First-in-Human Study of VNT-101: Safety, Tolerability, and Pharmacokinetics

NCT07169318 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 23-002475N93022D00015
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

A randomized, double-blind, placebo-controlled Phase 1 study conducted at a single center with approximately 78 healthy adults aged 18-59 years. Part 1 Single Ascending Dose (SAD) will enroll 48 participants into six cohorts (S1-S6) to receive single oral doses of VNT-101 (100-1500 mg) or placebo under fasting or fed (S5 only) conditions. Part 2 Multiple Ascending Dose (MAD) will enroll 30 participants into three cohorts (M1-M3) to receive multiple oral doses of VNT-101 (250-750 mg BID Days 1-5, QD Day 6) or placebo under fasting conditions. Dose escalation in both parts will proceed after Protocol Safety Review Team (PSRT) review. The primary objective for Part 1 is to evaluate the safety and tolerability of single ascending oral (SAD) doses of VNT-101 in healthy adult participants under either fasting or fed conditions. The primary objective for part 2 is to evaluate the safety and tolerability of multiple ascending oral (MAD) doses of VNT-101 in healthy adult participants.

Conditions

Influenza

Keywords

Double-Blind; First-in-Human; Food-Effect Study; Influenza; Multiple Ascending Dose; Nucleoprotein; Placebo-Controlled; Randomized; Safety; Single Ascending Dose; vnt-101

Outcome Measures

Primary Outcomes (41)

• Change from baseline blood pressure (BP)

  Day 1 through Day 13

• Change from baseline heart rate (HR)

  Day 1 through Day 13

• Change from baseline heart rhythm, measured by a 12-lead safety Electrocardiogram (ECG)

  12-lead ECG will be measured in triplicate

  Day 1 through Day 13

• Change from baseline Hemoglobin

  Day 1 through Day 8

• Change from baseline in Absolute neutrophil count

  Day 1 through Day 13

• Change from baseline in active partial thromboplastin time

  Day 1 through Day 13

• Change from baseline in blood in urine

  Day 1 through Day 13

• Change from baseline in direct serum Bilirubin

  Day 1 through Day 13

• Change from baseline in Hematocrit

  Day 1 through Day 13

• Change from baseline in international normalized ratio

  Day 1 through Day 13

• Change from baseline in lipase in Single Ascending Dose (SAD)

  Day 1 through Day 13

• Change from baseline in prothrombin time

  Day 1 through Day 13

• Change from baseline in red blood cell count

  Day 1 through Day 13

• Change from baseline in serum Alanine aminotransferase

  Day 1 through Day 13

• Change from baseline in serum Albumin

  Day 1 through Day 13

• Change from baseline in serum Alkaline phosphatase

  Day 1 through Day 13

• Change from baseline in serum Aspartate Aminotransferase

  Day 1 through Day 13

• Change from baseline in serum Bicarbonate

  Day 1 through Day 13

• Change from baseline in serum Blood Urea Nitrogen

  Day 1 through Day 13

• Change from baseline in serum Chloride

  Day 1 through Day 13

• Change from baseline in serum Creatinine

  Day 1 through Day 13

• Change from baseline in serum Glucose

  Day 1 through Day 13

• Change from baseline in serum Potassium

  Day 1 through Day 13

• Change from baseline in serum Sodium

  Day 1 through Day 13

• Change from baseline in total serum Bilirubin

  Day 1 through Day 13

• Change from baseline in urine leukocyte esterase

  Day 1 through Day 13

• Change from baseline in urine nitrate level

  Day 1 through Day 13

• Change from baseline in urine protein

  Day 1 through Day 13

• Change from baseline in White blood cell count with differential

  Day 1 through Day 13

• Change from baseline oral temperature

  Day 1 through Day 13

• Change from baseline Platelet count

  Day 1 through Day 13

• Change from baseline PR interval, measured by a 12-lead safety Electrocardiogram (ECG)

  12-lead ECG will be measured in triplicate

  Day 1 through Day 13

• Change from baseline QRS duration, measured by a 12-lead safety Electrocardiogram (ECG)

  12-lead ECG will be measured in triplicate

  Day 1 through Day 13

• Change from baseline QT interval, measured by a 12-lead safety Electrocardiogram (ECG)

  12-lead ECG will be measured in triplicate

  Day 1 through Day 13

• Change from baseline QTcF interval, measured by a 12-lead safety Electrocardiogram (ECG)

  12-lead ECG will be measured in triplicate

  Day 1 through Day 13

• Change from baseline respiratory rate (RR)

  Day 1 through Day 13

• Change from baseline RR interval, measured by a 12-lead safety Electrocardiogram (ECG)

  12-lead ECG will be measured in triplicate

  Day 1 through Day 13

• Incidence of Treatment Emergent Adverse Events (TEAEs)

  Day 1 through Day 13

• Proportion of participants with findings from cardiac telemetry

  Cardiac telemetry will monitor heart rate and rhythm

  Day 1 through Day 13

• Proportion of participants with findings from physical examination.

  Day 1 through Day 8

• Proportion of participants with findings from visual exam of clean-catch urine sample

  Day 1 through Day 13

Secondary Outcomes (23)

• Accumulation ratio based on area under the concentration curve (RA_AUC) in plasma

  Through Day 9

• Accumulation ratio based on Cmax (RA_Cmax) in plasma

  Through Day 9

• Amount of drug excreted unchanged between t1 and t2 (Aet1-t2,ss) in urine

  Through Day 9

• Apparent volume of distribution at terminal phase (VZ/F) in plasma

  Day 1 through Day 4

• Apparent volume of distribution at terminal phase at a steady state (Vz,ss/F) in plasma

  Through Day 9

Study Arms (18)

Part 1 (SAD) Cohort S1 Arm 1

EXPERIMENTAL

Healthy adult participants \>/= 18 to 59 years will receive a Single Ascending Dose (SAD) of VNT-101 at 100 mg administered orally with approximately 240ml of water under fasting conditions. N=6

Drug: VNT-101

Part 1 (SAD) Cohort S1 Arm 2

PLACEBO COMPARATOR

Healthy adult participants \>/= 18 to 59 years will receive a Single Ascending Dose (SAD) of Placebo for VNT-101 at 100mg administered orally with approximately 240ml of water under fasting conditions. N=2

Other: Placebo for VNT-101

Part 1 (SAD) Cohort S2 Arm 1

EXPERIMENTAL

Healthy adult participants \>/= 18 to 59 years will receive Single Ascending Dose (SAD) of VNT-101 at 250 mg administered orally with approximately 240ml of water under fasting conditions. N=6

Drug: VNT-101

Part 1 (SAD) Cohort S2 Arm 2

PLACEBO COMPARATOR

Healthy adult participants \>/= 18 to 59 years will receive a Single Ascending Dose (SAD) of Placebo for VNT-101 at 250mg administered orally with approximately 240ml of water under fasting conditions. N=2

Other: Placebo for VNT-101

Part 1 (SAD) Cohort S3 Arm 1

EXPERIMENTAL

Healthy adult participants \>/= 18 to 59 years will receive a Single Ascending Dose (SAD) of VNT-101 at 500 mg administered orally with approximately 240ml of water under fasting conditions. N=6

Drug: VNT-101

Part 1 (SAD) Cohort S3 Arm 2

PLACEBO COMPARATOR

Healthy adult participants \>/= 18 to 59 years will receive a Single Ascending Dose (SAD) of Placebo for VNT-101 at 500mg administered orally with approximately 240ml of water under fasting conditions. N=2

Other: Placebo for VNT-101

Part 1 (SAD) Cohort S4 Arm 1

EXPERIMENTAL

Healthy adult participants \>/= 18 to 59 years will receive a Single Ascending Dose (SAD) of VNT-101 at 1000 mg administered orally with approximately 240ml of water under fasting conditions. N=6

Drug: VNT-101

Part 1 (SAD) Cohort S4 Arm 2

PLACEBO COMPARATOR

Healthy adult participants \>/= 18 to 59 years will receive Single Ascending Dose (SAD) of Placebo for VNT-101 at 1000mg administered orally with approximately 240ml of water under fasting conditions. N=2

Other: Placebo for VNT-101

Part 1 (SAD) Cohort S5 Arm 1

EXPERIMENTAL

Healthy adult participants \>/= 18 to 59 years from Cohort S3 will receive a Single Ascending Dose (SAD) of VNT-101 at 500 mg administered orally with approximately 240ml of water under fed (high-fat meal) conditions. N=6

Drug: VNT-101

Part 1 (SAD) Cohort S5 Arm 2

PLACEBO COMPARATOR

Healthy adult participants \>/= 18 to 59 years from Cohort 3 will receive a Single Ascending Dose (SAD) of Placebo for VNT-101 at 500mg administered orally with approximately 240ml of water under fed (high-fat meal) conditions. N=2

Other: Placebo for VNT-101

Part 1 (SAD) Cohort S6 Arm 1

EXPERIMENTAL

Healthy adult participants \>/= 18 to 59 years will receive a Single Ascending Dose (SAD) of VNT-101 at 1500 mg administered orally with approximately 240ml of water under fasting conditions. N=6

Drug: VNT-101

Part 1 (SAD) Cohort S6 Arm 2

PLACEBO COMPARATOR

Healthy adult participants \>/= 18 to 59 years will receive a Single Ascending Dose (SAD) of Placebo for VNT-101 at 1500mg administered orally with approximately 240ml of water under fasting conditions. N=2

Other: Placebo for VNT-101

Part 2 (MAD) Cohort M1 Arm 1

EXPERIMENTAL

Following Single Ascending Dose (SAD) safety and Pharmacokinetics (PK) data review by the Safety Monitoring Committee (SMC), healthy adult participants \>/= 18 to 59 years will receive Multiple Ascending Dose (MAD) of 250 mg of VNT-101 twice daily (BID) on Days 1 through 5 and 500mg of VNT-101 once daily (QD) on Day 6 administered orally with approximately 240ml of water under fasting conditions. N=8

Drug: VNT-101

Part 2 (MAD) Cohort M1 Arm 2

PLACEBO COMPARATOR

Following Single Ascending Dose (SAD) safety and Pharmacokinetics (PK) data review by the Safety Monitoring Committee (SMC), healthy adult participants \>/= 18 to 59 years will receive Multiple Ascending Dose (MAD) of 250 mg of Placebo for VNT-101 twice daily (BID) on Days 1 through 5 and 500mg of Placebo for VNT-101 once daily (QD) on Day 6 administered orally with approximately 240ml of water under fasting conditions. N=2

Other: Placebo for VNT-101

Part 2 (MAD) Cohort M2 Arm 1

EXPERIMENTAL

Following Single Ascending Dose (SAD) safety and PK data review by the Safety Monitoring Committee (SMC), healthy adult participants \>/= 18 to 59 years will receive Multiple Ascending Dose (MAD) of 500 mg of VNT-101 twice daily (BID) on Days 1 through 5 and 1000mg of VNT-101 once daily (QD) on Day 6 administered orally with approximately 240ml of water under fasting conditions. N=8

Drug: VNT-101

Part 2 (MAD) Cohort M2 Arm 2

PLACEBO COMPARATOR

Following Single Ascending Dose (SAD) safety and Pharmacokinetics (PK) data review by the Safety Monitoring Committee (SMC), healthy adult participants \>/= 18 to 59 years will receive Multiple Ascending Dose (MAD) of 500 mg of Placebo for VNT-101 twice daily (BID) on Days 1 through 5 and 1000mg of Placebo for VNT-101 once daily (QD) on Day 6 administered orally with approximately 240ml of water under fasting conditions. N=2

Other: Placebo for VNT-101

Part 2 (MAD) Cohort M3 Arm 1

EXPERIMENTAL

Following Single Ascending Dose (SAD) safety and PK data review by the Safety Monitoring Committee (SMC), healthy adult participants \>/= 18 to 59 years will receive Multiple Ascending Dose (MAD) of 750 mg of VNT-101 twice daily (BID) on Days 1 through 5 and 1500mg of VNT-101 once daily (QD) on Day 6 administered orally with approximately 240ml of water under fasting conditions. N=8

Drug: VNT-101

Part 2 (MAD) Cohort M3 Arm 2

PLACEBO COMPARATOR

Following Single Ascending Dose (SAD) safety and Pharmacokinetics (PK) data review by the Safety Monitoring Committee (SMC), healthy adult participants \>/= 18 to 59 years will receive Multiple Ascending Dose (MAD) of 750 mg of Placebo for VNT-101 twice daily (BID) on Days 1 through 5 and 1500mg of Placebo for VNT-101 once daily (QD) on Day 6 administered orally with approximately 240ml of water under fasting conditions. N=2

Other: Placebo for VNT-101

Interventions

Placebo for VNT-101 OTHER

Capsules will be size 00 and filled with microcrystalline cellulose

Part 1 (SAD) Cohort S1 Arm 2; Part 1 (SAD) Cohort S2 Arm 2; Part 1 (SAD) Cohort S3 Arm 2; Part 1 (SAD) Cohort S4 Arm 2; Part 1 (SAD) Cohort S5 Arm 2; Part 1 (SAD) Cohort S6 Arm 2; Part 2 (MAD) Cohort M1 Arm 2; Part 2 (MAD) Cohort M2 Arm 2; Part 2 (MAD) Cohort M3 Arm 2

VNT-101 DRUG

VNT-101 is an orally bioavailable, direct-acting antiviral with a novel mechanism of action - inhibiting oligomerization of the influenza nucleoprotein (NP) and thereby inhibiting viral ribonucleic acid (RNA) synthesis.

Part 1 (SAD) Cohort S1 Arm 1; Part 1 (SAD) Cohort S2 Arm 1; Part 1 (SAD) Cohort S3 Arm 1; Part 1 (SAD) Cohort S4 Arm 1; Part 1 (SAD) Cohort S5 Arm 1; Part 1 (SAD) Cohort S6 Arm 1; Part 2 (MAD) Cohort M1 Arm 1; Part 2 (MAD) Cohort M2 Arm 1; Part 2 (MAD) Cohort M3 Arm 1

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provides written informed consent prior to the initiation of any trial procedures.
• Able to understand and agrees to comply with all planned trial procedures and be available for all study visits.
• Healthy, adult, male or female (of non-childbearing potential only\*), 18-59 years of age, inclusive, at the screening visit.
• \* Female participants of non-childbearing potential must be either surgically sterile (i.e., hysterectomy, bilateral tubal ligation, bilateral tubal occlusion \[hysteroscopic sterilization\], salpingectomy, and/or bilateral oophorectomy at least 26 weeks before Screening) or post-menopausal, defined as spontaneous amenorrhea for at least a year, with follicle-stimulating hormone (FSH) in the post-menopausal range at Screening, based on the central laboratory ranges.
• Continuous non-smoker who has not used nicotine-, tobacco-, cannabis-, or cannabidiol-containing products\*\* prior to the first dosing based on participant self-reporting.
• \*\*The period before first dose is at least 3 months for tobacco and associated products and at least 60 days for cannabis and associated products.
• Body mass index (BMI)\>/=18.0 and \</= 30.0 kg/m\^2 at the screening visit.
• Medically healthy\*\*\* with no clinically significant medical history, physical examination, laboratory profiles, vital signs, and ECGs, as deemed by the Principal Investigator (PI) or designee,
• \*\*\*Including the following:
• Supine diastolic blood pressure is \>/= 40 mmHg and \</= 90 mmHg at the screening visit.
• Supine systolic blood pressure is \>/= 90 mmHg and \</= 140 mmHg at the screening visit.
• Supine heart rate is \>/= 60 bpm and\</= 100 bpm at the screening visit.
• QTcF interval is \</= 460 msec (males) and \</=470 msec (females) and has ECG findings considered normal or not clinically significant by the PI or designee at the screening visit.
• Estimated creatinine clearance \>/= 80 mL/min based on the Cockroft-Gault equation and creatinine \<1.50 mg/dL at the screening visit.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) is not greater than 1.1 times the upper limit of normal (ULN), as specified by the testing laboratory.

You may not qualify if:

• History or presence of clinically significant medical or psychiatric condition or disease, making the participant unsuitable for enrollment in the opinion of the PI or designee.
• History of severe allergic or anaphylactic reactions to any prescription or non-prescription drug or vaccine.
• Participants who took any prescription medications within 14 days of first dosing or within 5 half-lives of the drug, whichever is longer.
• Participants who took any over the counter (OTC) medication/vitamins/herbal supplements\* in the last 7 days prior to first dosing.
• \*Exception for occasional use of OTC acetaminophen (paracetamol) 325 to 500 mg every 4 hours not to exceed 3000 mg/day.
• History or diagnosis of a cardiovascular disease condition, including myocardial infarction, angina, congenital heart disease, cardiomyopathy, hypertension, or hypercholesteremia\*\*.
• \*\*Defined as: clinically significant hypercholesteremia with high low-density lipoprotein (LDL) cholesterol (\>/= 160 mg/dL)
• Increased risk for peptic ulcer\*\*\*
• \*\*\*Defined as: participants with a history of gastric or duodenal ulcer, chronic non-steroidal anti-inflammatory drug use in the past 3 months, current smokers, alcohol consumption of \> 21 alcoholic units per week (where 1 unit = 284 mL of beer, 25 mL of 40% spirit or a 125 mL of wine) or chronic atrophic gastritis,
• Female participant with a positive pregnancy test at the screening visit or at baseline or who is lactating.
• Positive urine drug toxicology test (or cotinine or alcohol results) at the screening visit or check-in.
• Has been on a diet incompatible with the on-study diet\*\*\*\*, in the opinion of the PI or designee, within the 30 days prior to the first dosing,
• \*\*\*\*including consumption of grapefruit/Seville orange within 14 days prior to first dosing,
• For Cohorts S2, S3, and S5 only, is known to be intolerant of a high fat/high calorie diet.
• Participants who are unlikely to comply with the study protocol OR those who would not be suitable candidates for participation in the opinion of the investigator.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Altasciences Inc - Kansas City

Overland Park, Kansas, 66212, United States

RECRUITING

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Central Study Contacts

Nadine Mokhallati

CONTACT

19136961601; NMokhallati@altasciences.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: For both parts of the study, participants and the clinical personnel involved in the collection, monitoring, revision, or evaluation of AEs, or personnel who could have an impact on the outcome of the study will be blinded with respect to the participant's treatment assignment (VNT-101 or placebo)
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2025
• First Posted: September 11, 2025
• Study Start: September 16, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: April 17, 2026

Record last verified: 2025-09-05

Locations

US (1)