A Study of ALG-000184 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single and Multiple Doses in Healthy Volunteers and CHB Subjects

• Sponsor: Aligos Therapeutics (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04536337
• Collaborator: (none)
• Enrollment: 156
• Locations: 6
• Arms: 2
• Anticipated Duration (Months): 20.3
• Patients Per Site: 26
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

A Randomized Study of ALG-000184 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single and Multiple Doses in Healthy Volunteers and CHB Subjects

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis B	Drug: ALG-000184; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 156 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Double-Blind, Randomized, Placebo-Controlled, First-in-Human Study of Orally Administered ALG-000184 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)
• Actual Study Start Date: Oct 22, 2020
• Anticipated Primary Completion Date: Jul 1, 2022
• Anticipated Study Completion Date: Jul 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ALG-000184 Oral tablet(s) of ALG-000184 in HV or CHB subjects once daily for up to 4 weeks	Drug: ALG-000184; Single or multiple doses of ALG-000184
Placebo Comparator: Placebo Oral tablet(s) of placebo in HV or CHB subjects once daily for up to 4 weeks	Drug: Placebo; Single or multiple doses of Placebo

Outcome Measures

Primary Outcome Measures

1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [up to 8 days for Part 1]

   The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1

2. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [up to 21 days for Part 2]

   The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1

3. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [up to 112 days for Part 3]

   The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1

Secondary Outcome Measures

1. Maximum Plasma Concentration [Cmax] [Predose (0 hours) up to 28 Days]

   Pharmacokinetic parameters of ALG-000184 in plasma

2. Area under the concentration time curve [AUC] [Predose (0 hours) up to 28 Days]

   Pharmacokinetic parameters of ALG-000184 in plasma

3. Time to maximum plasma concentration [Tmax] [Predose (0 hours) up to 28 Days]

   harmacokinetic parameters of ALG-000184 in plasma

4. Half-time [t1/2] [Predose (0 hours) up to 28 Days]

   Pharmacokinetic parameters of ALG-000184 in plasma

5. Minimum Plasma Concentration [Cmin] [Predose (0 hours) up to 28 Days]

   Pharmacokinetic parameters of ALG-000184 in plasma

6. Change in HBV DNA (reduction) from baseline through Day 28 in Multiple Dose HBV Infected Patients [Screening, Day -1 to Day 28]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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 65 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

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

6. Subjects must be treatment naïve or currently not treated within 6 months prior of randomization

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. Excessive use of alcohol defined as regular consumption of ≥14 units/week for women and ≥21 units/week for men

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

6. Subjects with Hepatitis A, B, 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)

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. Excessive use of alcohol defined as regular consumption of ≥14 units/week for women and ≥21 units/week for men

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

6. Subjects with renal dysfunction (e.g., estimated creatinine clearance <70 mL/min/1.73 m^2 at screening, calculated by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula)

7. 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)

8. Subjects must have absence of signs of hepatocellular carcinoma

9. Subjects positive for anti-HBs antibodies

10. History or current evidence of cirrhosis

11. Subjects with liver fibrosis that is classified as Metavir Score ≥F3 liver disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nanfang Hospital of Southern Medical University	Guangzhou	Guangdong	China
2	The First Hospital of Jilin University	Changchun	Jilin	China	130021
3	Queen Mary Hospital	Hong Kong		Hong Kong
4	PMSI Republican Clinical Hospital "T. Mosneaga", ARENSIA Exploratory Medicine Phase I Unit	Chisinau		Moldova, Republic of
5	ACS	Auckland		New Zealand
6	King's College Hospital	London		United Kingdom

Sponsors and Collaborators

• Aligos Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Aligos Therapeutics
• ClinicalTrials.gov Identifier: NCT04536337
• Other Study ID Numbers: ALG-000184-201
• First Posted: Sep 2, 2020
• Last Update Posted: Sep 14, 2021
• Last Verified: Sep 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic

Study Results

No Results Posted as of Sep 14, 2021