A Study Evaluating ABI-H0731+ Entecavir vs Entecavir Alone for the Treatment of Viremic HBeAg-positive Participants With Chronic Hepatitis B Virus Infection (cHBV)

• Sponsor: Assembly Biosciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03577171
• Collaborator: (none)
• Enrollment: 25
• Locations: 12
• Arms: 2
• Actual Duration (Months): 12.1
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if ABI-H0731 given in combination with a standard of care (SOC) entecavir (ETV) is safe and effective in participants with chronic hepatitis B infection (cHBV)

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis B	Drug: ABI-H0731; Drug: SOC ETV; Drug: Placebo Oral Tablet	Phase 2

Detailed Description

This is a Phase 2a, multi-center, double-blind, placebo-controlled study evaluating ABI-H0731+ ETV vs ETV alone for the treatment of viremic hepatitis B "e" antigen (HBeAg)-positive participants with cHBV.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2a, Multi-center, Double-blind, Placebo-controlled Study Evaluating ABI-H0731+ Entecavir vs Entecavir Alone for the Treatment of Viremic HBeAg-positive Patients With Chronic Hepatitis B
• Actual Study Start Date: Jun 19, 2018
• Actual Primary Completion Date: Jun 21, 2019
• Actual Study Completion Date: Jun 21, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ABI-H0731 + SOC ETV Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary.	Drug: ABI-H0731; Participants will receive 300mg QD of ABI-H0731 tablets orally.; Drug: SOC ETV; Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.; Other Names: Entecavir
Experimental: Placebo + SOC ETV Participants with cHBV who are currently not being treated will receive matching placebo along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary.	Drug: SOC ETV; Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.; Other Names: Entecavir ; Drug: Placebo Oral Tablet; Participants will receive matching QD placebo tablets orally.

Outcome Measures

Primary Outcome Measures

1. Change in Mean log10 HBV DNA From Baseline (Day 1) to Week 12 or Week 24 on ABI H0731 + SOC ETV as Compared to Placebo + SOC ETV [Baseline, Week 12, and Week 24]

   Hepatitis B virus (HBV) DNA was measured using COBAS TaqMan Version 2.0. The lower limit of quantitation (LLOQ) was 20 IU/mL and the limit of detection (LOD) was 10 IU/mL.

Secondary Outcome Measures

1. Number of Participants One or More Adverse Events [Up to Follow-up (maximum up to Week 36)]

2. Number of Participants With Premature Study Discontinuation [Up to Follow-up (maximum up to Week 36)]

3. Number of Participants With One or More Abnormal Safety Laboratory Result [Up to Week 36]

4. Number of Participants With a Clinically-significant Electrocardiogram Abnormality [Up to Week 24]

5. Number of Participants With a Clinically-significant Change in Vital Signs [Baseline and up to Week 24]

   Vital signs assessed were body temperature, respiratory rate, and pulse rate

6. Number of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Have Normal ALT at Week 24 on ABI-H0731 + SOC ETV as Compared to Placebo + SOC ETV [Baseline to Week 24]

7. Number of Participants With a Decline in Viral DNA to Below Limit of Quantitation on ABI-H0731 + SOC ETV as Compared to Placebo + SOC ETV [Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24]

   HBV DNA was measured using COBAS TaqMan Version 2.0. The LLOQ was 20 IU/mL and the LOD was 10 IU/mL. The number of participants with HBV DNA below the limit of quantitation (<20 IU/mL) and target detected (≥10 IU/mL) was assessed.

8. Median Time to Viral Suppression, Defined as HBV DNA <20 IU/mL, on ABI-H0731 + ETV as Compared to Placebo + ETV [Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24]

   Median time to viral suppression will be calculated and evaluated between participants on ABI-H0731 + ETV as compared to placebo + ETV.

9. Number of Participants With Emergence of Resistant HBV Variants on ABI-H0731 + SOC ETV as Compared to Placebo + SOC ETV [Up to Week 36]

   Emergence of a resistant HBV variant was defined as an increase of ≥1 log10 IU/mL from the nadir in HBV DNA.

10. Trough Levels of ABI-H0731 on ABI-H0731 + SOC ETV Therapy [Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24]

11. Trough Levels of ETV on ABI-H0731 + ETV Therapy as Compared With Placebo + ETV Therapy [Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24]

12. Trough to Peak Ratios of ABI-H0731 on ABI-H0731 + ETV Therapy [Baseline, Weeks 2, 4, 12, and 24]

13. Trough to Peak Ratios of ETV on ABI-H0731 + ETV Therapy as Compared With Placebo + ETV Therapy [Baseline, Weeks 2, 4, 12, 24, and 28]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Male or female between ages 18 and 70 years

• HBeAg-positive at screening

• In good general health except for cHBV

• HBV viral load ≥2×105 IU/mL

• Hepatitis B surface antigen (HBsAg) >1000 IU/mL at screening

Key Exclusion Criteria:

• Any prior treatment with lamivudine or telbivudine, previous treatment with an investigational agent for HBV other than ABI-H0731; or any other SOC treatment for >4 weeks

• Co-infection with HIV, hepatitis C virus (HCV), hepatitis E virus (HEV) or hepatitis D virus (HDV)

• History or evidence of hepatic decompensation (including gastrointestinal bleeding or esophageal varices) at any time prior to or at time of screening

• Clinically significant cardiac or pulmonary disease, chronic or recurrent renal or urinary tract disease, liver disease other than HBV, endocrine disorder, autoimmune disorder, diabetes mellitus requiring treatment with insulin or hypoglycemic agents, neuromuscular, musculoskeletal, or mucocutaneous conditions requiring frequent treatment, seizure disorders requiring treatment, or other medical conditions requiring frequent medical management or pharmacologic or surgical treatment that in the opinion of the Investigator or the Sponsor makes the participant unsuitable for the study

• Previous treatment with an investigational agent for HBV other than ABI-H0731 in the last 6 months before screening

• History of hepatocellular carcinoma (HCC)

• Females who are lactating or pregnant or wish to become pregnant are excluded from the study

• Exclusionary laboratory parameters at screening:

• Platelet count <100,000/mm3

• Albumin <lower limit of normal (LLN)

• Direct bilirubin >1.2×upper limit of normal (ULN)

• Alanine aminotransferase (ALT) >10×ULN at screening

• Serum alpha fetoprotein (AFP) ≥100 ng/mL. If AFP at Screening is >ULN but <100 ng/mL, participant is eligible if a hepatic imaging study prior to the initiation of study drug reveals no lesions suspicious of possible HCC

• International Normalized Ratio (INR) >1.5×ULN

• Glomerular filtration rate (GFR) <60 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Southern California Research Center	Coronado	California	United States	92118
2	Asia Pacific Liver Center	Los Angeles	California	United States	90057
3	Research and Education	San Diego	California	United States	92105
4	Quest Clinical Research	San Francisco	California	United States	94115
5	Johns Hopkins University School of Medicine	Baltimore	Maryland	United States	21287
6	NYU Langone Health	New York	New York	United States	10016
7	Xiaoli Ma MD	Philadelphia	Pennsylvania	United States	19107
8	GI Research Institute	Vancouver	British Columbia	Canada	V6Z 2K5
9	Toronto Liver Center	Toronto	Ontario	Canada	M6H 3M1
10	University of Hong Kong, Queen Mary Hospital	Hong Kong		Hong Kong
11	Waikato Hospital	Hamilton		New Zealand
12	King's College London	London		United Kingdom

Sponsors and Collaborators

• Assembly Biosciences

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jun 18, 2018
• Statistical Analysis Plan - Aug 6, 2019

More Information

Publications

None provided.

• Responsible Party: Assembly Biosciences
• ClinicalTrials.gov Identifier: NCT03577171
• Other Study ID Numbers: ABI-H0731-202
• First Posted: Jul 5, 2018
• Last Update Posted: Jan 28, 2021
• Last Verified: Jan 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Assembly Biosciences: cHBV; HBV; HBeAg-positive; hepatitis B; vebicorvir; VBR
• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic; Entecavir

Study Results

Participant Flow

Arm/Group Title	ABI-H0731 + SOC ETV	Placebo + SOC ETV
Arm/Group Description	Participants with chronic hepatitis B infection (cHBV) who are currently not being treated will receive ABI-H0731 along with standard of care (SOC) entecavir (ETV) tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary. ABI-H0731: Participants will receive 300mg QD of ABI-H0731 tablets orally. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.	Participants with cHBV who are currently not being treated will receive matching placebo along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert. Placebo Oral Tablet: Participants will receive matching QD placebo tablets orally.
Period Title: Overall Study
STARTED	13	12
COMPLETED	13	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	ABI-H0731 + SOC ETV	Placebo + SOC ETV	Total
Arm/Group Description	Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary. ABI-H0731: Participants will receive 300mg QD of ABI-H0731 tablets orally. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.	Participants with cHBV who are currently not being treated will receive matching placebo along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert. Placebo Oral Tablet: Participants will receive matching QD placebo tablets orally.	Total of all reporting groups
Overall Participants	13	12	25
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.7 (14.13)	34.1 (11.39)	34.9 (12.65)
Sex: Female, Male (Count of Participants)
Female	10 76.9%	7 58.3%	17 68%
Male	3 23.1%	5 41.7%	8 32%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	13 100%	12 100%	25 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	13 100%	11 91.7%	24 96%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 8.3%	1 4%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
New Zealand	1 7.7%	0 0%	1 4%
Canada	1 7.7%	2 16.7%	3 12%
Hong Kong	3 23.1%	2 16.7%	5 20%
United States	7 53.8%	7 58.3%	14 56%
United Kingdom	1 7.7%	1 8.3%	2 8%

Outcome Measures

1. Primary Outcome

Title	Change in Mean log10 HBV DNA From Baseline (Day 1) to Week 12 or Week 24 on ABI H0731 + SOC ETV as Compared to Placebo + SOC ETV
Description	Hepatitis B virus (HBV) DNA was measured using COBAS TaqMan Version 2.0. The lower limit of quantitation (LLOQ) was 20 IU/mL and the limit of detection (LOD) was 10 IU/mL.
Time Frame	Baseline, Week 12, and Week 24

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: all randomized participants

Arm/Group Title	ABI-H0731 + SOC ETV	Placebo + SOC ETV
Arm/Group Description	Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary. ABI-H0731: Participants will receive 300mg QD of ABI-H0731 tablets orally. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.	Participants with cHBV who are currently not being treated will receive matching placebo along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert. Placebo Oral Tablet: Participants will receive matching QD placebo tablets orally.
Measure Participants	13	12
Baseline	7.91 (0.890)	8.03 (0.999)
Change from Baseline at Week 12	-4.45 (1.027)	-3.30 (1.182)
Change from Baseline at Week 24	-5.33 (1.594)	-4.20 (0.976)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABI-H0731 + SOC ETV, Placebo + SOC ETV
	Comments	Least Squares (LS) Mean Difference ABI-H0731 + SOC ETV minus Placebo + SOC ETV at Week 12
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0077
	Comments
	Method	Repeated measures analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.154
	Confidence Interval	(2-Sided) 95%; -1.986 to -0.322
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ABI-H0731 + SOC ETV, Placebo + SOC ETV
	Comments	Least Squares Mean Difference ABI-H0731 + SOC ETV minus Placebo + SOC ETV at Week 24
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0084
	Comments
	Method	Repeated measures analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.141
	Confidence Interval	(2-Sided) 95%; -1.973 to -0.309
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants One or More Adverse Events
Time Frame	Up to Follow-up (maximum up to Week 36)

Outcome Measure Data

Analysis Population Description

Safety population: all randomized participants who received any amount of study drug

Arm/Group Title	ABI-H0731 + SOC ETV	Placebo + SOC ETV
Arm/Group Description	Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary. ABI-H0731: Participants will receive 300mg QD of ABI-H0731 tablets orally. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.	Participants with cHBV who are currently not being treated will receive matching placebo along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert. Placebo Oral Tablet: Participants will receive matching QD placebo tablets orally.
Measure Participants	13	12
Count of Participants [Participants]	7 53.8%	5 41.7%

3. Secondary Outcome

Title	Number of Participants With Premature Study Discontinuation
Time Frame	Up to Follow-up (maximum up to Week 36)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	ABI-H0731 + SOC ETV	Placebo + SOC ETV
Arm/Group Description	Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary. ABI-H0731: Participants will receive 300mg QD of ABI-H0731 tablets orally. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.	Participants with cHBV who are currently not being treated will receive matching placebo along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert. Placebo Oral Tablet: Participants will receive matching QD placebo tablets orally.
Measure Participants	13	12
Count of Participants [Participants]	0 0%	0 0%

4. Secondary Outcome

Title	Number of Participants With One or More Abnormal Safety Laboratory Result
Time Frame	Up to Week 36

Outcome Measure Data

Analysis Population Description

Safety population: all randomized participants who received any amount of study drug

Arm/Group Title	ABI-H0731 + SOC ETV	Placebo + SOC ETV
Arm/Group Description	Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary. ABI-H0731: Participants will receive 300mg QD of ABI-H0731 tablets orally. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.	Participants with cHBV who are currently not being treated will receive matching placebo along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert. Placebo Oral Tablet: Participants will receive matching QD placebo tablets orally.
Measure Participants	13	12
Count of Participants [Participants]	8 61.5%	10 83.3%

5. Secondary Outcome

Title	Number of Participants With a Clinically-significant Electrocardiogram Abnormality
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

Safety population: all randomized participants who received any amount of study drug

Arm/Group Title	ABI-H0731 + SOC ETV	Placebo + SOC ETV
Arm/Group Description	Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary. ABI-H0731: Participants will receive 300mg QD of ABI-H0731 tablets orally. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.	Participants with cHBV who are currently not being treated will receive matching placebo along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert. Placebo Oral Tablet: Participants will receive matching QD placebo tablets orally.
Measure Participants	13	12
Count of Participants [Participants]	0 0%	0 0%

6. Secondary Outcome

Title	Number of Participants With a Clinically-significant Change in Vital Signs
Description	Vital signs assessed were body temperature, respiratory rate, and pulse rate
Time Frame	Baseline and up to Week 24

Outcome Measure Data

Analysis Population Description

Safety population: all randomized participants who received any amount of study drug

Arm/Group Title	ABI-H0731 + SOC ETV	Placebo + SOC ETV
Arm/Group Description	Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary. ABI-H0731: Participants will receive 300mg QD of ABI-H0731 tablets orally. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.	Participants with cHBV who are currently not being treated will receive matching placebo along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert. Placebo Oral Tablet: Participants will receive matching QD placebo tablets orally.
Measure Participants	13	12
Count of Participants [Participants]	0 0%	0 0%

7. Secondary Outcome

Title	Number of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Have Normal ALT at Week 24 on ABI-H0731 + SOC ETV as Compared to Placebo + SOC ETV
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Participants in the ITT population with abnormal ALT at Baseline

Arm/Group Title	ABI-H0731 + SOC ETV	Placebo + SOC ETV
Arm/Group Description	Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary. ABI-H0731: Participants will receive 300mg QD of ABI-H0731 tablets orally. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.	Participants with cHBV who are currently not being treated will receive matching placebo along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert. Placebo Oral Tablet: Participants will receive matching QD placebo tablets orally.
Measure Participants	4	4
Count of Participants [Participants]	4 30.8%	2 16.7%

8. Secondary Outcome

Title	Number of Participants With a Decline in Viral DNA to Below Limit of Quantitation on ABI-H0731 + SOC ETV as Compared to Placebo + SOC ETV
Description	HBV DNA was measured using COBAS TaqMan Version 2.0. The LLOQ was 20 IU/mL and the LOD was 10 IU/mL. The number of participants with HBV DNA below the limit of quantitation (<20 IU/mL) and target detected (≥10 IU/mL) was assessed.
Time Frame	Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

ITT population and had viral DNA data available

Arm/Group Title	ABI-H0731 + SOC ETV	Placebo + SOC ETV
Arm/Group Description	Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary. ABI-H0731: Participants will receive 300mg QD of ABI-H0731 tablets orally. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.	Participants with cHBV who are currently not being treated will receive matching placebo along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert. Placebo Oral Tablet: Participants will receive matching QD placebo tablets orally.
Measure Participants	13	12
Baseline	0 0%	0 0%
Week 2	0 0%	0 0%
Week 4	0 0%	0 0%
Week 8	1 7.7%	0 0%
Week 12	1 7.7%	0 0%
Week 16	2 15.4%	0 0%
Week 20	1 7.7%	1 8.3%
Week 24	3 23.1%	1 8.3%

9. Secondary Outcome

Title	Median Time to Viral Suppression, Defined as HBV DNA <20 IU/mL, on ABI-H0731 + ETV as Compared to Placebo + ETV
Description	Median time to viral suppression will be calculated and evaluated between participants on ABI-H0731 + ETV as compared to placebo + ETV.
Time Frame	Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

Median time to viral suppression could not be calculated because fewer than 50% of participants achieved viral suppression within 24 weeks.

Arm/Group Title	ABI-H0731 + SOC ETV	Placebo + SOC ETV
Arm/Group Description	Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary. ABI-H0731: Participants will receive 300mg QD of ABI-H0731 tablets orally. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.	Participants with cHBV who are currently not being treated will receive matching placebo along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert. Placebo Oral Tablet: Participants will receive matching QD placebo tablets orally.
Measure Participants	0	0

10. Secondary Outcome

Title	Number of Participants With Emergence of Resistant HBV Variants on ABI-H0731 + SOC ETV as Compared to Placebo + SOC ETV
Description	Emergence of a resistant HBV variant was defined as an increase of ≥1 log10 IU/mL from the nadir in HBV DNA.
Time Frame	Up to Week 36

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	ABI-H0731 + SOC ETV	Placebo + SOC ETV
Arm/Group Description	Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary. ABI-H0731: Participants will receive 300mg QD of ABI-H0731 tablets orally. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.	Participants with cHBV who are currently not being treated will receive matching placebo along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert. Placebo Oral Tablet: Participants will receive matching QD placebo tablets orally.
Measure Participants	13	12
Emergence of resistant HBV variants	1 7.7%	1 8.3%
No emergence of resistant HBV variants	12 92.3%	11 91.7%

11. Secondary Outcome

Title	Trough Levels of ABI-H0731 on ABI-H0731 + SOC ETV Therapy
Time Frame	Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24

Outcome Measure Data

Analysis Population Description

Results were analyzed and reported only for participants in the safety population who received ABI-H0731 + SOC ETV and had ABI-H0731 pharmacokinetic data assessments available.

Arm/Group Title	ABI-H0731 + SOC ETV
Arm/Group Description	Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary. ABI-H0731: Participants will receive 300mg QD of ABI-H0731 tablets orally. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.
Measure Participants	13
Baseline (Day 1)	NA (NA)
Week 2	1480 (458)
Week 4	1290 (434)
Week 12	1270 (413)
Week 24	1470 (547)

12. Secondary Outcome

Title	Trough Levels of ETV on ABI-H0731 + ETV Therapy as Compared With Placebo + ETV Therapy
Time Frame	Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24

Outcome Measure Data

Analysis Population Description

Results were analyzed and reported only for participants in the safety population who had ETV pharmacokinetic data assessments available.

Arm/Group Title	ABI-H0731 + SOC ETV	Placebo + SOC ETV
Arm/Group Description	Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary. ABI-H0731: Participants will receive 300mg QD of ABI-H0731 tablets orally. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.	Participants with cHBV who are currently not being treated will receive matching placebo along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert. Placebo Oral Tablet: Participants will receive matching QD placebo tablets orally.
Measure Participants	13	12
Baseline (Day 1)	0.00325 (0.0113)	0 (0)
Week 2	0.432 (0.126)	0.497 (0.473)
Week 4	0.419 (0.119)	0.618 (0.736)
Week 12	0.378 (0.149)	0.666 (0.766)
Week 24	0.411 (0.143)	0.408 (0.131)

13. Secondary Outcome

Title	Trough to Peak Ratios of ABI-H0731 on ABI-H0731 + ETV Therapy
Time Frame	Baseline, Weeks 2, 4, 12, and 24

Outcome Measure Data

Analysis Population Description

Trough to peak ratios were not calculated due to an insufficient number of optional peak exposure samples.

Arm/Group Title	ABI-H0731 + SOC ETV
Arm/Group Description	Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary. ABI-H0731: Participants will receive 300mg QD of ABI-H0731 tablets orally. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.
Measure Participants	0

14. Secondary Outcome

Title	Trough to Peak Ratios of ETV on ABI-H0731 + ETV Therapy as Compared With Placebo + ETV Therapy
Time Frame	Baseline, Weeks 2, 4, 12, 24, and 28

Outcome Measure Data

Analysis Population Description

Trough to peak ratios were not calculated due to an insufficient number of optional peak exposure samples.

Arm/Group Title	ABI-H0731 + SOC ETV	Placebo + SOC ETV
Arm/Group Description	Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary. ABI-H0731: Participants will receive 300mg QD of ABI-H0731 tablets orally. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.	Participants with cHBV who are currently not being treated will receive matching placebo along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert. Placebo Oral Tablet: Participants will receive matching QD placebo tablets orally.
Measure Participants	0	0

Adverse Events

Time Frame	Up to Week 36
Adverse Event Reporting Description	Safety population
Arm/Group Title	ABI-H0731 + SOC ETV		Placebo + SOC ETV
Arm/Group Description	Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary. ABI-H0731: Participants will receive 300mg QD of ABI-H0731 tablets orally. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.		Participants with cHBV who are currently not being treated will receive matching placebo along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary. SOC ETV: Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert. Placebo Oral Tablet: Participants will receive matching QD placebo tablets orally.
All Cause Mortality
	ABI-H0731 + SOC ETV		Placebo + SOC ETV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/12 (0%)
Serious Adverse Events
	ABI-H0731 + SOC ETV		Placebo + SOC ETV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	ABI-H0731 + SOC ETV		Placebo + SOC ETV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/13 (53.8%)		5/12 (41.7%)
Gastrointestinal disorders
Abdominal pain lower	0/13 (0%)	0	1/12 (8.3%)	1
Abdominal pain upper	1/13 (7.7%)	1	0/12 (0%)	0
Dyspepsia	1/13 (7.7%)	1	0/12 (0%)	0
General disorders
Pain	1/13 (7.7%)	1	0/12 (0%)	0
Infections and infestations
Upper respiratory tract infection	1/13 (7.7%)	1	1/12 (8.3%)	2
Folliculitis	1/13 (7.7%)	1	0/12 (0%)	0
Viral infection	0/13 (0%)	0	1/12 (8.3%)	1
Investigations
Alanine aminotransferase increased	1/13 (7.7%)	1	2/12 (16.7%)	2
Electrocardiogram T wave abnormal	0/13 (0%)	0	1/12 (8.3%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/13 (7.7%)	1	0/12 (0%)	0
Pain in extremity	0/13 (0%)	0	1/12 (8.3%)	1
Nervous system disorders
Dizziness	1/13 (7.7%)	1	1/12 (8.3%)	1
Headache	2/13 (15.4%)	2	0/12 (0%)	0
Psychiatric disorders
Stress	0/13 (0%)	0	1/12 (8.3%)	1
Reproductive system and breast disorders
Dysmenorrhoea	1/13 (7.7%)	1	0/12 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/13 (0%)	0	1/12 (8.3%)	1
Epistaxis	0/13 (0%)	0	1/12 (8.3%)	1
Skin and subcutaneous tissue disorders
Pruritus	2/13 (15.4%)	2	0/12 (0%)	0
Acne	1/13 (7.7%)	1	0/12 (0%)	0
Skin irritation	0/13 (0%)	0	1/12 (8.3%)	1

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Assembly Biosciences agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Assembly Biosciences supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.