First-in-Human Single and Multiple Dose of HL-400

NCT06997484 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HL-400-101
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind, placebo-controlled, dose-escalation study in healthy subjects to evaluate the safety, tolerability, pharmacokinetics of HL-400 (a NLRP3 inhibitor) following oral single and multiple ascending dose administration.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (9)

• Number and percentage of participants with adverse events (AEs)

  To evaluate the safety and tolerability of HL-400 following oral single and multiple ascending dose administration.

  From the time of taking first dose of study drug to 7 days after the last dose.

• Number and percentage of adverse events (AEs) according to severity

  To evaluate the safety and tolerability of HL-400 following oral single and multiple ascending dose administration.

  From the time of taking first dose of study drug to 7 days after the last dose.

• Change in 12-lead electrocardiogram (ECG) parameters (PR Interval, QRS Complex, QT Interval, QTC Interval) from baseline

  To evaluate the safety and tolerability of HL-400 following oral single and multiple ascending dose administration.

  From baseline to 7 days after the last dose.

• Single Ascending Dose (SAD) Cohorts: Maximum observed plasma concentration (Cmax) of HL-400

  To characterize the PK in the plasma of HL-400 following oral single dose administration.

  From 0.5 hour to 72 hours post-dose.

• Single Ascending Dose (SAD) Cohorts: Time to reach maximum observed plasma concentration (Tmax) of HL-400

  To characterize the PK in the plasma of HL-400 following oral single dose administration.

  From 0.5 hour to 72 hours post-dose.

• Single Ascending Dose (SAD) Cohorts: Plasma decay half-life (t1/2) of HL-400

  To characterize the PK in the plasma of HL-400 following oral single dose administration.

  From 0.5 hour to 72 hours post-dose.

• Single Ascending Dose (SAD) Cohorts: Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUCinf) of HL-400

  To characterize the PK in the plasma of HL-400 following oral single dose administration.

  From 0.5 hour to 72 hours post-dose.

• Multiple Ascending Dose (MAD) Cohorts: Maximum observed plasma concentration (Cmax) of HL-400

  To characterize the PK in the plasma of HL-400 following oral multiple ascending dose administration.

  From Day 1 pre-dose to 72 hours after the last dose.

• Multiple Ascending Dose (MAD) Cohorts: Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUCinf) of HL-400

  To characterize the PK in the plasma of HL-400 following oral multiple ascending dose administration.

  From Day 1 pre-dose to 72 hours after the last dose.

Secondary Outcomes (2)

• 1.The cerebrospinal fluid (CSF) cohort: Maximum observed concentration (Cmax) of HL-400 in the CSF

  From Day 1 pre-dose to 24 hours after the last dose

• The cerebrospinal fluid (CSF) cohort: Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUCinf) of HL-400 in the CSF

  From Day 1 pre-dose to 24 hours after the last dose

Study Arms (2)

HL-400

ACTIVE COMPARATOR

Part 1:Experimental: Single oral dose of HL-400, Single ascending doses, sequential assignment group design; Part 2: Experimental: Multiple oral doses of HL-400, Multiple ascending doses, once a day (QD) for 14 days, sequential assignment group design; Part 3: Experimental: Multiple oral doses of HL-400, QD for 5 days.

Drug: HL-400

Placebo

PLACEBO COMPARATOR

Part 1: Placebo comparator: Single oral dose of placebo, single doses, matching placebo; Part 2: Placebo comparator: Multiple oral doses of placebo, multiple ascending doses, QD for 14 days, matching placebo

Drug: Placebo

Interventions

HL-400 DRUG

Part 1:Experimental: Single oral dose of HL-400, Single ascending doses, sequential assignment group design; Part 2: Experimental: Multiple oral doses of HL-400, Multiple ascending doses, QD for 14 days, sequential assignment group design; Part 3: Experimental: Multiple oral doses of HL-400, QD for 5 days.

HL-400

Placebo DRUG

Part 1: Placebo comparator: Single oral dose of placebo, single doses, matching placebo; Part 2: Placebo comparator: Multiple oral doses of placebo, multiple ascending doses, QD for 14 days, matching placebo.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are capable of giving written informed consent and complying with study procedures, schedule, requirements, and restrictions.
• Are between the ages of 18 and 65 years, inclusive, at screening.
• Female subjects have a negative serum hCG pregnancy test result at screening andDay （-1）, agree to refrain from ova donation for at least 3 months after the last dose, and willingness to comply with protocol-specified contraceptive methods.
• Male subjects with female partners of reproductive potential must agree to practice abstinence or to use a condom (male subject) plus an additional barrier method (female partner) of contraception for the duration of the study and for at least 3 months after last dosing; must also agree to refrain from sperm donation for at least 3 months after the last dose.
• Considered healthy by the Investigator, based on subject's reported medical history, full physical examination, clinical laboratory tests, 12-lead ECG, and vital signs.
• Non-smoker for at least 6 months prior to screening.
• Body mass index (BMI) of 18.0 to 32.0 kg/m2 inclusive, except for MAD Cohort 3 subjects with a BMI of of 32.0 to 42.0 kg/m2 inclusive.

You may not qualify if:

• Clinically significant history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, or drug hypersensitivity as determined by the Investigator.
• Pregnant (as determined by pregnancy test result) or breastfeeding women.
• History of chronic diarrhea, malabsorption, unexplained weight loss, food allergies or intolerance.
• Positive blood screen for human immunodeficiency virus (HIV 1/2), hepatitis B surface antigen (HBsAg), or hepatitis C antibody.
• A positive screen for alcohol or drugs of abuse at screening or Day -1.
• An unwillingness or inability to comply with food and beverage restrictions during study participation.
• Volunteers who have participated in any investigational drug or device study within past 3 months prior to dosing.
• Any condition or finding that in the Investigators opinion would put the subject or study conduct at risk if the subject were to participate in the study.

Sponsors & Collaborators

• Highlightll Pharmaceutical (USA) LLC: lead

Study Sites (1)

Pharmaron CPC, Inc.

Baltimore, Maryland, 21201, United States

RECRUITING

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2025
• First Posted: May 30, 2025
• Study Start: April 25, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): October 27, 2026
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)