Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination in Adults With Chronic HCV and HBV Coinfection
Study Details
Study Description
Brief Summary
The primary objectives of this study are to determine the antiviral efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) in adults with chronic genotype 1 or 2 HCV infection who are coinfected with HBV in Taiwan.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: LDV/SOF LDV/SOF FDC for 12 weeks |
Drug: LDV/SOF
90/400 mg FDC tablet administered orally once daily
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) [Posttreatment Week 12]
SVR12 was defined as HCV RNA < the lower limit of quantification (LLOQ; 15 IU/mL) at 12 weeks after stopping study treatment.
- Percentage of Participants With Any Adverse Event Leading to Permanent Discontinuation of Study Drug [First dose date up to 12 weeks]
Secondary Outcome Measures
- Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) [Posttreatment Week 4]
SVR4 was defined as HCV RNA < LLOQ (15 IU/mL) at 4 weeks after stopping study treatment.
- Percentage of Participants With HCV RNA < LLOQ While on Treatment [Weeks 1, 2, 4, 8, and 12]
LLOQ = 15 IU/mL
- Percentage of Participants With HCV RNA < LLOQ at Posttreatment Weeks 24, 36, 48, 60, 72, 84, 96, and 108 [Posttreatment Weeks 24, 36, 48, 60, 72, 84, 96, and 108]
LLOQ = 15 IU/mL
- HCV RNA Change From Baseline While on Treatment [Weeks 1, 2, 4, 8, and 12]
- Percentage of Participants With Virologic Failure [First dose date up to Posttreatment Week 12]
Virologic failure was defined as : Breakthrough (confirmed HCV RNA ≥ LLOQ [15 IU/mL] after having previously had HCV RNA < LLOQ while on treatment), or Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment), or Relapse (HCV RNA ≥ LLOQ during the post-treatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available post-treatment measurement)
- Plasma HBV DNA Change From Baseline While on Treatment [Weeks 1, 2, 4, 8, and 12]
- Plasma HBV DNA Change From Baseline at Posttreatment Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, and 108 [Posttreatment Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, and 108]
- HBsAg Level Change From Baseline While on Treatment [Weeks 1, 2, 4, 8, and 12]
- HBsAg Level Change From Baseline at Posttreatment Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, and 108 [Posttreatment Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, and 108]
- Serum LOXL-2 Level Change From Baseline While on Treatment [Weeks 1, 2, 4, 8, and 12]
- Serum LOXL-2 Level Change From Baseline at Posttreatment Weeks 4, 12, and 36 [Posttreatment Weeks 4, 12, and 36]
- Percentage of Participants That Required HBV Therapy During the Study [First dose date up to Posttreatment Week 108]
- Fibrosis Status as Assessed by Fibroscan Score at Posttreatment Weeks 12, 60, and 108 [Posttreatment Weeks 12, 60, and 108]
FibroScan is a non-invasive device that assesses the hardness (or stiffness) of the liver using the technique of transient elastography. FibroScan results range from 2.5 kPa to 75 kPa with higher scores indicating greater liver stiffness. Per protocol, cirrhosis status was determined as follows: Presence of cirrhosis = FibroScan result of > 12.5 kPa Absence of cirrhosis = FibroScan result of ≤ 12.5 kPa
- Percentage of Participants That Develop Hepatocellular Carcinoma (HCC) During the Study [First dose date up to Posttreatment Week 108]
Eligibility Criteria
Criteria
Key Inclusion Criteria:
-
Individuals ≥ 40 kg in weight with chronic genotype 1 or 2 HCV and HBV coinfection
-
Individuals must not be taking or requiring treatment with HBV antiviral therapy at screening. For participants that are HBV treatment experienced, the most recent treatment must have been completed at least 6 months prior to Day 1.
-
Cirrhosis determination by Fibroscan
-
Screening laboratory values within defined thresholds
-
Use of two effective contraception methods if female or male is of childbearing potential
Key Exclusion Criteria:
-
Current or prior history of clinically-significant illness or any other major medical disorder that may interfere with individual's treatment, assessment or compliance with the protocol
-
Pregnant or nursing female
-
Infection with human immunodeficiency virus (HIV) or hepatitis delta virus (HDV)
-
Hepatocellular carcinoma (HCC) or other malignancy
-
Current or prior history of clinical hepatic decompensation
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Changhua | Taiwan | |||
2 | Chiayi City | Taiwan | |||
3 | Kaohsiung City | Taiwan | |||
4 | Kaohsiung | Taiwan | |||
5 | Keelung | Taiwan | |||
6 | Taichung | Taiwan | |||
7 | Tainan City | Taiwan | |||
8 | Tainan | Taiwan | |||
9 | Taipei City | Taiwan | |||
10 | Taipei | Taiwan | |||
11 | Taoyuan | Taiwan |
Sponsors and Collaborators
- Gilead Sciences
Investigators
- Study Director: Gilead Study Director, Gilead Sciences
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GS-US-337-1655
Study Results
Participant Flow
Recruitment Details | Participants were enrolled at study sites in Taiwan. The first participant was screened on 22 December 2015. The last study visit occurred on 07 November 2018. |
---|---|
Pre-assignment Detail | 135 participants were screened. |
Arm/Group Title | LDV/SOF FDC |
---|---|
Arm/Group Description | Ledipasvir/sofosbuvir (LDV/SOF) (90/400 mg) fixed-dose combination (FDC) tablet orally once daily for 12 weeks. |
Period Title: Overall Study | |
STARTED | 111 |
COMPLETED | 108 |
NOT COMPLETED | 3 |
Baseline Characteristics
Arm/Group Title | LDV/SOF FDC |
---|---|
Arm/Group Description | LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks. |
Overall Participants | 111 |
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
55
(9.3)
|
Sex: Female, Male (Count of Participants) | |
Female |
69
62.2%
|
Male |
42
37.8%
|
Race/Ethnicity, Customized (Count of Participants) | |
Asian |
111
100%
|
Race/Ethnicity, Customized (Count of Participants) | |
Not Hispanic or Latino |
99
89.2%
|
Not Permitted |
12
10.8%
|
IL28b Status (Count of Participants) | |
CC |
85
76.6%
|
CT |
26
23.4%
|
HCV RNA (log10 IU/mL) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [log10 IU/mL] |
5.9
(0.73)
|
HCV RNA Category (Count of Participants) | |
< 800,000 IU/mL |
44
39.6%
|
≥ 800,000 IU/mL |
67
60.4%
|
Cirrhosis status (Count of Participants) | |
Absence |
93
83.8%
|
Presence |
18
16.2%
|
Fibroscan Score (kPa) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [kPa] |
9.3
(7.05)
|
Hepatitis B Virus (HBV) DNA (log10 IU/mL) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [log10 IU/mL] |
2.1
(0.92)
|
Plasma HBV DNA (IU/mL) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [IU/mL] |
9423.1
(69641.90)
|
HBsAg (IU/mL) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [IU/mL] |
578.6
(1113.56)
|
Serum Lysyl Oxidase-Like 2 (LOXL-2) Level (pg/mL) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [pg/mL] |
98
(64.4)
|
HCV Genotype (Count of Participants) | |
Genotype 1 |
1
0.9%
|
Genotype 1a |
3
2.7%
|
Genotype 1b |
64
57.7%
|
Genotype 2 |
43
38.7%
|
Outcome Measures
Title | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) |
---|---|
Description | SVR12 was defined as HCV RNA < the lower limit of quantification (LLOQ; 15 IU/mL) at 12 weeks after stopping study treatment. |
Time Frame | Posttreatment Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set included all participants who were enrolled and received at least 1 dose of study drug. |
Arm/Group Title | LDV/SOF FDC |
---|---|
Arm/Group Description | LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks. |
Measure Participants | 111 |
Genotype 1 |
100.0
90.1%
|
Genotype 2 |
100.0
90.1%
|
Total |
100.0
90.1%
|
Title | Percentage of Participants With Any Adverse Event Leading to Permanent Discontinuation of Study Drug |
---|---|
Description | |
Time Frame | First dose date up to 12 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Safety Analysis Set included participants who received at least 1 dose of study drug. |
Arm/Group Title | LDV/SOF FDC |
---|---|
Arm/Group Description | LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks. |
Measure Participants | 111 |
Number [percentage of participants] |
0.0
0%
|
Title | Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) |
---|---|
Description | SVR4 was defined as HCV RNA < LLOQ (15 IU/mL) at 4 weeks after stopping study treatment. |
Time Frame | Posttreatment Week 4 |
Outcome Measure Data
Analysis Population Description |
---|
Participants in Full Analysis Set were analyzed. |
Arm/Group Title | LDV/SOF FDC |
---|---|
Arm/Group Description | LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks. |
Measure Participants | 111 |
Number (95% Confidence Interval) [percentage of participants] |
100.0
90.1%
|
Title | Percentage of Participants With HCV RNA < LLOQ While on Treatment |
---|---|
Description | LLOQ = 15 IU/mL |
Time Frame | Weeks 1, 2, 4, 8, and 12 |
Outcome Measure Data
Analysis Population Description |
---|
Participants in Full Analysis Set were analyzed. |
Arm/Group Title | LDV/SOF FDC |
---|---|
Arm/Group Description | LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks. |
Measure Participants | 111 |
Week 1 |
33.3
30%
|
Week 2 |
82.0
73.9%
|
Week 4 |
100.0
90.1%
|
Week 8 |
100.0
90.1%
|
Week 12 |
100.0
90.1%
|
Title | Percentage of Participants With HCV RNA < LLOQ at Posttreatment Weeks 24, 36, 48, 60, 72, 84, 96, and 108 |
---|---|
Description | LLOQ = 15 IU/mL |
Time Frame | Posttreatment Weeks 24, 36, 48, 60, 72, 84, 96, and 108 |
Outcome Measure Data
Analysis Population Description |
---|
Participants in Full Analysis Set with available data were analyzed. |
Arm/Group Title | LDV/SOF FDC |
---|---|
Arm/Group Description | LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks. |
Measure Participants | 111 |
Posttreatment Week 24 |
100
90.1%
|
Posttreatment Week 36 |
100
90.1%
|
Posttreatment Week 48 |
100
90.1%
|
Posttreatment Week 60 |
100
90.1%
|
Posttreatment Week 72 |
100
90.1%
|
Posttreatment Week 84 |
100
90.1%
|
Posttreatment Week 96 |
100
90.1%
|
Posttreatment Week 108 |
100
90.1%
|
Title | HCV RNA Change From Baseline While on Treatment |
---|---|
Description | |
Time Frame | Weeks 1, 2, 4, 8, and 12 |
Outcome Measure Data
Analysis Population Description |
---|
Participants in Full Analysis Set were analyzed. |
Arm/Group Title | LDV/SOF FDC |
---|---|
Arm/Group Description | LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks. |
Measure Participants | 111 |
Change at Week 1 |
-4.14
(0.551)
|
Change at Week 2 |
-4.63
(0.702)
|
Change at Week 4 |
-4.73
(0.727)
|
Change at Week 8 |
-4.73
(0.727)
|
Change at Week 12 |
-4.73
(0.727)
|
Title | Percentage of Participants With Virologic Failure |
---|---|
Description | Virologic failure was defined as : Breakthrough (confirmed HCV RNA ≥ LLOQ [15 IU/mL] after having previously had HCV RNA < LLOQ while on treatment), or Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment), or Relapse (HCV RNA ≥ LLOQ during the post-treatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available post-treatment measurement) |
Time Frame | First dose date up to Posttreatment Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Participants in Full Analysis Set were analyzed. |
Arm/Group Title | LDV/SOF FDC |
---|---|
Arm/Group Description | LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks. |
Measure Participants | 111 |
Number [percentage of participants] |
0
0%
|
Title | Plasma HBV DNA Change From Baseline While on Treatment |
---|---|
Description | |
Time Frame | Weeks 1, 2, 4, 8, and 12 |
Outcome Measure Data
Analysis Population Description |
---|
Participants in Full Analysis Set with available data were analyzed. |
Arm/Group Title | LDV/SOF FDC |
---|---|
Arm/Group Description | LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks. |
Measure Participants | 111 |
Change at Week 1 |
-0.06
(0.237)
|
Change at Week 2 |
0.08
(0.366)
|
Change at Week 4 |
0.37
(0.705)
|
Change at Week 8 |
0.51
(0.906)
|
Change at Week 12 |
0.24
(0.746)
|
Title | Plasma HBV DNA Change From Baseline at Posttreatment Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, and 108 |
---|---|
Description | |
Time Frame | Posttreatment Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, and 108 |
Outcome Measure Data
Analysis Population Description |
---|
Participants in Full Analysis Set with available data were analyzed. |
Arm/Group Title | LDV/SOF FDC |
---|---|
Arm/Group Description | LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks. |
Measure Participants | 111 |
Change at Posttreatment Week 4 |
0.49
(0.727)
|
Change at Posttreatment Week 12 |
0.66
(0.955)
|
Change at Posttreatment Week 24 |
0.56
(1.036)
|
Change at Posttreatment Week 36 |
0.67
(1.190)
|
Change at Posttreatment Week 48 |
0.68
(1.269)
|
Change at Posttreatment Week 60 |
0.70
(1.399)
|
Change at Posttreatment Week 72 |
0.55
(1.131)
|
Change at Posttreatment Week 84 |
0.50
(1.008)
|
Change at Posttreatment Week 96 |
0.41
(0.963)
|
Change at Posttreatment Week 108 |
0.38
(0.923)
|
Title | HBsAg Level Change From Baseline While on Treatment |
---|---|
Description | |
Time Frame | Weeks 1, 2, 4, 8, and 12 |
Outcome Measure Data
Analysis Population Description |
---|
Participants in Full Analysis Set with available data were analyzed. |
Arm/Group Title | LDV/SOF FDC |
---|---|
Arm/Group Description | LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks. |
Measure Participants | 111 |
Change at Week 1 |
-0.14
(0.184)
|
Change at Week 2 |
-0.18
(0.181)
|
Change at Week 4 |
-0.25
(0.185)
|
Change at Week 8 |
-0.41
(0.234)
|
Change at Week 12 |
-0.47
(0.266)
|
Title | HBsAg Level Change From Baseline at Posttreatment Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, and 108 |
---|---|
Description | |
Time Frame | Posttreatment Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, and 108 |
Outcome Measure Data
Analysis Population Description |
---|
Participants in Full Analysis Set with available data were analyzed. |
Arm/Group Title | LDV/SOF FDC |
---|---|
Arm/Group Description | LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks. |
Measure Participants | 111 |
Change at Posttreatment Week 4 |
-0.16
(0.347)
|
Change at Posttreatment Week 12 |
-0.01
(0.338)
|
Change at Posttreatment Week 24 |
-0.02
(0.405)
|
Change at Posttreatment Week 36 |
-0.07
(0.484)
|
Change at Posttreatment Week 48 |
-0.10
(0.526)
|
Change at Posttreatment Week 60 |
-0.16
(0.664)
|
Change at Posttreatment Week 72 |
-0.20
(0.619)
|
Change at Posttreatment Week 84 |
-0.25
(0.608)
|
Change at Posttreatment Week 96 |
-0.32
(0.618)
|
Change at Posttreatment Week 108 |
-0.37
(0.658)
|
Title | Serum LOXL-2 Level Change From Baseline While on Treatment |
---|---|
Description | |
Time Frame | Weeks 1, 2, 4, 8, and 12 |
Outcome Measure Data
Analysis Population Description |
---|
Participants in Full Analysis Set with available data were analyzed. |
Arm/Group Title | LDV/SOF FDC |
---|---|
Arm/Group Description | LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks. |
Measure Participants | 111 |
Change at Week 1 |
-2
(29.4)
|
Change at Week 2 |
-6
(26.9)
|
Change at Week 4 |
-15
(27.8)
|
Change at Week 8 |
-22
(36.6)
|
Change at Week 12 |
-27
(36.0)
|
Title | Serum LOXL-2 Level Change From Baseline at Posttreatment Weeks 4, 12, and 36 |
---|---|
Description | |
Time Frame | Posttreatment Weeks 4, 12, and 36 |
Outcome Measure Data
Analysis Population Description |
---|
Participants in Full Analysis Set were analyzed. |
Arm/Group Title | LDV/SOF FDC |
---|---|
Arm/Group Description | LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks. |
Measure Participants | 111 |
Change at Posttreatment Week 4 |
-30
(45.0)
|
Change at Posttreatment Week 12 |
-32
(51.8)
|
Change at Posttreatment Week 36 |
-41
(53.0)
|
Title | Percentage of Participants That Required HBV Therapy During the Study |
---|---|
Description | |
Time Frame | First dose date up to Posttreatment Week 108 |
Outcome Measure Data
Analysis Population Description |
---|
Participants in Full Analysis Set were analyzed. |
Arm/Group Title | LDV/SOF FDC |
---|---|
Arm/Group Description | LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks. |
Measure Participants | 111 |
Number [percentage of participants] |
7.2
6.5%
|
Title | Fibrosis Status as Assessed by Fibroscan Score at Posttreatment Weeks 12, 60, and 108 |
---|---|
Description | FibroScan is a non-invasive device that assesses the hardness (or stiffness) of the liver using the technique of transient elastography. FibroScan results range from 2.5 kPa to 75 kPa with higher scores indicating greater liver stiffness. Per protocol, cirrhosis status was determined as follows: Presence of cirrhosis = FibroScan result of > 12.5 kPa Absence of cirrhosis = FibroScan result of ≤ 12.5 kPa |
Time Frame | Posttreatment Weeks 12, 60, and 108 |
Outcome Measure Data
Analysis Population Description |
---|
Participants in Full Analysis Set with available data were analyzed. |
Arm/Group Title | LDV/SOF FDC |
---|---|
Arm/Group Description | LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks. |
Measure Participants | 111 |
Posttreatment Week 12 |
8.0
(7.01)
|
Posttreatment Week 60 |
7.2
(4.99)
|
Posttreatment Week 108 |
7.1
(4.79)
|
Title | Percentage of Participants That Develop Hepatocellular Carcinoma (HCC) During the Study |
---|---|
Description | |
Time Frame | First dose date up to Posttreatment Week 108 |
Outcome Measure Data
Analysis Population Description |
---|
Participants in Full Analysis Set were analyzed. |
Arm/Group Title | LDV/SOF FDC |
---|---|
Arm/Group Description | LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks. |
Measure Participants | 111 |
Number [percentage of participants] |
0.0
0%
|
Adverse Events
Time Frame | Adverse Events: First dose date up to 12 weeks plus 30 days; All-Cause Mortality: First dose date up to maximum 3 years | |
---|---|---|
Adverse Event Reporting Description | Safety Analysis Set included participants who received at least 1 dose of study drug. | |
Arm/Group Title | LDV/SOF FDC | |
Arm/Group Description | LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks. | |
All Cause Mortality |
||
LDV/SOF FDC | ||
Affected / at Risk (%) | # Events | |
Total | 2/111 (1.8%) | |
Serious Adverse Events |
||
LDV/SOF FDC | ||
Affected / at Risk (%) | # Events | |
Total | 4/111 (3.6%) | |
Gastrointestinal disorders | ||
Duodenal ulcer | 1/111 (0.9%) | |
Injury, poisoning and procedural complications | ||
Meniscus injury | 1/111 (0.9%) | |
Post procedural haemorrhage | 1/111 (0.9%) | |
Nervous system disorders | ||
Optic neuritis | 1/111 (0.9%) | |
Other (Not Including Serious) Adverse Events |
||
LDV/SOF FDC | ||
Affected / at Risk (%) | # Events | |
Total | 24/111 (21.6%) | |
General disorders | ||
Fatigue | 8/111 (7.2%) | |
Infections and infestations | ||
Upper respiratory tract infection | 9/111 (8.1%) | |
Nervous system disorders | ||
Headache | 11/111 (9.9%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years
Results Point of Contact
Name/Title | Gilead Clinical Study Information Center |
---|---|
Organization | Gilead Sciences |
Phone | 1-833-445-3230 (GILEAD-0) |
GileadClinicalTrials@gilead.com |
- GS-US-337-1655