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Trial record 3 of 115 for:    "Viral Infectious Disease" | "Ledipasvir"

Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination in Adults With Chronic HCV and HBV Coinfection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02613871
Recruitment Status : Completed
First Posted : November 25, 2015
Results First Posted : February 13, 2018
Last Update Posted : November 15, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hepatitis C Virus Infection
Intervention Drug: LDV/SOF
Enrollment 111
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 Details 135 participants were screened.
Arm/Group Title LDV/SOF FDC
Hide 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
Reason Not Completed
Death             2
Withdrew Consent             1
Arm/Group Title LDV/SOF FDC
Hide Arm/Group Description LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks.
Overall Number of Baseline Participants 111
Hide Baseline Analysis Population Description
Safety Analysis Set included participants who received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 111 participants
55  (9.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 111 participants
Female 69
Male 42
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Asian Number Analyzed 111 participants
111
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Ethnicity Number Analyzed 111 participants
Not Hispanic or Latino 99
Not Permitted 12
IL28b Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 111 participants
CC 85
CT 26
[1]
Measure Description: CC and CT alleles are different forms of the IL28b gene.
HCV RNA  
Mean (Standard Deviation)
Unit of measure:  Log10 IU/mL
Number Analyzed 111 participants
5.9  (0.73)
HCV RNA Category  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 111 participants
< 800,000 IU/mL 44
≥ 800,000 IU/mL 67
Cirrhosis status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 111 participants
Absence 93
Presence 18
Fibroscan Score   [1] 
Mean (Standard Deviation)
Unit of measure:  kPa
Number Analyzed 111 participants
9.3  (7.05)
[1]
Measure 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
Hepatitis B Virus (HBV) DNA  
Mean (Standard Deviation)
Unit of measure:  Log10 IU/mL
Number Analyzed 111 participants
2.1  (0.92)
Plasma HBV DNA  
Mean (Standard Deviation)
Unit of measure:  IU/mL
Number Analyzed 111 participants
9423.1  (69641.90)
HBsAg  
Mean (Standard Deviation)
Unit of measure:  IU/mL
Number Analyzed 111 participants
578.6  (1113.56)
Serum Lysyl Oxidase-Like 2 (LOXL-2) Level  
Mean (Standard Deviation)
Unit of measure:  pg/mL
Number Analyzed 111 participants
98  (64.4)
HCV Genotype   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 111 participants
Genotype 1 1
Genotype 1a 3
Genotype 1b 64
Genotype 2 43
[1]
Measure Description: HCV Genotype 1 indicates genotype 1 with no confirmed subtype (eg, 1a, 1b or mixed 1a/1b).
1.Primary Outcome
Title Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks.
Overall Number of Participants Analyzed 111
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Genotype 1 Number Analyzed 68 participants
100.0
(94.7 to 100.0)
Genotype 2 Number Analyzed 43 participants
100.0
(91.8 to 100.0)
Total Number Analyzed 111 participants
100.0
(96.7 to 100.0)
2.Primary Outcome
Title Percentage of Participants With Any Adverse Event Leading to Permanent Discontinuation of Study Drug
Hide Description [Not Specified]
Time Frame First dose date up to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set included participants who received at least 1 dose of study drug.
Arm/Group Title LDV/SOF FDC
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks.
Overall Number of Participants Analyzed 111
Measure Type: Number
Unit of Measure: percentage of participants
0.0
3.Secondary Outcome
Title Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)
Hide Description SVR4 was defined as HCV RNA < LLOQ (15 IU/mL) at 4 weeks after stopping study treatment.
Time Frame Posttreatment Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Full Analysis Set were analyzed.
Arm/Group Title LDV/SOF FDC
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks.
Overall Number of Participants Analyzed 111
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
100.0
(96.7 to 100.0)
4.Secondary Outcome
Title Percentage of Participants With HCV RNA < LLOQ While on Treatment
Hide Description LLOQ = 15 IU/mL
Time Frame Weeks 1, 2, 4, 8, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Full Analysis Set were analyzed.
Arm/Group Title LDV/SOF FDC
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks.
Overall Number of Participants Analyzed 111
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 1
33.3
(24.7 to 42.9)
Week 2
82.0
(73.6 to 88.6)
Week 4
100.0
(96.7 to 100.0)
Week 8
100.0
(96.7 to 100.0)
Week 12
100.0
(96.7 to 100.0)
5.Secondary Outcome
Title Percentage of Participants With HCV RNA < LLOQ at Posttreatment Weeks 24, 36, 48, 60, 72, 84, 96, and 108
Hide Description LLOQ = 15 IU/mL
Time Frame Posttreatment Weeks 24, 36, 48, 60, 72, 84, 96, and 108
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Full Analysis Set with available data were analyzed.
Arm/Group Title LDV/SOF FDC
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks.
Overall Number of Participants Analyzed 111
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Posttreatment Week 24 Number Analyzed 111 participants
100
(96.7 to 100)
Posttreatment Week 36 Number Analyzed 111 participants
100
(96.7 to 100)
Posttreatment Week 48 Number Analyzed 111 participants
100
(96.7 to 100)
Posttreatment Week 60 Number Analyzed 111 participants
100
(96.7 to 100)
Posttreatment Week 72 Number Analyzed 110 participants
100
(96.7 to 100)
Posttreatment Week 84 Number Analyzed 109 participants
100
(96.7 to 100)
Posttreatment Week 96 Number Analyzed 108 participants
100
(96.6 to 100)
Posttreatment Week 108 Number Analyzed 108 participants
100
(96.6 to 100)
6.Secondary Outcome
Title HCV RNA Change From Baseline While on Treatment
Hide Description [Not Specified]
Time Frame Weeks 1, 2, 4, 8, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Full Analysis Set were analyzed.
Arm/Group Title LDV/SOF FDC
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks.
Overall Number of Participants Analyzed 111
Mean (Standard Deviation)
Unit of Measure: log10 IU/mL
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)
7.Secondary Outcome
Title Percentage of Participants With Virologic Failure
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Full Analysis Set were analyzed.
Arm/Group Title LDV/SOF FDC
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks.
Overall Number of Participants Analyzed 111
Measure Type: Number
Unit of Measure: percentage of participants
0
8.Secondary Outcome
Title Plasma HBV DNA Change From Baseline While on Treatment
Hide Description [Not Specified]
Time Frame Weeks 1, 2, 4, 8, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Full Analysis Set with available data were analyzed.
Arm/Group Title LDV/SOF FDC
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks.
Overall Number of Participants Analyzed 111
Mean (Standard Deviation)
Unit of Measure: log10 IU/mL
Change at Week 1 Number Analyzed 111 participants
-0.06  (0.237)
Change at Week 2 Number Analyzed 111 participants
0.08  (0.366)
Change at Week 4 Number Analyzed 111 participants
0.37  (0.705)
Change at Week 8 Number Analyzed 111 participants
0.51  (0.906)
Change at Week 12 Number Analyzed 106 participants
0.24  (0.746)
9.Secondary Outcome
Title Plasma HBV DNA Change From Baseline at Posttreatment Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, and 108
Hide Description [Not Specified]
Time Frame Posttreatment Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, and 108
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Full Analysis Set with available data were analyzed.
Arm/Group Title LDV/SOF FDC
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks.
Overall Number of Participants Analyzed 111
Mean (Standard Deviation)
Unit of Measure: log10 IU/mL
Change at Posttreatment Week 4 Number Analyzed 111 participants
0.49  (0.727)
Change at Posttreatment Week 12 Number Analyzed 111 participants
0.66  (0.955)
Change at Posttreatment Week 24 Number Analyzed 111 participants
0.56  (1.036)
Change at Posttreatment Week 36 Number Analyzed 111 participants
0.67  (1.190)
Change at Posttreatment Week 48 Number Analyzed 111 participants
0.68  (1.269)
Change at Posttreatment Week 60 Number Analyzed 111 participants
0.70  (1.399)
Change at Posttreatment Week 72 Number Analyzed 110 participants
0.55  (1.131)
Change at Posttreatment Week 84 Number Analyzed 109 participants
0.50  (1.008)
Change at Posttreatment Week 96 Number Analyzed 108 participants
0.41  (0.963)
Change at Posttreatment Week 108 Number Analyzed 108 participants
0.38  (0.923)
10.Secondary Outcome
Title HBsAg Level Change From Baseline While on Treatment
Hide Description [Not Specified]
Time Frame Weeks 1, 2, 4, 8, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Full Analysis Set with available data were analyzed.
Arm/Group Title LDV/SOF FDC
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks.
Overall Number of Participants Analyzed 111
Mean (Standard Deviation)
Unit of Measure: log10 IU/mL
Change at Week 1 Number Analyzed 111 participants
-0.14  (0.184)
Change at Week 2 Number Analyzed 111 participants
-0.18  (0.181)
Change at Week 4 Number Analyzed 111 participants
-0.25  (0.185)
Change at Week 8 Number Analyzed 111 participants
-0.41  (0.234)
Change at Week 12 Number Analyzed 106 participants
-0.47  (0.266)
11.Secondary Outcome
Title HBsAg Level Change From Baseline at Posttreatment Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, and 108
Hide Description [Not Specified]
Time Frame Posttreatment Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, and 108
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Full Analysis Set with available data were analyzed.
Arm/Group Title LDV/SOF FDC
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks.
Overall Number of Participants Analyzed 111
Mean (Standard Deviation)
Unit of Measure: log10 IU/mL
Change at Posttreatment Week 4 Number Analyzed 111 participants
-0.16  (0.347)
Change at Posttreatment Week 12 Number Analyzed 111 participants
-0.01  (0.338)
Change at Posttreatment Week 24 Number Analyzed 111 participants
-0.02  (0.405)
Change at Posttreatment Week 36 Number Analyzed 111 participants
-0.07  (0.484)
Change at Posttreatment Week 48 Number Analyzed 111 participants
-0.10  (0.526)
Change at Posttreatment Week 60 Number Analyzed 111 participants
-0.16  (0.664)
Change at Posttreatment Week 72 Number Analyzed 110 participants
-0.20  (0.619)
Change at Posttreatment Week 84 Number Analyzed 109 participants
-0.25  (0.608)
Change at Posttreatment Week 96 Number Analyzed 108 participants
-0.32  (0.618)
Change at Posttreatment Week 108 Number Analyzed 108 participants
-0.37  (0.658)
12.Secondary Outcome
Title Serum LOXL-2 Level Change From Baseline While on Treatment
Hide Description [Not Specified]
Time Frame Weeks 1, 2, 4, 8, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Full Analysis Set with available data were analyzed.
Arm/Group Title LDV/SOF FDC
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks.
Overall Number of Participants Analyzed 111
Mean (Standard Deviation)
Unit of Measure: pg/mL
Change at Week 1 Number Analyzed 110 participants
-2  (29.4)
Change at Week 2 Number Analyzed 111 participants
-6  (26.9)
Change at Week 4 Number Analyzed 111 participants
-15  (27.8)
Change at Week 8 Number Analyzed 111 participants
-22  (36.6)
Change at Week 12 Number Analyzed 106 participants
-27  (36.0)
13.Secondary Outcome
Title Serum LOXL-2 Level Change From Baseline at Posttreatment Weeks 4, 12, and 36
Hide Description [Not Specified]
Time Frame Posttreatment Weeks 4, 12, and 36
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Full Analysis Set were analyzed.
Arm/Group Title LDV/SOF FDC
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks.
Overall Number of Participants Analyzed 111
Mean (Standard Deviation)
Unit of Measure: pg/mL
Change at Posttreatment Week 4 -30  (45.0)
Change at Posttreatment Week 12 -32  (51.8)
Change at Posttreatment Week 36 -41  (53.0)
14.Secondary Outcome
Title Percentage of Participants That Required HBV Therapy During the Study
Hide Description [Not Specified]
Time Frame First dose date up to Posttreatment Week 108
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Full Analysis Set were analyzed.
Arm/Group Title LDV/SOF FDC
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks.
Overall Number of Participants Analyzed 111
Measure Type: Number
Unit of Measure: percentage of participants
7.2
15.Secondary Outcome
Title Fibrosis Status as Assessed by Fibroscan Score at Posttreatment Weeks 12, 60, and 108
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Full Analysis Set with available data were analyzed.
Arm/Group Title LDV/SOF FDC
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks.
Overall Number of Participants Analyzed 111
Mean (Standard Deviation)
Unit of Measure: kPa
Posttreatment Week 12 Number Analyzed 111 participants
8.0  (7.01)
Posttreatment Week 60 Number Analyzed 111 participants
7.2  (4.99)
Posttreatment Week 108 Number Analyzed 108 participants
7.1  (4.79)
16.Secondary Outcome
Title Percentage of Participants That Develop Hepatocellular Carcinoma (HCC) During the Study
Hide Description [Not Specified]
Time Frame First dose date up to Posttreatment Week 108
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Full Analysis Set were analyzed.
Arm/Group Title LDV/SOF FDC
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet orally once daily for 12 weeks.
Overall Number of Participants Analyzed 111
Measure Type: Number
Unit of Measure: percentage of participants
0.0
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
Hide 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 (%)
Total   2/111 (1.80%) 
Show Serious Adverse Events Hide Serious Adverse Events
LDV/SOF FDC
Affected / at Risk (%)
Total   4/111 (3.60%) 
Gastrointestinal disorders   
Duodenal ulcer  1  1/111 (0.90%) 
Injury, poisoning and procedural complications   
Meniscus injury  1  1/111 (0.90%) 
Post procedural haemorrhage  1  1/111 (0.90%) 
Nervous system disorders   
Optic neuritis  1  1/111 (0.90%) 
1
Term from vocabulary, MedDRA 21.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
LDV/SOF FDC
Affected / at Risk (%)
Total   24/111 (21.62%) 
General disorders   
Fatigue  1  8/111 (7.21%) 
Infections and infestations   
Upper respiratory tract infection  1  9/111 (8.11%) 
Nervous system disorders   
Headache  1  11/111 (9.91%) 
1
Term from vocabulary, MedDRA 21.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.

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
Layout table for Results Point of Contact information
Name/Title: Gilead Clinical Study Information Center
Organization: Gilead Sciences
Phone: 1-833-445-3230 (GILEAD-0)
EMail: GileadClinicalTrials@gilead.com
Publications of Results:
Liu CJ, Chuang WL, Sheen IS, Wang HY, Chen CY, Tseng KC, et al. Ledipasvir/Sofosbuvir for 12 Weeks Is Safe and Effective in Patients With Chronic Hepatitis C and Hepatitis B Coinfection: a Phase 3 Study in Taiwan [Poster SAT-243]. EASL: The International Liver Congress; 2019 10-14 April; Vienna, Austria.
Liu CJ, Chuang WL, Sheen IS, Wang HY, Chen CY, Tseng KC, et al. Declines in HBsAg Levels Observed During Treatment With Ledispavir/Sofosbuvir in Patients With Chronic Hepatitis B Virus and Hepatitis C Virus Infection [Poster 1083]. The Liver Meeting® 2017 - The 68th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD); 2017 20-24 October; Washington, D. C.
Liu CJ, Chuang WL, Sheen IS, Wang HY, Chen CY, Tseng KC, et al. Ledipasvir/Sofosbuvir for 12 Weeks Is Safe and Effective in Patients with Chronic Hepatitis C and Hepatitis B Coinfection: A Phase 3 Study in Taiwan [Presentation]. The International Liver Congress™ 2017: European Association for the Study of the Liver (EASL); 2017 19-23 April; Amsterdam, the Netherlands.
Layout table for additonal information
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02613871     History of Changes
Other Study ID Numbers: GS-US-337-1655
First Submitted: November 23, 2015
First Posted: November 25, 2015
Results First Submitted: January 3, 2018
Results First Posted: February 13, 2018
Last Update Posted: November 15, 2019