NCT06847698

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

Phase 1, Double-Blinded, Placebo-Controlled, Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) Safety and Pharmacokinetics Trial of AVR-48

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 48 (estimated)
• Sponsor: AyuVis Research, Inc. · Industry
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

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.

Detailed description

This is a Phase 1, 2-part, double-blinded, placebo-controlled, randomized SAD/MAD study. The study will include 2 parts: * Part A: SAD phase * Part B: MAD phase Part A - SAD phase Healthy adult subjects will be randomized to receive a single IV dose of either AVR-48 or placebo in each of 3 planned SAD cohorts. Each cohort will consist of 8 subjects in a 3:1 (active:placebo) ratio to have a total of 6 subjects receiving AVR-48 and 2 subjects receiving placebo. Each cohort will be comprised of 50% male and 50% female subjects. All SAD cohorts will be dosed according to a sentinel dosing design to ensure safety. Initially, 2 subjects will be dosed; 1 subject will be dosed with AVR-48 and 1 subject with placebo. Blood samples for PK and safety clinical laboratory tests will be collected over the following 24 hours. If the site Principal Investigator (PI), in conjunction with the AyuVis sponsored Independent Medical Monitor, determines that acceptable safety is observed in the sentinel administration, the remaining subjects in the cohort will be dosed and identical safety and PK procedures will be performed; 5 subjects will be dosed with AVR-48 and 1 subject with placebo. Sentinel subjects will be dosed at least 48 hours prior to enrolling the remaining subjects of the cohort. All subjects will be followed for 48 hours post-dose. Blood samples will be collected periodically for PK, cytokine panels, metabolite assessment, and safety labs; urine samples will be collected periodically for metabolite assessment, and routine safety assessments will be completed daily. Escalation to the next higher dose will only proceed if none of the stopping criteria have been reached and when the safety and tolerability and available plasma PK analysis of the previous dose are acceptable to the site PI, Sponsor, and Safety Monitoring Committee (SMC). A minimum of 3 days will separate each dose escalation. Part B - MAD phase Healthy adult subjects will be randomized to receive multiple IV doses of either AVR-48 or placebo in each of 3 planned MAD cohorts. Each cohort will consist of 8 subjects in a 3:1 (active: placebo) ratio to have a total of 6 subjects receiving AVR-48 and 2 subjects receiving placebo. A balance of male and female subjects in each cohort will be attempted, but the final ratio of subject sex will be determined by the available subjects who pass screening at the time of enrollment. For Cohort 1 and Cohort 2, AVR-48 or matching placebo will be administered twice daily, every 12 hours, for a total of 13 doses over 7 days. For Cohort 3, AVR-48 will be administered once daily, for a total of 7 doses over 7 days. Subjects will be monitored for 48 hours after the last dose and will attend a follow-up visit 7 days after dosing completes. Blood samples will be collected periodically for PK, cytokine panels, metabolite assessment, and safety labs; urine samples will be collected periodically for metabolite assessment, and routine safety assessments will be completed daily.

Conditions

• Safety Issues
• Tolerability
• Pharmacokinetics
• Pharmacodynamics

Interventions

Type	Name	Description
DRUG	AVR-48	Investigational drug reconstituted in normal saline will be administered via IV
DRUG	Placebo	Normal saline will be administered via IV

Timeline

• Start date: 2025-06-01
• Primary completion: 2025-10-01
• Completion: 2025-11-01
• First posted: 2025-02-26
• Last updated: 2025-04-06

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study