A Study of ALG-125755 to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics After Single Doses in Healthy Volunteers, and Single and Multiple Doses in CHB Subjects

Sponsor

Aligos Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05561530

Collaborator

(none)

120

Enrollment

Locations

Arms

38.8

Anticipated Duration (Months)

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A randomized study of ALG-125755 to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics after single doses in healthy volunteers, and single and multiple doses in CHB subjects

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis B	Drug: ALG-125755 Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase 1/1b, Double-Blind, Randomized, Placebo-Controlled, First-in-Human Study of Subcutaneously Administered ALG-125755 to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics After Single Ascending Doses in Healthy Volunteers (Part 1) and Subjects With Chronic Hepatitis B (Part 2), and Multiple Doses in Subjects With Chronic Hepatitis B (Part 3)

Actual Study Start Date :

Oct 7, 2022

Anticipated Primary Completion Date :

Jul 1, 2025

Anticipated Study Completion Date :

Dec 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ALG-125755 Subcutaneous injections of ALG-125755 in HV or CHB subjects, up to 6 injections over the course of up to 72 weeks	Drug: ALG-125755 single or multiple doses of ALG-125755
Placebo Comparator: Placebo Subcutaneous injections of placebo in HV or CHB subjects, up to 6 injections over the course of up to 72 weeks	Drug: Placebo single or multiple doses of placebo

Arm

Intervention/Treatment

Experimental: ALG-125755

Subcutaneous injections of ALG-125755 in HV or CHB subjects, up to 6 injections over the course of up to 72 weeks

Drug: ALG-125755

single or multiple doses of ALG-125755

Placebo Comparator: Placebo

Subcutaneous injections of placebo in HV or CHB subjects, up to 6 injections over the course of up to 72 weeks

Drug: Placebo

single or multiple doses of placebo

Outcome Measures

Primary Outcome Measures

Incidence and severity of treatment emergent adverse events as assessed by DAIDS v2.1 of various doses of ALG-125755 in HV subjects and CHB subjects [Up to 32 days for Part 1]
Incidence and severity of treatment emergent adverse events as assessed by DAIDS v2.1 [Up to 52 days for Part 2]
Incidence and severity of treatment emergent adverse events as assessed by DAIDS v2.1 [Up to 616 days for Part 3]

Secondary Outcome Measures

Maximum plasma concentration (Cmax) [Predose (0 hours) up to 616 days]
Pharmacokinetic parameters of ALG-125755 in plasma
Area under the concentration time curve [AUC] [Predose (0 hours) up to 616 days]
Pharmacokinetic parameters of ALG-125755 in plasma
Time to maximum plasma concentration [Tmax] [Predose (0 hours) up to 616 days]
Pharmacokinetic parameters of ALG-125755 in plasma
Antiviral activity of ALG-125755 as measured by quantitative changes in serum [Predose (0 hours) up to 616 days]
Pharmacokinetic parameters of ALG-125755 in plasma
Minimum plasma concentration (Cmin) [Predose (0 hours) up to 616 days]
Pharmacokinetic parameters of ALG-125755 in plasma
Change in HBsAg from baseline through up to 112 days from last dose in multiple dose HBV infected subjects [screening to up to 112 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria for All Subjects:

Female subjects must have a negative serum pregnancy test at screening
Subjects must have a 12-lead electrocardiogram (ECG) that meets the protocol criteria

Inclusion Criteria for Healthy Subjects:

Male or female between 18 and 55 years of age, extremes included.
Subjects must have a body mass index (BMI) of 18.0 to 32.0 kg/m2, extremes included.

Inclusion Criteria for CHB Subjects (Parts 2 and 3):

Subjects must be 18 to 70 years of age, inclusive of extremes.
Subjects may have a BMI of 18.0 to 35.0 kg/m2, extremes included.
For virally suppressed subjects, must be currently receiving HBV NA treatment for ≥6 months prior to screening. For currently not treated or treatment naïve subjects, must have never received treatment OR have not been on treatment within 6 months prior to randomization

Exclusion Criteria for All Subjects:

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
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.
Subjects with a history of clinically significant drug allergy
Subject with current or history of clinically significant (as determined by the Investigator) skin disease requiring intermittent or chronic treatment
Excessive use of alcohol defined as regular consumption of

≥14 standard drinks/week for women and ≥21 standard drinks/week for men

Subjects with Hepatitis A, B, C, D, E or HIV-1/HIV-2 infection or acute infections such as SARS- CoV-2 infection

Exclusion Criteria for Healthy Volunteers (Part 1):

Unwilling to abstain from alcohol use for 48 hours prior to start of study through end of study follow up.
Subjects with renal dysfunction [e.g., estimated creatinine clearance <90 mL/min/1.73 m2 at screening, calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula]

Exclusion criteria for CHB subjects (Parts 2 and 3):

Subjects who are positive for anti-HBs antibodies.
Subject with any history or current evidence of hepatic decompensation such as: variceal bleeding, spontaneous bacterial peritonitis, ascites, hepatic encephalopathy, or active jaundice (within the last year).
History or current evidence of cirrhosis.
Subjects with liver fibrosis that is classified as Metavir Score ≥F3 liver disease
Subjects must have absence of signs of hepatocellular carcinoma

Contacts and Locations

Locations

	Site	City	Country
1	MBAL Sveta Sofia EOOD, Dept of Internal Medicine with Gastroenterology Section	Sofia	Bulgaria
2	PMSI Republican Clinical Hospital "t. Mosneaga", ARENSIA Exploratory Medicine Phase 1 Unit	Chisinau	Moldova, Republic of
3	New Zealand Clinical Research	Auckland	New Zealand
4	National Institute for Infection Diseases, ARENSIA Exploratory Medicine S.R.L.	Bucharest	Romania