Chronic Hepatitis B
Conditions
Brief summary
The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of AHB-137 subcutaneous injection in healthy volunteers and in chronic hepatitis B (CHB) patients after single and multiple doses. In addition, the study will evaluate the initial antiviral efficacy of AHB-137 in CHB patients following a multiple dosing regimen.
Detailed description
This is a first-in-human study of AHB-137, consisting of four parts. Parts A and B are randomized, double-blinded, placebo-controlled studies designed to assess the safety, tolerability, pharmacokinetics of AHB-137 following subcutaneous injection in healthy volunteers at a 6:2 ratio of AHB-137 to placebo. Part A is a single-ascending dose (SAD) study, and Part B is a single-ascending dose (SAD) study, and Part B is a multiple dose (MD) study. Part C is an open label MD study with up to 6 CHB patients. Part D is a double blinded study in CHB patients at a 4:1 ratio to receive AHB-137 or placebo. Study advancement to subsequent parts/cohorts will require satisfactory interim reviews of available cumulative safety data by the Safety Review Committees (SRC), using the safety criteria and review procedures described in the protocol.
Interventions
AHB-137 will be administered
DRUGPlacebo
Placebo will be administered
Sponsors
AusperBio Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy participants are required to meet all the following inclusion criteria in order to be enrolled in the study: 1. 18-65 years old male or female. 2. Body Mass Index (BMI) between 19 to 35 kg/m2 (inclusive) and body weight equal to or over 45 kg. 3. Participants' COVID-19 PCR test should be negative during screening. 4. Participants' COVID-19 Rapid Antigen Test (RAT) should be negative at check-in. * CHB patients are required to meet all the following inclusion criteria in order to be enrolled in the study: 1. Have given written informed consent (signed and dated) and any authorizations required by local law and is able to comply with all study requirements. 2. Age 18 to 65 years old. 3. ALT ≤ 5 ULN for CHB patients recruited to Part C; ALT ≤ 2 ULN for CHB patients recruited to Part D. 4. CHB patients who have documented chronic HBV infection equal to or above 6 months prior to screening. Otherwise, CHB patients need to be HBsAg positive and IgM HBcAb negative. 5. CHB patients participating in Part D should have been on commercially available HBV OAV treatment(s) for at least 6 months with no change in regimen for 3 months prior to screening. HBV DNA under limit of quantification (LOQ) at Screening. 6. Both HBeAg positive and negative CHB patients can be recruited to Part C of the study. Only HBeAg negative CHB patients can be recruited to Part D of the study. 7. COVID-19 RAT test should be negative at check-in.
Exclusion criteria
* Healthy participants are required to not meet any of the following
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of Participants With Treatment-Emergent Adverse Events (TEAEs) in Healthy Volunteers | Up to 30 days for SAD, up to 113 days for MD |
| Proportion of Participants With Treatment-Emergent Adverse Events (TEAEs) in CHB patients | Up to 204 days for MD |
Secondary
| Measure | Time frame |
|---|---|
| The pharmacokinetic profile of AHB-137: the maximum observed plasma concentration (Cmax) of AHB-137 | Up to 30 days for SAD; up to 204 days for MD |
| The pharmacokinetic profile of AHB-137: time of observed maximal concentration (Tmax) of AHB-137 | Up to 30 days for SAD; up to 204 days for MD |
| The pharmacokinetic profile of AHB-137: areas under the concentration time curve (AUC) of AHB-137 | Up to 30 days for SAD; up to 204 days for MD |
| The pharmacokinetic profile of AHB-137: mean residence time (MRT) of AHB-137 | Up to 30 days for SAD; up to 204 days for MD |
| The anti-HBV efficacy of AHB-137: evaluate the change in serum HBsAg (log10 IU/mL) from baseline. | Up to 204 days |
| The pharmacokinetic profile of AHB-137: apparent subcutaneous plasma clearance (CL/F) of AHB-137 | Up to 30 days for SAD; up to 204 days for MD |
| The pharmacokinetic profile of AHB-137: amount of AHB-137 excreted in urine (Ae) | Day 1-4 for SAD; Day 1-4 and Day 22-25 for MD |
| The pharmacokinetic profile of AHB-137: renal clearance (CLr) of AHB-137 | Day 1-4 for SAD; Day 1-4 and Day 22-25 for MD |
| The pharmacokinetic profile of AHB-137: terminal half-life (t1/2) of AHB-137 | Up to 30 days for SAD; up to 204 days for MD |
| The anti-HBV efficacy of AHB-137: evaluate the expression of HBsAb in serum. | Up to 204 days |
Countries
Hong Kong, New Zealand, Taiwan, United States
Outcome results
None listed