A Multi-part Study of ALG-000184 to Evaluate Safety, Tolerability, Pharmacokinetics and Drug-drug Interaction Potential After Single and Multiple Doses in Healthy Volunteers

A Multi-Part Phase 1 Study in Healthy Volunteers to Evaluate the Drug-Drug Interaction Potential of Multiple Doses of ALG-000184.

This Phase 1 study consists of two parts, all conducted in healthy volunteers (HVs).

In Part 1, the drug-drug interaction (DDI) potential of ALG-000184 will be explored with Itraconazole; participants will be assigned to receive multiple doses of ALG-000184 and Itraconazole over a two week period.

In Part 2, the drug-drug interaction (DDI) potential of ALG-000184 will be explored with Carbamazepine; participants will be assigned to receive multiple doses of ALG-000184 and ascending doses of Carbamazepine over an 18 day period.

The 2 parts may be conducted in parallel.

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: ALG-000184; Drug: Carbamazepine; Drug: Itraconazole (Sporanox)

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • PPD Austin Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria for All Participants:

1. Male or female between 18 and 55 years of age.
2. BMI 18.0 to 32.0 kg/m^2
3. Female participants must have a negative serum pregnancy test at screening.
4. Subjects must have a 12-lead electrocardiogram (ECG) that meets the protocol criteria.

Exclusion Criteria for All Participants:

1. Participants with any current or previous illness that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject or that could prevent, limit, or confound the protocol specified assessments or study results' interpretation.
2. Participants with a past history of cardiac arrhythmias, risk factors for Torsade de Pointes syndrome (e.g., hypokalemia, family history of long QT Syndrome) or history or clinical evidence at screening of significant or unstable cardiac disease etc.
3. Participants with a history of clinically significant drug allergy.
4. Participants with excessive use of alcohol defined as regular consumption of ≥14 standard drinks/week (US CDC 2022)
5. Participants that are unwilling to abstain from alcohol use for 1 week prior to start of the study through end of study follow up.
6. Participants with positive results for urine drug screen, alcohol or cotinine test at screening and Day -1.
7. Participants with Hepatitis A, B, C, E or HIV-1/HIV-2 infection or acute infections such as SARS- CoV-2 infection.
8. Participants with sensitivity to CYP3A4 or P-gp substrates, inhibitors/inducers.
9. Participants with clinically significant abnormal vital signs or physical examination.
10. Participants with renal dysfunction (e.g., estimated creatinine clearance <90 mL/min/1.73 m^2 at screening, calculated by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALG-000184; Single or multiple doses of ALG-000184, an investigational HBV capsid assembly modulator	Drug: ALG-000184; Study Investigational Product
Experimental: Carbamazepine; Multiple doses of carbamazepine, a strong CYP3A4 inducer, to evaluate potential drug-drug interactions with ALG-000184	Drug: ALG-000184; Study Investigational Product; Drug: Carbamazepine; Commercially available supply.
Experimental: Itraconazole; Multiple doses of itraconazole, a strong CYP3A4 inhibitor, to evaluate potential drug-drug interactions with ALG-000184.	Drug: ALG-000184; Study Investigational Product; Drug: Itraconazole (Sporanox); Commercially available supply.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the concentration time curve [AUC]	Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of itraconazole (Part 1)	Up to 24 days
Area under the concentration time curve [AUC]	Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of Carbamazepine (Part 2)	Up to 29 days.
Time to maximum plasma concentration [Tmax]	Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of Carbamazepine (Part 2)	Up to 29 days
Time to maximum plasma concentration [Tmax]	Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of Itraconazole (Part 1)	Up to 24 days
Maximum plasma concentration [Cmax]	Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of Carbamazepine (Part 2)	Up to 29 days
Maximum plasma concentration [Cmax]	Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of Itraconazole (Part 1)	Up to 24 days
Minimum plasma concentration [Cmin]	Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of itraconazole (Part 1)	Up to 24 days
Minimum plasma concentration [Cmin]	Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of Carbamazepine (Part 2)	Up to 29 days
C0 [predose]	Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of itraconazole (Part 1)	Up to 24 days
C0 [predose]	Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of Carbamazepine (Part 2)	Up to 29 days
Half-life [t1/2]	Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of itraconazole (Part 1)	Up to 24 days
Half-life [t1/2]	Pharmacokinetic parameters of ALG-001075 and metabolite ALG-000302 after multiple doses of Carbamazepine (Part 2)	Up to 29 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	The number and severity of treatment emergent adverse events in up to n=24 participants as assessed by DAIDS v2.1(July 2017)	Up to 24 days for Part 1
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	The number and severity of treatment emergent adverse events in up to n=24 participants as assessed by DAIDS v2.1(July 2017)	Up to 29 days for Part 2
Mean Change from Baseline QTc at different exposure levels	Evaluate the concentration-QT relationship of ALG-000175 and metabolite ALG-000302 to determine the QTc prolongation potential of ALG-000184.	Up to 24 days for Part 1.
Mean Change from Baseline QTc at different exposure levels	Evaluate the concentration-QT relationship of ALG-000175 and metabolite ALG-000302 to determine the QTc prolongation potential of ALG-000184.	Up to 29 days for Part 2.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cholesterol	Intends to monitor plasma samples from baseline to measure 4-β-hydroxycholesterol, an induction marker of CYP450.	Up to 24 days in Part 1
Cholesterol	Intends to monitor plasma samples from baseline to measure 4-β-hydroxycholesterol, an induction marker of CYP450.	Up to 29 days in Part 2
Area under the concentration time curve [AUC]	Pharmacokinetic parameters of Carbamazepine and applicable metabolite	29 days
Area under the concentration time curve [AUC]	Pharmacokinetic parameters of itraconazole and applicable metabolite	24 days
Maximum plasma concentration [Cmax]	Pharmacokinetic parameters of Itraconazole and applicable metabolite	24 days
Maximum plasma concentration [Cmax]	Pharmacokinetic parameters of Carbamazepine and applicable metabolite	29 days
Minimum plasma concentration [Cmin]	Pharmacokinetic parameters of Itraconazole and applicable metabolite	24 days
Minimum plasma concentration [Cmin]	Pharmacokinetic parameters of Carbamazepine and applicable metabolite	29 days
C0 [predose]	Pharmacokinetic parameters of Itraconazole and applicable metabolite	24 days
C0 [predose]	Pharmacokinetic parameters of Carbamazepine and applicable metabolite	29 days
Half-life [t1/2]	Pharmacokinetic parameters of Itraconazole and applicable metabolite	24 days
Half-life [t1/2]	Pharmacokinetic parameters of Carbamazepine and applicable metabolite	29 days
Time to maximum plasma concentration [Tmax]	Pharmacokinetic parameters of Itraconazole and applicable metabolite	24 Days
Time to maximum plasma concentration [Tmax]	Pharmacokinetic parameters of carbamazepine and applicable metabolite	29 days

Collaborators and Investigators

• Sponsor: Aligos Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2025
• Primary Completion (Estimated): July 7, 2025
• Study Completion (Estimated): July 7, 2025

Study Registration Dates

• First Submitted: September 25, 2024
• First Submitted That Met QC Criteria: November 1, 2024
• First Posted (Actual): November 4, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 30, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Healthy Volunteer; ALG-000184
• Additional Relevant MeSH Terms: Anti-Infective Agents; Antifungal Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Central Nervous System Depressants; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Sodium Channel Blockers; Membrane Transport Modulators; Tranquilizing Agents; Psychotropic Drugs; Steroid Synthesis Inhibitors; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Anticonvulsants; Antimanic Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; 14-alpha Demethylase Inhibitors; Itraconazole; Carbamazepine
• Other Study ID Numbers: ALG-000184-204

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No