APOSTLE: Ledipasvir/Sofosbuvir for Hepatitis B Virus Infection

• Sponsor: University of Maryland, Baltimore (Other)
• Overall Status: Completed
• CT.gov ID: NCT03312023
• Collaborator: Gilead Sciences (Industry)
• Enrollment: 21
• Location: 1
• Arms: 4
• Actual Duration (Months): 40.9
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The goals of therapy against chronic hepatitis B are to decrease the morbidity and mortality related to chronic HBV infection. Currently available antiviral therapy can suppress viral replication but only a small proportion attain functional cure, which is defined as HBV surface antigen-to-antibody seroconversion. Hepatitis B surface antigen (HBsAg) is a marker of persistent hepatitis B infection.

It has been observed that patients who had both hepatitis B and hepatitis C, and who were treated for their hepatitis C with 12 weeks of ledipasvir/sofosbuvir for had a decline in HBsAg levels. This study hypothesizes that a similar decrease would be seen in mono-infected hepatitis B subjects over the course of 12 weeks treatment with ledipasvir/sofosbuvir.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B	Drug: Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]; Drug: Sofosbuvir 400 MG [Sovaldi]; Drug: Ledipasvir 90 MG	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Open-label Study, multi-armOpen-label Study, multi-arm
• Masking: None (Open Label)
• Masking Description: Ten potential subjects for Groups C and D will be randomized in a 1:1 fashion.
• Primary Purpose: Treatment
• Official Title: A Phase II Open-Label Study of Ledipasvir/Sofosbuvir for 12 Weeks in Subjects With Hepatitis B Virus Infection
• Actual Study Start Date: Feb 1, 2018
• Actual Primary Completion Date: Aug 10, 2020
• Actual Study Completion Date: Jun 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A (LDV/SOF for low replicative HBV) 12 week treatment with ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis B in low replicative state.	Drug: Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]; 1 pill once daily for 12 weeks for Group A; Other Names: Harvoni
Experimental: Group B (LDV/SOF for viral suppressed HBV) 12 week treatment with ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis B, virally suppressed.	Drug: Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]; 1 pill once daily for 12 weeks for Group A; Other Names: Harvoni
Experimental: Group C (SOF for low replicative HBV) 12 weeks treatment with sofosbuvir (Sovaldi) for chronic hepatitis B in low replicative state. Randomized 1:1 with Group D.	Drug: Sofosbuvir 400 MG [Sovaldi]; 1 pill once daily for 12 weeks for Group C; Other Names: GS-7977
Experimental: Group D (LDV for low replicative HBV) 12 weeks treatment with ledipasvir for chronic hepatitis B in low replicative state. Randomized 1:1 with Group C.	Drug: Ledipasvir 90 MG; 1 pill once daily for 12 weeks for Group D; Other Names: GS-5885

Outcome Measures

Primary Outcome Measures

1. Change of Serum Hepatitis B Surface Antigen (HBsAg as Measured in log10 IU/mL) Level as an Indicator of Antiviral Activity of Ledipasvir and/or Sofosbuvir in Subjects With Chronic Hepatitis B From Baseline to End of 12 Weeks Treatment. [12 weeks]

   Subjects with chronic hepatitis B will be give 12 weeks of ledipasvir and/or sofosbuvir and their HBsAg will be measured at baseline, on each visits during therapy, and at end of therapy (week 12). The change (decline) in HBsAg from baseline to end of the 12 week treatment will be compared.

2. Incidence of Adverse Events Leading to Permanent Discontinuation of Ledipasvir and/or Sofosbuvir Treatment in Subjects With Chronic Hepatitis B Infection. [12 Weeks]

   Number of subjects who discontinued study drug due to adverse event

Secondary Outcome Measures

1. Changes in Serum Hepatitis B Virus DNA Levels (HBV DNA as Measured in IU/mL) With Treatment of Ledipasvir and/or Sofosbuvir From Baseline to End of 12 Weeks of Treatment in Subjects With Chronic Hepatitis B Infection. [12 weeks]

   Subjects with chronic hepatitis B will be give 12 weeks of ledipasvir and/or sofosbuvir and their serum hepatitis B DNA levels (HBV DNA) will be measured at baseline, on each visits during therapy, and at end of therapy (week 12). The change in HBV DNA levels from baseline to end of the 12 week treatment will be compared. Note: Group B (virally suppressed HBV subjects) - all had HBV DNA below the limit of detection; Hence, mean change was 0.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

INCLUSION CRITERIA

Participants in Groups A, C & D (Chronic HBV, low replicative state not requiring treatment):

1. Provision of signed and dated informed consent form

2. Stated willingness to comply with all study procedures and availability for the duration of the study

3. Male or female, aged 18 or older at screening

4. Diagnosed with chronic hepatitis B infection defined as one of the following:

5. HBsAg or HBV DNA positivity for at least 6 months

6. Medical records indicating a chronic HBV infection

7. HBeAg negative at screening

8. HBV DNA > lower level of quantitation (LLOQ)

9. Quantitative HBsAg at least 10 IU/mL at screening

10. Ability to take oral medication and be willing to adhere to the twelve week study drug regimen

11. For females of reproductive potential: usual practice of complete abstinence from sexual intercourse with a member of the opposite sex OR use of at least one form of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 30 days after the end of study drug administration

12. For males of reproductive potential: usual practice of complete abstinence from sexual intercourse with a member of the opposite sex OR use of at least one form of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 14 days after the end of study drug administration

13. Ability to communicate effectively with the study investigator and key staff

14. Medical management provided by a primary care provider

15. Ability to store medications at a room temperature of less than 86 degrees Fahrenheit

16. Not on antiviral therapy or requiring treatment for HBV during screening

Participants in Group B (Chronic HBV, virally suppressed):

1. Provision of signed and dated informed consent form

2. Stated willingness to comply with all study procedures and availability for the duration of the study

3. Male or female, aged 18 or older at screening

4. Diagnosed with chronic hepatitis B infection defined as one of the following:

5. HBsAg or HBV DNA positivity for at least 6 months

6. Medical records indicating a chronic HBV infection

7. Receiving oral anti-HBV medications (either tenofovir alafenamide, tenofovir disoproxil fumarate, entecavir, or a combination of no more than 2 of these agents) for at least three months prior to enrollment

8. HBV DNA ˂ lower level of quantitation (LLOQ) at screening and for at least three months prior

9. Quantitative HBsAg at least 10 IU/mL at screening

10. Ability to take oral medication and be willing to adhere to the twelve week study drug regimen

11. For females of reproductive potential: usual practice of complete abstinence from sexual intercourse with a member of the opposite sex OR use of at least one form of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 30 days after the end of study drug administration

12. For males of reproductive potential: usual practice of complete abstinence from sexual intercourse with a member of the opposite sex OR use of at least one form of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 14 days after the end of study drug administration

13. Ability to communicate effectively with the study investigator and key staff

14. Medical management provided by a primary care provider

15. Ability to store medications at a room temperature of less than 86 degrees Fahrenheit

EXCLUSION CRITERIA

1. Coinfection with hepatitis C, hepatitis D or human immunodeficiency virus (HIV)

2. Pregnancy or lactation

3. Known allergic reactions to sofosbuvir or ledipasvir

4. Treatment with another investigational drug or other intervention within three months

5. Evidence of cirrhosis or hepatic decompensation such as:

• Platelets less than 100,000 /mm3

• Albumin less than 3.5 g/dL

• INR greater than 1.7 or Prothrombin time of 1.5 times the upper limit of normal (ULN)

• Total bilirubin of 1.5 times the upper limit of normal

• FibroTest (or FibroSure®) of 0.75 or greater

1. Abnormal hematological and biochemical parameters at screening including:

• White blood cell count less than 2500 cells/uL

• Absolute neutrophil count (ANC) less than 1,000 cells/mm3 (less than 750 mm3 for African or African-American subjects)

• Hemoglobin less than 12 g/dL for males, less than 11 g/dL for females

• AST or ALT of two times the upper limit of normal

• Estimated GFR less than 50 mL/min

• Glycosylated hemoglobin (HbA1c) greater than 8.5%

1. Current or prior history of any of the following:

• Immunodeficiency disorders or autoimmune disease (e.g. Systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel diseases, sarcoidosis, psoriasis of greater than mild severity)

• Severe pulmonary disorders, significant cardiac diseases

• Gastrointestinal disorder with post-operative condition that could interfere with the absorption of the study drugs

• Significant psychiatric illness that in the judgment of the Investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent

• Any malignancy diagnosed within 5 years (not including recent localized treatment of squamous or non-invasive basal cell skin cancer; cervical carcinoma in situ appropriately treated prior to screening)

• Solid organ transplantation

• Poor venous access

1. Screening ECG with clinically significant findings

2. Evidence of HCC (e.g., α fetoprotein > 50ng/mL or radiologic evidence)

3. Clinically significant illicit drug or alcohol abuse within 12 months of screening. Subjects on methadone maintenance treatment or prescribed opioid may be included.

4. Use of amiodarone within 90 days of enrollment; or carbamazepine, phenytoin, phenobarbital, oxcarbazepine, rifabutin, rifampin, rifapentine, St. John's wort, rosuvastatin, or interferon within 30 days of enrollment or expected use of these prohibited drugs during study participation. Use of or expected need of proton-pump inhibitors more than 20 mg omeprazole equivalent or H2 receptor antagonist more than 40 mg famotidine BID equivalent within 7 days of enrollment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institute of Human Virology (IHV), University of Maryland Baltimore	Baltimore	Maryland	United States	21201

Sponsors and Collaborators

• University of Maryland, Baltimore
• Gilead Sciences

Investigators

• Principal Investigator: Joel V Chua, MD, University of Maryland, College Park

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 18, 2019

More Information

Publications

None provided.

• Responsible Party: Joel Chua, Assistant Professor, University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT03312023
• Other Study ID Numbers: HP-00074723
• First Posted: Oct 17, 2017
• Last Update Posted: Sep 20, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Joel Chua, Assistant Professor, University of Maryland, Baltimore: Hepatitis B; HBsAg; Ledipasvir/Sofosbuvir; Hepatitis B treatment
• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Virus Diseases; Herpesviridae Infections; Hepatitis; Sofosbuvir; Ledipasvir, sofosbuvir drug combination; Ledipasvir

Study Results

Participant Flow

Arm/Group Title	Group A (LDV/SOF for Low Replicative HBV)	Group B (LDV/SOF for Viral Suppressed HBV)	Group C (SOF for Low Replicative HBV)	Group D (LDV for Low Replicative HBV)
Arm/Group Description	12 week treatment with ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis B in low replicative state. Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]: 1 pill once daily for 12 weeks for Group A	12 week treatment with ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis B, virally suppressed. Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]: 1 pill once daily for 12 weeks for Group A	12 weeks treatment with sofosbuvir (Sovaldi) for chronic hepatitis B in low replicative state. Randomized 1:1 with Group D. Sofosbuvir 400 MG [Sovaldi]: 1 pill once daily for 12 weeks for Group C	12 weeks treatment with ledipasvir for chronic hepatitis B in low replicative state. Randomized 1:1 with Group C. Ledipasvir 90 MG: 1 pill once daily for 12 weeks for Group D
Period Title: Overall Study
STARTED	8	5	4	4
Completed Week 12	8	5	4	4
COMPLETED	8	5	4	4
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Group A (LDV/SOF for Low Replicative HBV)	Group B (LDV/SOF for Viral Suppressed HBV)	Group C (SOF for Low Replicative HBV)	Group D (LDV for Low Replicative HBV)	Total
Arm/Group Description	12 week treatment with ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis B in low replicative state. Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]: 1 pill once daily for 12 weeks for Group A	12 week treatment with ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis B, virally suppressed. Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]: 1 pill once daily for 12 weeks for Group A	12 weeks treatment with sofosbuvir (Sovaldi) for chronic hepatitis B in low replicative state. Randomized 1:1 with Group D. Sofosbuvir 400 MG [Sovaldi]: 1 pill once daily for 12 weeks for Group C	12 weeks treatment with ledipasvir for chronic hepatitis B in low replicative state. Randomized 1:1 with Group C. Ledipasvir 90 MG: 1 pill once daily for 12 weeks for Group D	Total of all reporting groups
Overall Participants	8	5	4	4	21
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	47.3	57.6	43.5	52.3	50.0
Sex: Female, Male (Count of Participants)
Female	1 12.5%	2 40%	2 50%	0 0%	5 23.8%
Male	7 87.5%	3 60%	2 50%	4 100%	16 76.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	8 100%	5 100%	4 100%	4 100%	21 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	3 37.5%	3 60%	0 0%	0 0%	6 28.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	4 50%	2 40%	3 75%	3 75%	12 57.1%
White	1 12.5%	0 0%	1 25%	1 25%	3 14.3%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	8 100%	5 100%	4 100%	4 100%	21 100%
Negative eAg (Count of Participants)
Count of Participants [Participants]	8 100%	5 100%	4 100%	4 100%	21 100%
Normal ALT (Count of Participants)
Count of Participants [Participants]	8 100%	5 100%	3 75%	4 100%	20 95.2%

Outcome Measures

1. Primary Outcome

Title	Change of Serum Hepatitis B Surface Antigen (HBsAg as Measured in log10 IU/mL) Level as an Indicator of Antiviral Activity of Ledipasvir and/or Sofosbuvir in Subjects With Chronic Hepatitis B From Baseline to End of 12 Weeks Treatment.
Description	Subjects with chronic hepatitis B will be give 12 weeks of ledipasvir and/or sofosbuvir and their HBsAg will be measured at baseline, on each visits during therapy, and at end of therapy (week 12). The change (decline) in HBsAg from baseline to end of the 12 week treatment will be compared.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat population - all subjects who have received at least one study drug.

Arm/Group Title	Group A (LDV/SOF for Low Replicative HBV)	Group B (LDV/SOF for Viral Suppressed HBV)	Group C (SOF for Low Replicative HBV)	Group D (LDV for Low Replicative HBV)
Arm/Group Description	12 week treatment with ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis B in low replicative state. Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]: 1 pill once daily for 12 weeks for Group A	12 week treatment with ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis B, virally suppressed. Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]: 1 pill once daily for 12 weeks for Group A	12 weeks treatment with sofosbuvir (Sovaldi) for chronic hepatitis B in low replicative state. Randomized 1:1 with Group D. Sofosbuvir 400 MG [Sovaldi]: 1 pill once daily for 12 weeks for Group C	12 weeks treatment with ledipasvir for chronic hepatitis B in low replicative state. Randomized 1:1 with Group C. Ledipasvir 90 MG: 1 pill once daily for 12 weeks for Group D
Measure Participants	8	5	4	4
Mean (Standard Deviation) [Log10 IU/mL]	0.39 (0.2)	0.40 (0.3)	0.19 (0.3)	-0.05 (0.1)

2. Primary Outcome

Title	Incidence of Adverse Events Leading to Permanent Discontinuation of Ledipasvir and/or Sofosbuvir Treatment in Subjects With Chronic Hepatitis B Infection.
Description	Number of subjects who discontinued study drug due to adverse event
Time Frame	12 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A (LDV/SOF for Low Replicative HBV)	Group B (LDV/SOF for Viral Suppressed HBV)	Group C (SOF for Low Replicative HBV)	Group D (LDV for Low Replicative HBV)
Arm/Group Description	12 week treatment with ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis B in low replicative state. Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]: 1 pill once daily for 12 weeks for Group A	12 week treatment with ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis B, virally suppressed. Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]: 1 pill once daily for 12 weeks for Group A	12 weeks treatment with sofosbuvir (Sovaldi) for chronic hepatitis B in low replicative state. Randomized 1:1 with Group D. Sofosbuvir 400 MG [Sovaldi]: 1 pill once daily for 12 weeks for Group C	12 weeks treatment with ledipasvir for chronic hepatitis B in low replicative state. Randomized 1:1 with Group C. Ledipasvir 90 MG: 1 pill once daily for 12 weeks for Group D
Measure Participants	8	5	4	4
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

3. Secondary Outcome

Title	Changes in Serum Hepatitis B Virus DNA Levels (HBV DNA as Measured in IU/mL) With Treatment of Ledipasvir and/or Sofosbuvir From Baseline to End of 12 Weeks of Treatment in Subjects With Chronic Hepatitis B Infection.
Description	Subjects with chronic hepatitis B will be give 12 weeks of ledipasvir and/or sofosbuvir and their serum hepatitis B DNA levels (HBV DNA) will be measured at baseline, on each visits during therapy, and at end of therapy (week 12). The change in HBV DNA levels from baseline to end of the 12 week treatment will be compared. Note: Group B (virally suppressed HBV subjects) - all had HBV DNA below the limit of detection; Hence, mean change was 0.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A (LDV/SOF for Low Replicative HBV)	Group B (LDV/SOF for Virally Suppressed HBV)	Group C (SOF for Low Replicative HBV)	Group D (LDV for Low Replicative HBV)
Arm/Group Description	12 week treatment with ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis B in low replicative state. Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]: 1 pill once daily for 12 weeks for Group A	12 weeks of treatment with ledipasvir/sofosbuvir (Harvoni) for chronical hepatitis B virally suppressed on HBV meds	12 weeks treatment with sofosbuvir (Sovaldi) for chronic hepatitis B in low replicative state. Randomized 1:1 with Group D. Sofosbuvir 400 MG [Sovaldi]: 1 pill once daily for 12 weeks for Group C	12 weeks treatment with ledipasvir for chronic hepatitis B in low replicative state. Randomized 1:1 with Group C. Ledipasvir 90 MG: 1 pill once daily for 12 weeks for Group D
Measure Participants	8	5	4	4
Mean (Standard Deviation) [Log10 IU/mL]	0.51 (0.6)	0 (0)	0.68 (0.4)	0.21 (0.8)

Adverse Events

Time Frame	24 weeks
Arm/Group Title	Group A (LDV/SOF for Low Replicative HBV)		Group B (LDV/SOF for Viral Suppressed HBV)		Group C (SOF for Low Replicative HBV)		Group D (LDV for Low Replicative HBV)
Arm/Group Description	12 week treatment with ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis B in low replicative state. Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]: 1 pill once daily for 12 weeks for Group A		12 week treatment with ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis B, virally suppressed. Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]: 1 pill once daily for 12 weeks for Group A		12 weeks treatment with sofosbuvir (Sovaldi) for chronic hepatitis B in low replicative state. Randomized 1:1 with Group D. Sofosbuvir 400 MG [Sovaldi]: 1 pill once daily for 12 weeks for Group C		12 weeks treatment with ledipasvir for chronic hepatitis B in low replicative state. Randomized 1:1 with Group C. Ledipasvir 90 MG: 1 pill once daily for 12 weeks for Group D
All Cause Mortality
	Group A (LDV/SOF for Low Replicative HBV)		Group B (LDV/SOF for Viral Suppressed HBV)		Group C (SOF for Low Replicative HBV)		Group D (LDV for Low Replicative HBV)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Serious Adverse Events
	Group A (LDV/SOF for Low Replicative HBV)		Group B (LDV/SOF for Viral Suppressed HBV)		Group C (SOF for Low Replicative HBV)		Group D (LDV for Low Replicative HBV)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Group A (LDV/SOF for Low Replicative HBV)		Group B (LDV/SOF for Viral Suppressed HBV)		Group C (SOF for Low Replicative HBV)		Group D (LDV for Low Replicative HBV)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/8 (87.5%)		2/5 (40%)		4/4 (100%)		1/4 (25%)
Blood and lymphatic system disorders
Anemia	1/8 (12.5%)	2	0/5 (0%)	0	1/4 (25%)	3	0/4 (0%)	0
Gastrointestinal disorders
Hemorrhoids	1/8 (12.5%)	1	0/5 (0%)	0	0/4 (0%)	0	0/4 (0%)	0
Dyspepsia	0/8 (0%)	0	0/5 (0%)	0	1/4 (25%)	1	0/4 (0%)	0
Nausea	0/8 (0%)	0	0/5 (0%)	0	1/4 (25%)	1	0/4 (0%)	0
General disorders
Fatigue	1/8 (12.5%)	5	0/5 (0%)	0	1/4 (25%)	1	0/4 (0%)	0
Edema, peripheral	0/8 (0%)	0	1/5 (20%)	1	0/4 (0%)	0	0/4 (0%)	0
Infections and infestations
Tooth infection	1/8 (12.5%)	1	0/5 (0%)	0	0/4 (0%)	0	0/4 (0%)	0
Tooth abscess	0/8 (0%)	0	0/5 (0%)	0	0/4 (0%)	0	1/4 (25%)	1
Injury, poisoning and procedural complications
Fall	0/8 (0%)	0	0/5 (0%)	0	0/4 (0%)	0	1/4 (25%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	1/8 (12.5%)	1	0/5 (0%)	0	0/4 (0%)	0	0/4 (0%)	0
Back pain	1/8 (12.5%)	1	0/5 (0%)	0	0/4 (0%)	0	0/4 (0%)	0
Synovial cyst	1/8 (12.5%)	1	0/5 (0%)	0	0/4 (0%)	0	0/4 (0%)	0
Myalgia	0/8 (0%)	0	1/5 (20%)	1	0/4 (0%)	0	0/4 (0%)	0
Muscle strain	0/8 (0%)	0	0/5 (0%)	0	1/4 (25%)	1	0/4 (0%)	0
Nervous system disorders
Headache	4/8 (50%)	10	2/5 (40%)	3	1/4 (25%)	1	0/4 (0%)	0
Renal and urinary disorders
Nephrolithiasis	1/8 (12.5%)	1	0/5 (0%)	0	0/4 (0%)	0	0/4 (0%)	0
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection	2/8 (25%)	3	1/5 (20%)	3	1/4 (25%)	1	0/4 (0%)	0
Nasal congestion	1/8 (12.5%)	1	0/5 (0%)	0	0/4 (0%)	0	1/4 (25%)	1
Oropharyngeal pain	1/8 (12.5%)	1	0/5 (0%)	0	0/4 (0%)	0	0/4 (0%)	0
Rhinitis, allergic	1/8 (12.5%)	1	0/5 (0%)	0	0/4 (0%)	0	0/4 (0%)	0
Cough	0/8 (0%)	0	0/5 (0%)	0	1/4 (25%)	1	0/4 (0%)	0
Epistaxis	0/8 (0%)	0	0/5 (0%)	0	0/4 (0%)	0	1/4 (25%)	2
Skin and subcutaneous tissue disorders
Rash, maculopapular	1/8 (12.5%)	1	0/5 (0%)	0	0/4 (0%)	0	0/4 (0%)	0
Skin laceration	1/8 (12.5%)	1	0/5 (0%)	0	0/4 (0%)	0	0/4 (0%)	0
Dry skin	0/8 (0%)	0	0/5 (0%)	0	1/4 (25%)	1	0/4 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.