A Study Evaluating AHB-137 in Healthy Participants and Participants With Chronic Hepatitis B

Sponsor

Ausper Biopharma Co., Ltd. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05717686

Collaborator

(none)

Enrollment

Location

Arms

21.9

Anticipated Duration (Months)

2.7

Patients Per Site Per Month

Study Details

Study Description

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 antiviral efficacy of AHB-137 in CHB patients following a multiple dosing regimen.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis B	Drug: AHB-137 injection Drug: Placebo	Phase 1

Detailed Description

This study is a four-part and first-in-human study of AHB-137. Parts A and B are randomized, double-blinded, placebo-controlled studies to evaluate the safety, tolerability, pharmacokinetics of AHB-137 following subcutaneous injection in healthy volunteers. Part A is a single-ascending dose (SAD) study and part B is a multiple dose (MD) study. Healthy volunteers will be enrolled and randomized to 6:2 ratio to receive AHB-137 or placebo. Part C and part D are multiple dose studies to assess the safety, tolerability, pharmacokinetics, and antiviral efficacy of AHB-137 in at least 16 CHB patients in multiple centers across multiple regions.

To ensure the objective assessment of the safety and tolerability of AHB-137 in healthy volunteers, study participant, care provider, investigator and clinical outcomes assessor will be blinded to the treatment assignment (AHB-137 vs 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of AHB-137 With Single Ascending Doses and Multiple Ascending Doses in Healthy Volunteers and Chronic Hepatitis B Patients

Anticipated Study Start Date :

Feb 2, 2023

Anticipated Primary Completion Date :

Aug 31, 2024

Anticipated Study Completion Date :

Nov 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: SAD in healthy participants Single ascending doses of AHB-137 by subcutaneous (SC) injection in healthy participants. Cohort 1, 2, 3, 4 will be dosed at 100 mg, 200 mg, 300 mg and 450 mg , respectively.	Drug: AHB-137 injection AHB-137 will be administered Drug: Placebo Placebo will be administered
Experimental: Part B: MD in healthy participants Part B: Multiple doses of 300 mg AHB-137 by subcutaneous (SC) injection in healthy participants	Drug: AHB-137 injection AHB-137 will be administered Drug: Placebo Placebo will be administered
Experimental: Part C: MD in CHB patients (open label) Part C: Multiple doses of 300 mg AHB-137 by subcutaneous (SC) injection in CHB patients	Drug: AHB-137 injection AHB-137 will be administered
Experimental: Part D: MD in CHB patients in multiple centers Part D: at least two adaptive cohorts will be studied to assess multiple doses of less than 300 mg AHB-137 by subcutaneous (SC) injection in CHB patients (Multiple centers across multiple regions). The exact dose will be determined based on early cohort results.	Drug: AHB-137 injection AHB-137 will be administered

Outcome Measures

Primary Outcome Measures

Proportion of Participants With Treatment-Emergent Adverse Events (TEAEs) in Healthy Volunteers [Up to 30 days for SAD, up to 113 days for MAD]
Proportion of Participants With Treatment-Emergent Adverse Events (TEAEs) in CHB patients [Up to 113 days for MD]

Secondary Outcome Measures

The anti-HBV efficacy of AHB-137: evaluate the level (IU/mL) of HBsAg in serum on Day 1 (baseline), 15, 23, 29, 36, 50, 71 and 113 in CHB patients treated with AHB-137 [Up to 113 days]
The anti-HBV efficacy of AHB-137: evaluate the level (copies/mL) of HBV DNA in serum on Day 1 (baseline), 15, 23, 29, 36, 50, 71 and 113 in CHB patients treated with AHB-137 [Up to 113 days]
The anti-HBV efficacy of AHB-137: evaluate the level (mIU/mL) of HBsAb in serum on Day 1 (baseline), 15, 23, 29, 36, 50, 71 and 113 in CHB patients treated with AHB-137 [Up to 113 days]
The anti-HBV efficacy of AHB-137: evaluate the level (IU/mL) of HBeAg in serum on Day 1 (baseline), 15, 23, 29, 36, 50, 71 and 113 in CHB patients treated with AHB-137 [Up to 113 days]
The anti-HBV efficacy of AHB-137: evaluate the level (mIU/mL) of HBeAb in serum on Day 1 (baseline), 15, 23, 29, 36, 50, 71 and 113 in CHB patients treated with AHB-137 [Up to 113 days]
The anti-HBV efficacy of AHB-137: evaluate the level (copies/mL) of HBV pgRNA in serum on Day 1 (baseline), 15, 29, 50 and 113 in CHB patients treated with AHB-137 [Up to 113 days]
The anti-HBV efficacy of AHB-137: evaluate the level (IU/mL) of HBcrAg in serum on Day 1 (baseline), 15, 29, 50 and 113 in CHB patients treated with AHB-137 [Up to 113 days]
The pharmacokinetic profile of AHB-137: the maximum observed plasma concentration (Cmax) of AHB-137 [Up to 30 days for SAD; up to 113 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 113 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 113 days for MD]
The pharmacokinetic profile of AHB-137: mean residence time (MRT) of AHB-137 [Up to 30 days for SAD; up to 113 days for MD]
The pharmacokinetic profile of AHB-137: terminal half-life (t1/2) of AHB-137 [Up to 30 days for SAD; up to 113 days for MD]
The pharmacokinetic profile of AHB-137: apparent subcutaneous plasma clearance (CL/F) of AHB-137 [Up to 30 days for SAD; up to 113 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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy participants are required to meet all the following inclusion criteria in order to be enrolled in the study:

18-65 years old male or female.
Body Mass Index (BMI) between 19 to 35 kg/m2 (inclusive) and body weight equal to or over 45 kg.
Healthy female volunteers cannot be pregnant at the time of recruiting and during the study. Healthy female volunteers with childbearing potential must remain abstinent or use two methods of contraception with their partner, one of which must be a barrier method (E.g. condom), for the duration of the study and for at least 3 months after the last dose of study-drug.
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm.
Participants' COVID-19 PCR test should be negative during screening.
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:

Have given written informed consent (signed and dated) and any authorizations required by local law and is able to comply with all study requirements.
Age 18 to 65 years old.
ALT < 5 ULN.
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.
Female patients cannot be pregnant at the time of recruiting and during the study. Healthy female volunteers with childbearing potential must remain abstinent or use two methods of contraception with their partner, one of which must be a barrier method (E.g. condom), for the duration of the study and for at least 3 months after the last dose of study-drug. For male patients: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm.
Participants receiving stable nucletos(t)ide analogue (NA) therapy were expected to continue NA therapy during the trial; participants not receiving NA therapy at the time of trail entry were expected to continue without NA during the trail.
COVID-19 PCR test should be negative during screening.
COVID-19 RAT test should be negative at check-in.

Exclusion Criteria:

Healthy participants are required to not meet any of the exclusion criteria in order to be enrolled in the study:

Pregnant (positive pregnancy test) or lactating women. Male participants without using proper contraceptives (e.g. condom) with partners who are pregnant or lactating.
History or symptoms of any clinically significant gastrointestinal, renal, hepatic, bronchopulmonary, neurological, psychiatric, cardio-vascular, endocrinological, hematological or allergic disease, metabolic disorder, cancer or cirrhosis.
Personal history of congenital long QT syndrome or family history of sudden cardiac death.
Any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug, or multiple drug allergies (non-active hay fever is acceptable).
Any clinically significant concomitant diseases or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study.
Clinically relevant electrocardiogram (ECG) abnormalities on screening ECG.
ECG with QRS and/or T-wave judged to be unfavorable for a consistently accurate QT measurement.
Creatinine clearance (CrCl) cutoff = 80 ml/min (using the Cockcroft-Gault formula).
Positive test at screening of any of the following: hepatitis A (HAV IgM Ab), hepatitis B (HBsAg), hepatitis C (HCV RNA or HCV Ab), human immunodeficiency virus 1 and 2 (HIV Ab), or TP-Ab.
Any other clinically significant abnormalities in laboratory test results at screening. In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility.
History of bleeding diathesis or coagulopathy.

CHB patients are required to not meet any of the exclusion criteria in order to be enrolled in the study:

History of liver cirrhosis and/or evidence of cirrhosis as determined by any 1 of the following:
Liver biopsy (i.e., Metavir Score F4) within 2 years of screening, or
FibroScan > 12 KPa, within 12 months of screening, or
AST-to-Platelet Index (APRI) > 2 and FibroSure result > 0.7 within 12 months of screening.

For patients without a test for cirrhosis in the above timeframes, FibroScan, or APRI and FibroSure, may be performed during the screening period to rule out cirrhosis History of liver failure as evidenced by ascites, hepatic encephalopathy, and/or gastric or esophageal varices.

History of liver disease other than hepatitis B.
Co-infection with TP, HCV, HIV, or hepatitis D virus (HDV).
Body mass index >35 kg/m2 .
History or suspected presence of vasculitis .
Diagnosed hepatocellular carcinoma or suspected hepatocellular carcinoma as evidenced by screening alpha-fetoprotein ≥200 ng/mL. If the screening alpha-fetoprotein is ≥50 ng/mL and <200 ng/mL, the absence of liver mass must be documented by imaging within 6 months before randomization.
Clinically relevant electrocardiogram (ECG) abnormalities on screening ECG.
Screening laboratory results as follows, or any other clinically significant abnormalities in screening laboratory values that would render a patient unsuitable for inclusion.
ALT or Aspartate-amino-transferase (AST) > 5 x ULN
Total bilirubin >1.5 x ULN
Serum albumin <3.5 g/dL
International normalized ratio >1.2
Platelet count <140 k/mm3
Hemoglobin <12.0 g/dL for males and <11.0 g/dL for females
White blood cell count <3.0 k/mm3
Serum creatinine >1.1 x ULN
Urine protein/creatinine ratio ≥0.2 mg/mg. In the event of a ratio above this threshold, eligibility may be confirmed by a quantitative total urine protein measurement of <150 mg/24 hour
Positive test (including trace) for blood on urinalysis. In the event of a positive test, eligibility may be confirmed with urine microscopy showing <5 red blood cells per high power field
Clinically significant abnormalities aside from chronic HBV infection in medical history (e.g., previous acute coronary syndrome within 6 months of screening, major surgery within 3 months of screening, uncontrolled diabetes) or physical examination.
History of bleeding diathesis or coagulopathy.
History of extrahepatic disorders possibly related to HBV immune complexes (e.g., glomerulonephritis, polyarteritis nodosa) .
Active infection other than HBV, requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New Zealand Clinical Research	Grafton	Auckland	New Zealand	1010

Sponsors and Collaborators

Ausper Biopharma Co., Ltd.

Investigators

Principal Investigator: Ed Gane, University of Auckland, New Zealand

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Ausper Biopharma Co., Ltd.

ClinicalTrials.gov Identifier:

NCT05717686

Other Study ID Numbers:

AB-10-8001

First Posted:

Feb 8, 2023

Last Update Posted:

Feb 8, 2023

Last Verified:

Jan 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 8, 2023