A Study of ALG-010133 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single and Multiple Doses in Healthy Volunteers and CHB Subjects

Chronic Hepatitis B Clinical Trial

Official title:

A Phase 1, Double-blind, Randomized, Placebo-controlled, First-in-human Study of Subcutaneously Administered ALG-010133 to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single Ascending Doses (Part 1) and Multiple Ascending Doses in Healthy Volunteers (Part 2), and Multiple Doses in Subjects With Chronic Hepatitis B (Part 3)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04485663
• Other study ID #: ALG-010133-101
• Status: Terminated
• Phase: Phase 1
• Start date: August 17, 2020
• Est. completion date: March 8, 2022

Study information

• Verified date: March 2022
• Source: Aligos Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Randomized Study of ALG-010133 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single and Multiple Doses in Healthy Volunteers and CHB Subjects

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 103
• Est. completion date: March 8, 2022
• Est. primary completion date: March 8, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria for Healthy Subjects:

1. Male and Female between 18 and 55 years old

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

3. Subjects must be nonsmokers for at least 3 months prior to randomization

4. BMI 18.0 to 32.0 kg/m^2

5. Subjects must have a 12-lead ECG that meets protocol criteria

Inclusion Criteria for CHB Subjects:

1. Male and Female between 18 and 70 years old

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

3. BMI 18.0 to 35.0 kg/m^2

4. HBeAg-negative chronic hepatitis B or HBeAg-positive chronic hepatitis B and are currently receiving HBV NA treatment for =6 months prior to screening

5. Subjects must have a 12-lead ECG that meets protocol criteria

Exclusion Criteria for Healthy 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 units/week for women and =21 units/week for men

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

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

8. 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)

Exclusion Criteria for CHB 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 units/week for women and =21 units/week for men

6. Subjects with Hepatitis A, C, D, 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)

8. 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)

9. Subjects must have absence of signs of hepatocellular carcinoma

10. Subjects with history or current liver cirrhosis

11. Subjects positive for anti-HBs anitbodies

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• ALG-010133
Single or multiple doses of ALG-010133
• Placebo
Single or multiple doses of Placebo

Locations

Country	Name	City	State
China	The First Hospital of Jilin University	Changchun	Jilin
China	Nanfang Hospital of Southern Medical University	Guangzhou	Guangdong
Hong Kong	Queen Mary Hospital	Hong Kong
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Moldova, Republic of	PMSI Republican Clinical Hospital "T. Mosneaga", ARENSIA Exploratory Medicine Phase I Unit	Chisinau
New Zealand	ACS	Auckland
United Kingdom	King's College Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Aligos Therapeutics

Countries where clinical trial is conducted

China,  Hong Kong,  Korea, Republic of,  Moldova, Republic of,  New Zealand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 15 days for Part 1
Primary	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 29 days for Part 2
Primary	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 162 days for Part 3
Secondary	Maximum Plasma Concentration [Cmax]	Pharmacokinetic parameters of ALG-010133 in plasma	Predose (0 hours) up to 162 Days (3864 hours)
Secondary	Area under the concentration time curve [AUC]	Pharmacokinetic parameters of ALG-010133 in plasma	Predose (0 hours) up to 162 Days (3864 hours)
Secondary	Time to maximum plasma concentration [Tmax]	Pharmacokinetic parameters of ALG-010133 in plasma	Predose (0 hours) up to 162 Days (3864 hours)
Secondary	Half-time [t1/2]	Pharmacokinetic parameters of ALG-010133 in plasma	Predose (0 hours) up to 162 Days (3864 hours)
Secondary	Minimum Plasma Concentration [Cmin]	Pharmacokinetic parameters of ALG-010133 in plasma	Predose (0 hours) up to 162 Days (3864 hours)
Secondary	Change in HBsAg (reduction) from baseline through Day 78 in Multiple Dose HBV Infected Patients		Screening, Day -1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78