Hepatitis B, Chronic
Conditions
Brief summary
The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of AHB-137 subcutaneous injection in healthy participants after single and multiple doses, and evaluate the preliminary efficacy of AHB-137 in CHB participants after up to 24 weeks of treatment as a proof-of-concept.
Detailed description
This study is a three-part study of AHB-137, including Part Ia, Part Ib and Part IIa. Part Ia evaluates the safety, tolerability, pharmacokinetics of AHB-137 following single-ascending doses (SAD) and multiple-ascending doses (MAD) in healthy participants. Part Ib is a multiple-dose study to assess the safety, tolerability, pharmacokinetics, and initial efficacy of AHB-137 in CHB participants following weekly dosing for 4 weeks with two loading doses in the first two weeks. Part IIa is a multiple-dose study to evaluate the preliminary efficacy, safety and pharmacokinetics of AHB-137 in CHB participants following weekly dosing for 24 weeks with two loading doses in the first two weeks.
Interventions
AHB-137 injection will be administered subcutaneously.
DRUGPlacebo
Placebo will be administered subcutaneously.
Sponsors
Ausper Biopharma Co., Ltd.
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 (Part Ia): 1. The participants voluntarily participate in the study, and sign the Informed Consent Form (ICF) prior to screening; 2. The participants are able to comply with all the protocol requirements; 3. The participants (and partners) are willing to take effective contraceptive measures from the screening until at least 6 months after the last dosing; 4. Male or female aged 18-55 when signing ICF; 5. Body Mass Index (BMI) between 18 to 28 kg/m2 (inclusive) and body weight equal to or over 50 kg for male and 45 kg for female; 6. Vital signs and physical examination are normal, or abnormal values are not clinically significant. * CHB participants are required to meet all the following inclusion criteria in order to be enrolled in the study (Part Ib and part IIa): 1. The participants voluntarily participate in the study, and sign the Informed Consent Form (ICF) prior to screening; 2. The participants are able to comply with all the protocol requirements; 3. The participants (and partners) are willing to take effective contraceptive measures from the screening until at least 6 months after the last dosing; 4. Male or female aged 18-65 when signing ICF; 5. Body Mass Index (BMI) between 18 to 32 kg/m2 (inclusive) and body weight equal to or over 45 kg for male and 40 kg for female; 6. participants who have documented chronic HBV infection equal to or above 6 months prior to screening. 7. Stable treatment of HBeAg negative CHB participants; 8. Currently receiving single-agent treatment with stable NAs (TDF, TAF, or ETV) for at least 6 months and no changes in the NAs treatment regimen are planned during the trial; 9. Serum ALT≤2×ULN, HBV DNA \< 100 IU/mL. Dose increasing stage of Ib: 100 IU/mL \<HBsAg≤1000 IU/mL; Dose expansion stage of Ib: 1000 IU/ml \< HBsAg≤3000 IU/mL at screening; IIa phase: 100 IU/ml \< HBsAg≤ 3000 IU/mL at screening; 10. Participants who are willing and able to terminate NA treatment according to the protocol in IIa stage.
Exclusion criteria
* Healthy participants are required to not meet any of the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of healthy participants with TEAEs, SAEs | Up to 30 days for SAD; up to 113 days for MAD |
| Number of healthy participants with clinically significant changes in laboratory parameters | Up to 30 days for SAD; up to 113 days for MAD |
| Number of healthy participants with clinically significant changes in vital signs | Up to 30 days for SAD; up to 113 days for MAD |
| Number of healthy participants with clinically significant changes in ECG | Up to 30 days for SAD; up to 113 days for MAD |
| Number of healthy participants with ADA | Up to 30 days for SAD; up to 113 days for MAD |
| The pharmacokinetic profile of AHB-137 in healthy participants: the Cmax of AHB-137 | Up to 30 days for SAD; up to 113 days for MAD |
| The pharmacokinetic profile of AHB-137 in healthy participants: Tmax of AHB-137 | Up to 30 days for SAD; up to 113 days for MAD |
| The pharmacokinetic profile of AHB-137 in healthy participants: AUC of AHB-137 | Up to 30 days for SAD; up to 113 days for MAD |
| The pharmacokinetic profile of AHB-137 in healthy participants: t1/2 of AHB-137 | Up to 30 days for SAD; up to 113 days for MAD |
| Number of CHB participants with TEAEs, SAEs | Up to 113 days for Ib |
| Number of CHB participants with clinically significant changes in laboratory parameters | Up to 113 days for Ib |
| Number of CHB participants with clinically significant changes in vital signs | Up to 113 days for Ib |
| Number of CHB participants with clinically significant changes in ECG | Up to 113 days for Ib |
| Proportion of participants achieving HBsAg lower than LLOQ (0.05 IU/mL) and HBV DNA lower than LLOQ at the end of treatment with AHB-137, regardless of whether HBsAg seroconversion is observed | At week 24 for IIa |
Secondary
| Measure | Time frame |
|---|---|
| The anti-HBV efficacy of AHB-137 in CHB participants: evaluate the serum levels of HBV DNA, HBsAg, HBV RNA, HBsAb, HBeAb | Up to 113 days for Ib; Up to 72 weeks for IIa |
| Evaluate the serum levels of sensitive HBsAg (LLOQ ≤0.005 IU/mL) and HBcrAg. | Up to 72 weeks for IIa |
| The pharmacokinetic profile of AHB-137 in CHB participants: the Cmax of AHB-137 | up to 113 days for Ib; Up to 48 weeks for IIa |
| The pharmacokinetic profile of AHB-137 in CHB participants: Tmax of AHB-137 | up to 113 days for Ib; Up to 48 weeks for IIa |
| The pharmacokinetic profile of AHB-137 in CHB participants: AUC of AHB-137 | up to 113 days for Ib; Up to 48 weeks for IIa |
| The pharmacokinetic profile of AHB-137 in CHB participants: t1/2 of AHB-137 | up to 113 days for Ib; Up to 48 weeks for IIa |
| Number of CHB participants with ADA | Up to113 days for Ib; Up to 48 weeks for IIa |
| Number of CHB participants with TEAEs, SAEs | Up to 72 weeks for IIa |
| Number of CHB participants with clinically significant changes in laboratory parameters, ECG, and vital signs | Up to 72 weeks for IIa |
| Proportion of CHB participants achieving HBsAg lower than LLOQ and HBV DNA lower than LLOQ during or after 24-week treatment, regardless of whether HBsAg seroconversion is observed | Up to 72 weeks for IIa |
| Proportion of CHB participants meeting the discontinuation criteria for NA treatment | At 48 weeks for IIa |
| Sequencing of the Viral DNA and/or viral RNA analysis for detection of drug resistance in the target region of AHB-137 | Up to 113 days for Ib; Up to 72 weeks for IIa |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORYanhua Ding
The First Hospital of Jilin University
PRINCIPAL_INVESTIGATORJunqi Niu
The First Hospital of Jilin University
Outcome results
None listed