Single Ascending Dose and Multiple Ascending Dose Study of AVR-48

NCT06847698 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: AVR-48-01-001
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1 (healthy adult volunteers), 2-part, double-blind, randomized, placebo controlled trial to evaluate the safety and pharmacokinetic (PK) profiles of escalating single doses of AVR-48 versus placebo (SAD) and escalating multiple doses of AVR-48 versus placebo (MAD). SAD will be initiated first and include a sentinel dosing design. MAD will not utilize a sentinel design unless the safety monitoring committee requests the addition of sentinels. The MAD will be initiated once the lowest doses from SAD are deemed safe.

Conditions

Safety Issues; Tolerability; Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (5)

• Number of participants who experience Adverse Events (AEs), Serious Adverse Events

  Number of AEs, SAEs, and discontinuation due to AEs

  Up to 16 days

• Number of participants who experience ECG abnormalities

  Number of participants with potentially clinically significant ECG readings

  Up to 16 days

• Number of participants who experience vital sign abnormalities

  Number of participants with potentially clinically significant vital sign values

  Up to 16 days

• Number of participants who experience laboratory test abnormalities

  Number of participants with potentially clinically significant laboratory test results

  Up to 16 days

• Number of participants who experience physical examination abnormalities

  Number of participants with potentially significant physical examination findings

  Up to 16 days

Secondary Outcomes (13)

• PK of AVR-48 in plasma: Area under the plasma-concentration time curve (AUC)

  Up to 8 days

• Title: PK of AVR-48 in plasma: Area under the concentration time curve, from time 0 to the last observed non-zero concentration (AUC0-tlast)

  Up to 8 days

• PK of AVR-48 in plasma: Maximum observed concentration (Cmax)

  Up to 8 days

• PK of AVR-48 in plasma: Trough or minimum concentration (Ctrough)

  Up to 8 days

• PK of AVR-48 in plasma: Concentration at the end of the dosing interval (Ct)

  Up to 8 days

Study Arms (2)

Drug: AVR-48

EXPERIMENTAL

AVR-48 is a small molecule with TLR4 modulating activity and macrophage modulator

Drug: AVR-48

Drug: Placebo

PLACEBO COMPARATOR

0.9% saline

Drug: Placebo

Interventions

AVR-48 DRUG

Investigational drug reconstituted in normal saline will be administered via IV

Drug: AVR-48

Placebo DRUG

Normal saline will be administered via IV

Drug: Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated informed consent form (ICF).
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Healthy adult male or female, aged 18 to 55, inclusive, at Screening.
• Continuous non smoker who has not used nicotine containing products (including e- vaping) for at least 3 months prior to the first dosing and throughout the study
• Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at screening, and a minimum weight of at least 50.0 kg and a maximum weight of 100.0 kg at screening.
• Medically healthy with no clinically significant abnormalities in medical history, physical and neurologic examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee.
• If female of childbearing potential, must be consistently using an effective method of contraception from screening visit until 30 days after the last drug administration.
• If female and not of childbearing potential, must be either surgically sterile or post menopausal (i.e., more than 1 year since last menstrual period).
• A non-vasectomized, male subject must agree to use an effective method of birth control with female partners of childbearing potential during the study and to refrain from donating sperm for 90 days following dosing.
• No restrictions are required for a vasectomized male subject provided his vasectomy has been performed 4 months or more (and have official documentation) prior to Study Day 1. A subject who has been vasectomized less than 4 months prior to Study Day 1 or does not have official documentation of his vasectomy must follow the same restrictions as a non-vasectomized subject.

You may not qualify if:

• Are mentally or legally incapacitated or have significant emotional problems at the time of the screening visit or expected during the conduct of the study in the opinion of the PI or designee.
• History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.
• History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
• History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing.
• Has had surgery or any medical condition within 6 months prior to first dosing which may affect the distribution, metabolism, or elimination of the study drug, in the opinion of the PI or designee.
• Female subjects with a positive pregnancy test or who are lactating.
• Positive urine drug or alcohol results at screening or first check-in.
• Positive cotinine results at screening.
• Positive result at screening for tuberculosis (i.e., positive result for QuantiFERON TB-Gold).
• Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
• Unable to refrain from or anticipates the use of:
• Any drug, including prescription and non prescription medications, herbal remedies, or vitamin supplements beginning 14 days prior to the first dosing and throughout the study. After first dosing, acetaminophen (up to 2 g per 24 hours) may be administered at the discretion of the PI or designee. Hormone replacement therapy will be allowed.
• Donation or loss of 50 to 499 mL whole blood within 30 days or more than 499 mL whole blood within 56 days prior to the first dosing.
• Plasma donation within 14 days prior to the first dosing.
• Participation in another clinical study within 30 days prior to the first dosing. The 30 day window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of Period 1 of the current study.

Sponsors & Collaborators

• AyuVis Research, Inc.: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

PPD

Austin, Texas, 78744, United States

Location

Study Officials

• Suchismita Acharya, PhD

  AyuVis Research, Inc.

  STUDY DIRECTOR

Central Study Contacts

Study Principal Investigator

CONTACT

877-362-2608; sacharya@ayuvis.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The investigators, study coordinators, study subjects and the Sponsor will be blinded to treatment assignment.
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A: Eight (8) subjects will participate in each of the 3 dose groups. Subjects will be randomized to receive either AVR-48 or placebo by IV (6 active, 2 placebo per group of 8). Part B: Eight (8) subjects will participate in each of the 3 dose groups. Subjects will be randomized to receive either AVR-48 or placebo by IV (6 active, 2 placebo per group of 8).

Study Record Dates

• First Submitted: August 27, 2024
• First Posted: February 26, 2025
• Study Start: June 1, 2025
• Primary Completion: October 1, 2025
• Study Completion: November 1, 2025
• Last Updated: April 6, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)