Trial Outcomes & Findings for Ledipasvir/Sofosbuvir for Hepatitis B Virus Infection (NCT NCT03312023)
NCT ID: NCT03312023
Last Updated: 2021-09-20
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
21 participants
Primary outcome timeframe
12 weeks
Results posted on
2021-09-20
Participant Flow
Participant milestones
| Measure |
Group A (LDV/SOF for Low Replicative HBV)
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
|
Group B (LDV/SOF for Viral Suppressed HBV)
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
|
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.
Sofosbuvir 400 MG \[Sovaldi\]: 1 pill once daily for 12 weeks for Group C
|
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.
Ledipasvir 90 MG: 1 pill once daily for 12 weeks for Group D
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
8
|
5
|
4
|
4
|
|
Overall Study
Completed Week 12
|
8
|
5
|
4
|
4
|
|
Overall Study
COMPLETED
|
8
|
5
|
4
|
4
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Ledipasvir/Sofosbuvir for Hepatitis B Virus Infection
Baseline characteristics by cohort
| Measure |
Group A (LDV/SOF for Low Replicative HBV)
n=8 Participants
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
|
Group B (LDV/SOF for Viral Suppressed HBV)
n=5 Participants
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
|
Group C (SOF for Low Replicative HBV)
n=4 Participants
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
|
Group D (LDV for Low Replicative HBV)
n=4 Participants
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
n=21 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
47.3 years
n=5 Participants
|
57.6 years
n=7 Participants
|
43.5 years
n=5 Participants
|
52.3 years
n=4 Participants
|
50.0 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
16 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
21 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
8 participants
n=5 Participants
|
5 participants
n=7 Participants
|
4 participants
n=5 Participants
|
4 participants
n=4 Participants
|
21 participants
n=21 Participants
|
|
Negative eAg
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
21 Participants
n=21 Participants
|
|
Normal ALT
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
20 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: Intention to treat population - all subjects who have received at least one study drug.
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.
Outcome measures
| Measure |
Group A (LDV/SOF for Low Replicative HBV)
n=8 Participants
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
|
Group B (LDV/SOF for Viral Suppressed HBV)
n=5 Participants
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
|
Group C (SOF for Low Replicative HBV)
n=4 Participants
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
|
Group D (LDV for Low Replicative HBV)
n=4 Participants
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
|
|---|---|---|---|---|
|
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.
|
0.39 Log10 IU/mL
Standard Deviation 0.2
|
0.40 Log10 IU/mL
Standard Deviation 0.3
|
0.19 Log10 IU/mL
Standard Deviation 0.3
|
-0.05 Log10 IU/mL
Standard Deviation 0.1
|
PRIMARY outcome
Timeframe: 12 WeeksNumber of subjects who discontinued study drug due to adverse event
Outcome measures
| Measure |
Group A (LDV/SOF for Low Replicative HBV)
n=8 Participants
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
|
Group B (LDV/SOF for Viral Suppressed HBV)
n=5 Participants
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
|
Group C (SOF for Low Replicative HBV)
n=4 Participants
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
|
Group D (LDV for Low Replicative HBV)
n=4 Participants
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
|
|---|---|---|---|---|
|
Incidence of Adverse Events Leading to Permanent Discontinuation of Ledipasvir and/or Sofosbuvir Treatment in Subjects With Chronic Hepatitis B Infection.
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 12 weeksSubjects 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.
Outcome measures
| Measure |
Group A (LDV/SOF for Low Replicative HBV)
n=8 Participants
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
|
Group B (LDV/SOF for Viral Suppressed HBV)
n=5 Participants
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
|
Group C (SOF for Low Replicative HBV)
n=4 Participants
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
|
Group D (LDV for Low Replicative HBV)
n=4 Participants
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
|
|---|---|---|---|---|
|
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.
|
0.51 Log10 IU/mL
Standard Deviation 0.6
|
0 Log10 IU/mL
Standard Deviation 0
|
0.68 Log10 IU/mL
Standard Deviation 0.4
|
0.21 Log10 IU/mL
Standard Deviation 0.8
|
Adverse Events
Group A (LDV/SOF for Low Replicative HBV)
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Group B (LDV/SOF for Viral Suppressed HBV)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Group C (SOF for Low Replicative HBV)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Group D (LDV for Low Replicative HBV)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Group A (LDV/SOF for Low Replicative HBV)
n=8 participants at risk
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
|
Group B (LDV/SOF for Viral Suppressed HBV)
n=5 participants at risk
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
|
Group C (SOF for Low Replicative HBV)
n=4 participants at risk
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
|
Group D (LDV for Low Replicative HBV)
n=4 participants at risk
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
|
|---|---|---|---|---|
|
Nervous system disorders
Headache
|
50.0%
4/8 • Number of events 10 • 24 weeks
|
40.0%
2/5 • Number of events 3 • 24 weeks
|
25.0%
1/4 • Number of events 1 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection
|
25.0%
2/8 • Number of events 3 • 24 weeks
|
20.0%
1/5 • Number of events 3 • 24 weeks
|
25.0%
1/4 • Number of events 1 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Blood and lymphatic system disorders
Anemia
|
12.5%
1/8 • Number of events 2 • 24 weeks
|
0.00%
0/5 • 24 weeks
|
25.0%
1/4 • Number of events 3 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
12.5%
1/8 • Number of events 1 • 24 weeks
|
0.00%
0/5 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
12.5%
1/8 • Number of events 1 • 24 weeks
|
0.00%
0/5 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
General disorders
Fatigue
|
12.5%
1/8 • Number of events 5 • 24 weeks
|
0.00%
0/5 • 24 weeks
|
25.0%
1/4 • Number of events 1 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Gastrointestinal disorders
Hemorrhoids
|
12.5%
1/8 • Number of events 1 • 24 weeks
|
0.00%
0/5 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
12.5%
1/8 • Number of events 1 • 24 weeks
|
0.00%
0/5 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • Number of events 1 • 24 weeks
|
|
Renal and urinary disorders
Nephrolithiasis
|
12.5%
1/8 • Number of events 1 • 24 weeks
|
0.00%
0/5 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
12.5%
1/8 • Number of events 1 • 24 weeks
|
0.00%
0/5 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Skin and subcutaneous tissue disorders
Rash, maculopapular
|
12.5%
1/8 • Number of events 1 • 24 weeks
|
0.00%
0/5 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis, allergic
|
12.5%
1/8 • Number of events 1 • 24 weeks
|
0.00%
0/5 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Skin and subcutaneous tissue disorders
Skin laceration
|
12.5%
1/8 • Number of events 1 • 24 weeks
|
0.00%
0/5 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Synovial cyst
|
12.5%
1/8 • Number of events 1 • 24 weeks
|
0.00%
0/5 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Infections and infestations
Tooth infection
|
12.5%
1/8 • Number of events 1 • 24 weeks
|
0.00%
0/5 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
General disorders
Edema, peripheral
|
0.00%
0/8 • 24 weeks
|
20.0%
1/5 • Number of events 1 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/8 • 24 weeks
|
20.0%
1/5 • Number of events 1 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/8 • 24 weeks
|
0.00%
0/5 • 24 weeks
|
25.0%
1/4 • Number of events 1 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/8 • 24 weeks
|
0.00%
0/5 • 24 weeks
|
25.0%
1/4 • Number of events 1 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/8 • 24 weeks
|
0.00%
0/5 • 24 weeks
|
25.0%
1/4 • Number of events 1 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscle strain
|
0.00%
0/8 • 24 weeks
|
0.00%
0/5 • 24 weeks
|
25.0%
1/4 • Number of events 1 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/8 • 24 weeks
|
0.00%
0/5 • 24 weeks
|
25.0%
1/4 • Number of events 1 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/8 • 24 weeks
|
0.00%
0/5 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • Number of events 2 • 24 weeks
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/8 • 24 weeks
|
0.00%
0/5 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • Number of events 2 • 24 weeks
|
|
Infections and infestations
Tooth abscess
|
0.00%
0/8 • 24 weeks
|
0.00%
0/5 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • Number of events 1 • 24 weeks
|
Additional Information
Dr. Joel V. Chua
Institute of Human Virology, University of Maryland Baltimore
Phone: 1-410-706-5704
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place