study. The decisions on dose escalation will be based on safety and laboratory data from each cohort.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VK2735, a Dual Glucagon-like Peptide-1 and Gastric Inhibitory Polypeptide Receptor Agonist, in Healthy Adults and Otherwise Healthy Adults Who Have an Increased Body Mass Index

Conditions
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Weight Loss, NASH

Intervention / Treatment
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* Biological: VK2735
* Biological: Placebo
* Drug: VK2735 Placebo
* Drug: VK2735 Drug


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be capable of giving signed informed consent Participants must be medically healthy, with no significant medical history, have no clinically significant abnormalities on physical examination at Screening and/or before administration of the initial dose of IP in the opinion of the Investigator Participant body weight must have been stable (no change greater than 5%) for a minimum 8 weeks prior to Screening Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other clinical study procedures Willing to comply with contraception requirements Exclusion Criteria: Participants with any level of disease or organ system dysfunction as identified during physical examination, medical history or laboratory testing, as assessed by the PI Any surgical or medical condition (active or chronic) that may interfere with IP distribution, metabolism, excretion, or drug absorption Participants may be excluded from the study if they have conditions that might compromise safety or other endpoints in the study as judged by the Sponsor (or designee) or Investigator History or presence of clinically significant acute or unstable cerebrovascular (stroke), hepatic, renal, gastrointestinal, pulmonary, immunological, endocrine, diabetes, hematological, oncological, or central nervous disorder that in the opinion of the Investigator would pose a significant risk for the participant Use of any investigational drug or product, or participation in an investigational drug study within 30 days prior to dosing or 5 half-lives of the drug (whichever is longest) Active smoker and/or user of nicotine-containing products unless the participant agrees to discontinue smoking/use of nicotine-containing products from 2 weeks before first IP dose administration through to study completion, including the Follow-up period Have serum triglycerides > 5.65 mmol/L (500 mg/dL) at Screening Positive serology for hepatitis B surface antigen (HBsAg), hepatitis C antibodies, or HIV

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo (Part A)<br>Placebo administered SC once in healthy participants | Biological: Placebo<br>* Administered SC<br>|
| Experimental: VK2735 (Part A)<br>Escalating doses of VK2735 administered subcutaneously (SC) once in healthy participants. | Biological: VK2735<br>* Administered SC<br>|
| Placebo Comparator: Placebo (Part B)<br>Placebo administered SC once weekly for four weeks in healthy participants | Biological: Placebo<br>* Administered SC<br>|
| Experimental: VK2735 (Part B)<br>Escalating doses of VK2735 administered subcutaneously (SC) once weekly in healthy participants. | Biological: VK2735<br>* Administered SC<br>|
| Placebo Comparator: VK2735 (Part C )<br>Placebo administered orally daily for 28 days in healthy participants | Drug: VK2735 Placebo<br>* Administered orally<br>|
| Experimental: VK2735 (Part C)<br>Escalating doses of VK2735 administered daily (PO) in healthy participants. | Drug: VK2735 Drug<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious AEs (TESAEs) | To evaluate the safety and tolerability of single doses of subcutaneous injections of VK2735 in healthy participants | 8 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the Pharmacokinetic profile of VK2735 | Pharmacokinetic profile of VK2735 by measuring peak plasma concentration (Cmax) | 29 days |