Clinical trial NCT04485663: A Study of ALG-010133 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single and Multiple Doses in Healthy Volunteers and CHB Subjects
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Chronic Hepatitis B
Lead sponsor: Aligos Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-07-24
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: up to 15 days for Part 1
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: up to 29 days for Part 2
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: up to 162 days for Part 3
Secondary outcomes:
measure: Maximum Plasma Concentration [Cmax]
timeFrame: Predose (0 hours) up to 162 Days (3864 hours)
measure: Area under the concentration time curve [AUC]
timeFrame: Predose (0 hours) up to 162 Days (3864 hours)
measure: Time to maximum plasma concentration [Tmax]
timeFrame: Predose (0 hours) up to 162 Days (3864 hours)
measure: Half-time [t1/2]
timeFrame: Predose (0 hours) up to 162 Days (3864 hours)
measure: Minimum Plasma Concentration [Cmin]
timeFrame: Predose (0 hours) up to 162 Days (3864 hours)
measure: Change in HBsAg (reduction) from baseline through Day 78 in Multiple Dose HBV Infected Patients
timeFrame: Screening, Day -1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Chisinau
country: Moldova, Republic of
facility: PMSI Republican Clinical Hospital "T. Mosneaga", ARENSIA Exploratory Medicine Phase I Unit
city: Auckland
country: New Zealand
facility: ACS
city: London
country: United Kingdom
facility: King's College Hospital
Study officials:
References: