A Study in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics, and Drug-Drug Interaction Potential of Single and Multiple Doses of ALG-097558

A First-in-Human Multi-Part Phase 1 Study in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics, and Drug-Drug Interaction Potential of Single and Multiple Doses of ALG-097558

A multi-part study of ALG-097558 to evaluate safety, tolerability, pharmacokinetics and drug-drug interaction potential after single and multiple doses in healthy volunteers

Study Overview

• Status: Recruiting
• Conditions: COVID-19
• Intervention / Treatment: Drug: Itraconazole; Drug: Placebo; Drug: ALG-097558; Drug: Midazolam; Drug: Carbamazepine; Drug: ALG-097558 in solution formulation; Drug: ALG-097558 in tablet formulation

• Study Type: Interventional
• Enrollment (Estimated): 144
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Stanley Wang; Phone Number: +1 650 222 7159; Email: swang@aligos.com

Study Locations

• United Kingdom
  • London, United Kingdom
    • Recruiting
    • Hammersmith Medicines Research
    • Contact: Karen Dhillon; Phone Number: 020 8961 4130; Email: rec@hmrlondon.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria for All Subjects:

1. Male and Female between 18 and 55 years old
2. BMI 18.0 to 32.0 kg/m^2
3. Female subjects 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 Subjects:

1. Subjects 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. Subjects 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. Subjects with a history of clinically significant drug allergy
4. Excessive use of alcohol defined as regular consumption of ≥14 units/week
5. Unwilling to abstain from alcohol use for 1 week prior to start of the study through end of study follow up
6. Subjects with Hepatitis A, B, C, E or HIV-1/HIV-2 infection or acute infections such as SARS- CoV-2 infection
7. Subjects 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: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALG-097558; Oral doses of ALG-097558 in Healthy Volunteers, up to 20 doses over 10 days	Drug: ALG-097558; single or multiple doses of ALG-097558
Placebo Comparator: Placebo; Oral doses of placebo in Healthy Volunteers, up to 20 doses over 10 days	Drug: Placebo; single or multiple doses of placebo
Experimental: ALG-097558 and Midazolam; Oral doses of ALG-097558, up to 14 doses over 7 days and oral dose of Midazolam, up to 2 doses, over 2 days, in Healthy Volunteers	Drug: ALG-097558; single or multiple doses of ALG-097558; Drug: Midazolam; Multiple doses of Midazolam
Experimental: ALG-097558, Placebo, and, Itraconazole; Oral doses of placebo, up to 2 doses over 2 days, followed by ALG-097558, up to 2 doses over 2 days, and itraconazole up to 10 doses over 10 days, in Healthy Volunteers.	Drug: Itraconazole; Multiple doses of Itraconazole; Drug: Placebo; single or multiple doses of placebo; Drug: ALG-097558; single or multiple doses of ALG-097558
Experimental: ALG-097558 and Carbamazepine; Oral doses of ALG-097558, up to 2 doses over 2 days and oral doses of Carbamazepine, up to 30 doses, over 15 days, in Healthy Volunteers	Drug: ALG-097558; single or multiple doses of ALG-097558; Drug: Carbamazepine; Multiple doses of Carbamazepine
Experimental: ALG-097558 Bioavailability; Oral doses of ALG-097558, up to 3 doses over 3 days, both solution and tablet formulations dosed in fasted state, and tablet formulation dosed in fed state, in Healthy Volunteers	Drug: ALG-097558 in solution formulation; ALG-097558 in solution administered in fasted state; Drug: ALG-097558 in tablet formulation; ALG-097558 in tablet administered in fasted and fed state

What is the study measuring?

Primary 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 as assessed by DAIDS v2.1	Up to 11 days for Part 1
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1	Up to 20 days for Part 2
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1	Up to 20 days for Part 3
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1	Up to 23 days for Part 4
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1	Up to 28 days for Part 5
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1	Up to 17 days for Part 6
Area under the concentration time curve [AUC]	Pharmacokinetic parameters of Midazolam and applicable metabolites	Predose (-2 hours) up to 11 days
Time to maximum plasma concentration [Tmax]	Pharmacokinetic parameters of Midazolam and applicable metabolites	Predose (-2 hours) up to 11 days
Maximum plasma concentration [Cmax]	Pharmacokinetic parameters of Midazolam and applicable metabolites	Predose (-2 hours) up to 11 days
Minimum plasma concentration [Cmin]	Pharmacokinetic parameters of Midazolam and applicable metabolites	Predose (-2 hours) up to 11 days
C0 [predose]	Pharmacokinetic parameters of Midazolam and applicable metabolites	Predose (-2 hours) up to 11 days
Half-life [t1/2]	Pharmacokinetic parameters of Midazolam and applicable metabolites	Predose (-2 hours) up to 11 days
Area under the concentration time curve [AUC]	Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of itraconazole or carbamazepine	Predose (-0.75 hours) up to 19 days
Time to maximum plasma concentration [Tmax]	Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of itraconazole or carbamazepine	Predose (-0.75 hours) up to 19 days
Maximum plasma concentration [Cmax]	Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of itraconazole or carbamazepine	Predose (-0.75 hours) up to 19 days
Minimum plasma concentration [Cmin]	Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of itraconazole or carbamazepine	Predose (-0.75 hours) up to 19 days
C0 [predose]	Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of itraconazole or carbamazepine	Predose (-0.75 hours) up to 19 days
Half-life [t1/2]	Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of itraconazole or carbamazepine	Predose (-0.75 hours) up to 19 days
Area under the concentration time curve [AUC]	Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of ALG-097558 in either solution or tablet formulations and following a high fat diet	Predose (-0.75 hours) up to 9 days
Time to maximum plasma concentration [Tmax]	Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of ALG-097558 in either solution or tablet formulations and following a high fat diet	Predose (-0.75 hours) up to 9 days
Maximum plasma concentration [Cmax]	Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of ALG-097558 in either solution or tablet formulations and following a high fat diet	Predose (-0.75 hours) up to 9 days
Minimum plasma concentration [Cmin]	Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of ALG-097558 in either solution or tablet formulations and following a high fat diet	Predose (-0.75 hours) up to 9 days
C0 [predose]	Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of ALG-097558 in either solution or tablet formulations and following a high fat diet	Predose (-0.75 hours) up to 9 days
Half-life [t1/2]	Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of ALG-097558 in either solution or tablet formulations and following a high fat diet	Predose (-0.75 hours) up to 9 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration [Cmax]	Pharmacokinetic parameters of ALG-097558 in plasma	Predose (-0.75 hours) up to 19 days
Area under the concentration time curve [AUC]	Pharmacokinetic parameters of ALG-097558 in plasma	Predose (-0.75 hours) up to 19 days
Time to maximum plasma concentration [Tmax]	Pharmacokinetic parameters of ALG-097558 in plasma	Predose (-0.75 hours) up to 19 days
Minimum plasma concentration [Cmin]	Pharmacokinetic parameters of ALG-097558 in plasma	Predose (-0.75 hours) up to 19 days
Half-life [t1/2]	Pharmacokinetic parameters of ALG-097558 in plasma	Predose (-0.75 hours) up to 19 days
C0 [predose]	Pharmacokinetic parameters of ALG-097558 in plasma	Predose (-0.75 hours) up to 19 days
Dose Proportionality	Pharmacokinetic parameters of ALG-097558 in plasma	Predose (-0.75 hours) up to 19 days

Collaborators and Investigators

• Sponsor: Aligos Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2023
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): July 30, 2024

Study Registration Dates

• First Submitted: April 10, 2023
• First Submitted That Met QC Criteria: April 21, 2023
• First Posted (Actual): May 3, 2023

Study Record Updates

• Last Update Posted (Estimated): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Healthy Volunteer
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Hormones, Hormone Substitutes, and Hormone Antagonists; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Anticonvulsants; Sodium Channel Blockers; Antimanic Agents; Hormone Antagonists; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; Cytochrome P-450 CYP3A Inducers; 14-alpha Demethylase Inhibitors; Midazolam; Itraconazole; Carbamazepine
• Other Study ID Numbers: ALG-097558-701

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No