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

Chronic Hepatitis B Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05561530
• Other study ID #: ALG-125755-501
• Status: Terminated
• Phase: Phase 1
• Start date: October 7, 2022
• Est. completion date: June 15, 2023

Study information

• Verified date: March 2024
• Source: Aligos Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 57
• Est. completion date: June 15, 2023
• Est. primary completion date: June 15, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria for All Subjects:

1. Female subjects must have a negative serum pregnancy test at screening

2. Subjects must have a 12-lead electrocardiogram (ECG) that meets the protocol criteria

Inclusion Criteria for Healthy Subjects:

1. Male or female between 18 and 55 years of age, extremes included.

2. 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):

1. Subjects must be 18 to 70 years of age, inclusive of extremes.

2. Subjects may have a BMI of 18.0 to 35.0 kg/m2, extremes included.

3. 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:

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. Subject with current or history of clinically significant (as determined by the Investigator) skin disease requiring intermittent or chronic treatment

5. Excessive use of alcohol defined as regular consumption of

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

6. 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):

1. Unwilling to abstain from alcohol use for 48 hours prior to start of study through end of study follow up.

2. 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):

1. Subjects who are positive for anti-HBs antibodies.

2. 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).

3. History or current evidence of cirrhosis.

4. Subjects with liver fibrosis that is classified as Metavir Score =F3 liver disease

5. Subjects must have absence of signs of hepatocellular carcinoma

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• ALG-125755
single or multiple doses of ALG-125755
• Placebo
single or multiple doses of placebo

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Aligos Therapeutics

Countries where clinical trial is conducted

Bulgaria,  Moldova, Republic of,  New Zealand,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Incidence and severity of treatment emergent adverse events as assessed by DAIDS v2.1		Up to 52 days for Part 2
Primary	Incidence and severity of treatment emergent adverse events as assessed by DAIDS v2.1		Up to 616 days for Part 3
Secondary	Maximum plasma concentration (Cmax)	Pharmacokinetic parameters of ALG-125755 in plasma	Predose (0 hours) up to 616 days
Secondary	Area under the concentration time curve [AUC]	Pharmacokinetic parameters of ALG-125755 in plasma	Predose (0 hours) up to 616 days
Secondary	Time to maximum plasma concentration [Tmax]	Pharmacokinetic parameters of ALG-125755 in plasma	Predose (0 hours) up to 616 days
Secondary	Antiviral activity of ALG-125755 as measured by quantitative changes in serum	Pharmacokinetic parameters of ALG-125755 in plasma	Predose (0 hours) up to 616 days
Secondary	Minimum plasma concentration (Cmin)	Pharmacokinetic parameters of ALG-125755 in plasma	Predose (0 hours) up to 616 days
Secondary	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