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
Primary Purpose
Chronic Hepatitis B
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ALG-125755
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis B
Eligibility Criteria
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
Sites / Locations
- MBAL Sveta Sofia EOOD, Dept of Internal Medicine with Gastroenterology SectionRecruiting
- PMSI Republican Clinical Hospital "t. Mosneaga", ARENSIA Exploratory Medicine Phase 1 UnitRecruiting
- New Zealand Clinical ResearchRecruiting
- National Institute for Infection Diseases, ARENSIA Exploratory Medicine S.R.L.Recruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
ALG-125755
Placebo
Arm Description
Subcutaneous injections of ALG-125755 in HV or CHB subjects, up to 6 injections over the course of up to 72 weeks
Subcutaneous injections of placebo in HV or CHB subjects, up to 6 injections over the course of up to 72 weeks
Outcomes
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
Incidence and severity of treatment emergent adverse events as assessed by DAIDS v2.1
Incidence and severity of treatment emergent adverse events as assessed by DAIDS v2.1
Secondary Outcome Measures
Maximum plasma concentration (Cmax)
Pharmacokinetic parameters of ALG-125755 in plasma
Area under the concentration time curve [AUC]
Pharmacokinetic parameters of ALG-125755 in plasma
Time to maximum plasma concentration [Tmax]
Pharmacokinetic parameters of ALG-125755 in plasma
Antiviral activity of ALG-125755 as measured by quantitative changes in serum
Pharmacokinetic parameters of ALG-125755 in plasma
Minimum plasma concentration (Cmin)
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05561530
Brief Title
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
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)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 7, 2022 (Actual)
Primary Completion Date
July 1, 2025 (Anticipated)
Study Completion Date
December 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aligos Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. 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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ALG-125755
Arm Type
Experimental
Arm Description
Subcutaneous injections of ALG-125755 in HV or CHB subjects, up to 6 injections over the course of up to 72 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subcutaneous injections of placebo in HV or CHB subjects, up to 6 injections over the course of up to 72 weeks
Intervention Type
Drug
Intervention Name(s)
ALG-125755
Intervention Description
single or multiple doses of ALG-125755
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
single or multiple doses of placebo
Primary Outcome Measure Information:
Title
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
Time Frame
Up to 32 days for Part 1
Title
Incidence and severity of treatment emergent adverse events as assessed by DAIDS v2.1
Time Frame
Up to 52 days for Part 2
Title
Incidence and severity of treatment emergent adverse events as assessed by DAIDS v2.1
Time Frame
Up to 616 days for Part 3
Secondary Outcome Measure Information:
Title
Maximum plasma concentration (Cmax)
Description
Pharmacokinetic parameters of ALG-125755 in plasma
Time Frame
Predose (0 hours) up to 616 days
Title
Area under the concentration time curve [AUC]
Description
Pharmacokinetic parameters of ALG-125755 in plasma
Time Frame
Predose (0 hours) up to 616 days
Title
Time to maximum plasma concentration [Tmax]
Description
Pharmacokinetic parameters of ALG-125755 in plasma
Time Frame
Predose (0 hours) up to 616 days
Title
Antiviral activity of ALG-125755 as measured by quantitative changes in serum
Description
Pharmacokinetic parameters of ALG-125755 in plasma
Time Frame
Predose (0 hours) up to 616 days
Title
Minimum plasma concentration (Cmin)
Description
Pharmacokinetic parameters of ALG-125755 in plasma
Time Frame
Predose (0 hours) up to 616 days
Title
Change in HBsAg from baseline through up to 112 days from last dose in multiple dose HBV infected subjects
Time Frame
screening to up to 112 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Facility Information:
Facility Name
MBAL Sveta Sofia EOOD, Dept of Internal Medicine with Gastroenterology Section
City
Sofia
Country
Bulgaria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniel Iliev
Phone
+359 878 334 915
Email
daniel.iliev@arensia-em.com
Facility Name
PMSI Republican Clinical Hospital "t. Mosneaga", ARENSIA Exploratory Medicine Phase 1 Unit
City
Chisinau
Country
Moldova, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexei Haceatraian
Phone
373 78 886638
Email
alexei.haceatrean@arensia-em.com
Facility Name
New Zealand Clinical Research
City
Auckland
Country
New Zealand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+64 9 373 3474
Email
axis@nzcr.co.nz
Facility Name
National Institute for Infection Diseases, ARENSIA Exploratory Medicine S.R.L.
City
Bucharest
Country
Romania
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ambra Stoiu
Phone
+40 728 169 609
Email
ambra.stoiu@arensia-em.com
12. IPD Sharing Statement
Learn more about this trial
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
We'll reach out to this number within 24 hrs