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Trial record 8 of 115 for:    "Viral Infectious Disease" | "Ledipasvir"

Safety and Efficacy of Ledipasvir/Sofosbuvir in Adults With Chronic HCV Infection

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ClinicalTrials.gov Identifier: NCT02472886
Recruitment Status : Completed
First Posted : June 16, 2015
Results First Posted : May 10, 2017
Last Update Posted : November 16, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hepatitis C Virus Infection
Interventions Drug: LDV/SOF
Drug: RBV
Enrollment 153
Recruitment Details Participants were enrolled at study sites in Russia and Estonia. The first participant was screened on 17 June 2015. The last study visit occurred on 30 June 2016.
Pre-assignment Details 169 participants were screened.
Arm/Group Title LDV/SOF 8 Weeks (TN, HCV-monoinfected) LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected)
Hide Arm/Group Description Ledipasvir/sofosbuvir (LDV/SOF; Harvoni®) (90/400 mg) fixed dose combination (FDC) tablet once daily for 8 weeks in treatment-naive (TN) participants with genotype 1 HCV infection without cirrhosis LDV/SOF (90/400 mg) FDC tablet once daily for 8 weeks in treatment naive participants with genotype 1 HCV infection without cirrhosis and coinfected with HIV-1 LDV/SOF (90/400 mg) FDC tablet once daily + weight-based ribavirin (RBV) (1000-1200 mg in a divided daily dose) for 12 weeks in treatment-experienced (TE) participants with genotype 1 or 3 HCV infection who failed to achieve sustained virologic response (SVR) in a previous Gilead sofosbuvir (SOF) study
Period Title: Overall Study
Started 67 59 27
Completed 67 57 26
Not Completed 0 2 1
Reason Not Completed
Lack of Efficacy             0             2             1
Arm/Group Title LDV/SOF 8 Weeks (TN, HCV-monoinfected) LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected) Total
Hide Arm/Group Description LDV/SOF(90/400 mg) FDC tablet once daily for 8 weeks in treatment-naive (TN) participants with genotype 1 HCV infection without cirrhosis LDV/SOF (90/400 mg) FDC tablet once daily for 8 weeks in treatment naive participants with genotype 1 HCV infection without cirrhosis and coinfected with HIV-1 LDV/SOF (90/400 mg) FDC tablet once daily + weight-based ribavirin (RBV) (1000-1200 mg in a divided daily dose) for 12 weeks in treatment-experienced (TE) participants with genotype 1 or 3 HCV infection who failed to achieve SVR in a previous Gilead sofosbuvir study Total of all reporting groups
Overall Number of Baseline Participants 67 59 27 153
Hide Baseline Analysis Population Description
Safety Analysis Set included all participants who received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 67 participants 59 participants 27 participants 153 participants
42  (12.6) 34  (5.5) 47  (11.2) 40  (11.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 67 participants 59 participants 27 participants 153 participants
Female
33
  49.3%
25
  42.4%
9
  33.3%
67
  43.8%
Male
34
  50.7%
34
  57.6%
18
  66.7%
86
  56.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 67 participants 59 participants 27 participants 153 participants
White
66
  98.5%
59
 100.0%
27
 100.0%
152
  99.3%
Asian
1
   1.5%
0
   0.0%
0
   0.0%
1
   0.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Not Hispanic or Latino Number Analyzed 67 participants 59 participants 27 participants 153 participants
67
 100.0%
59
 100.0%
27
 100.0%
153
 100.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 67 participants 59 participants 27 participants 153 participants
Russian Federation
61
  91.0%
47
  79.7%
27
 100.0%
135
  88.2%
Estonia
6
   9.0%
12
  20.3%
0
   0.0%
18
  11.8%
IL28b Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 67 participants 59 participants 27 participants 153 participants
CC
17
  25.4%
9
  15.3%
7
  25.9%
33
  21.6%
CT
41
  61.2%
41
  69.5%
18
  66.7%
100
  65.4%
TT
9
  13.4%
9
  15.3%
2
   7.4%
20
  13.1%
[1]
Measure Description: The CC, CT, and TT alleles are different forms of the IL28b gene.
HCV RNA  
Mean (Standard Deviation)
Unit of measure:  Log10 IU/mL
Number Analyzed 67 participants 59 participants 27 participants 153 participants
5.9  (0.72) 6.1  (0.54) 6.3  (0.67) 6.0  (0.66)
HCV RNA Category  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 67 participants 59 participants 27 participants 153 participants
< 800,000 IU/mL
29
  43.3%
23
  39.0%
8
  29.6%
60
  39.2%
≥ 800,000 IU/mL
38
  56.7%
36
  61.0%
19
  70.4%
93
  60.8%
Cirrhosis Status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 67 participants 59 participants 27 participants 153 participants
No
67
 100.0%
59
 100.0%
17
  63.0%
143
  93.5%
Yes
0
   0.0%
0
   0.0%
10
  37.0%
10
   6.5%
1.Primary Outcome
Title Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)
Hide Description SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.
Time Frame Posttreatment Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included participants who were enrolled into the study and received at least 1 dose of study drug.
Arm/Group Title LDV/SOF 8 Weeks (TN, HCV-monoinfected) LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected)
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 8 weeks in treatment-naive (TN) participants with genotype 1 HCV infection without cirrhosis
LDV/SOF (90/400 mg) FDC tablet once daily for 8 weeks in treatment naive participants with genotype 1 HCV infection without cirrhosis and coinfected with HIV-1
LDV/SOF (90/400 mg) FDC tablet once daily + weight-based ribavirin (RBV) (1000-1200 mg in a divided daily dose) for 12 weeks in treatment-experienced (TE) participants with genotype 1 or 3 HCV infection who failed to achieve SVR in a previous Gilead sofosbuvir study
Overall Number of Participants Analyzed 67 59 27
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
100.0
(94.6 to 100.0)
96.6
(88.3 to 99.6)
96.3
(81.0 to 99.9)
2.Primary Outcome
Title Percentage of Participants Who Discontinued Study Drug Due to Any Adverse Event (AE)
Hide Description [Not Specified]
Time Frame Up to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set
Arm/Group Title LDV/SOF 8 Weeks (TN, HCV-monoinfected) LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected)
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 8 weeks in treatment-naive participants with genotype 1 HCV infection without cirrhosis
LDV/SOF (90/400 mg) FDC tablet once daily for 8 weeks in treatment naive participants with genotype 1 HCV infection without cirrhosis and coinfected with HIV-1
LDV/SOF (90/400 mg) FDC tablet once daily + weight-based ribavirin (RBV) (1000-1200 mg in a divided daily dose) for 12 weeks in treatment-experienced (TE) participants with genotype 1 or 3 HCV infection who failed to achieve SVR in a previous Gilead sofosbuvir study
Overall Number of Participants Analyzed 67 59 27
Measure Type: Number
Unit of Measure: percentage of participants
0 0 0
3.Secondary Outcome
Title Percentage of Participants With Sustained Virologic Response (SVR) at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
Hide Description SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
Time Frame Posttreatment Weeks 4 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title LDV/SOF 8 Weeks (TN, HCV-monoinfected) LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected)
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 8 weeks in treatment-naive participants with genotype 1 HCV infection without cirrhosis
LDV/SOF (90/400 mg) FDC tablet once daily for 8 weeks in treatment naive participants with genotype 1 HCV infection without cirrhosis and coinfected with HIV-1
LDV/SOF (90/400 mg) FDC tablet once daily + weight-based ribavirin (RBV) (1000-1200 mg in a divided daily dose) for 12 weeks in treatment-experienced (TE) participants with genotype 1 or 3 HCV infection who failed to achieve SVR in a previous Gilead sofosbuvir study
Overall Number of Participants Analyzed 67 59 27
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
SVR4
100.0
(94.6 to 100.0)
96.6
(88.3 to 99.6)
96.3
(81.0 to 99.9)
SVR24
100.0
(94.6 to 100.0)
96.6
(88.3 to 99.6)
96.3
(81.0 to 99.9)
4.Secondary Outcome
Title Percentage of Participants With HCV RNA < LLOQ on Treatment
Hide Description [Not Specified]
Time Frame Up to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title LDV/SOF 8 Weeks (TN, HCV-monoinfected) LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected)
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 8 weeks in treatment-naive participants with genotype 1 HCV infection without cirrhosis
LDV/SOF (90/400 mg) FDC tablet once daily for 8 weeks in treatment naive participants with genotype 1 HCV infection without cirrhosis and coinfected with HIV-1
LDV/SOF (90/400 mg) FDC tablet once daily + weight-based ribavirin (RBV) (1000-1200 mg in a divided daily dose) for 12 weeks in treatment-experienced (TE) participants with genotype 1 or 3 HCV infection who failed to achieve SVR in a previous Gilead sofosbuvir study
Overall Number of Participants Analyzed 67 59 27
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 1
20.9
(11.9 to 32.6)
39.0
(26.5 to 52.6)
3.7
(0.1 to 19.0)
Week 2
65.7
(53.1 to 76.8)
69.5
(56.1 to 80.8)
59.3
(38.8 to 77.6)
Week 4
100.0
(94.6 to 100.0)
96.6
(88.3 to 99.6)
88.9
(70.8 to 97.6)
Week 8
100.0
(94.6 to 100.0)
98.3
(90.9 to 100.0)
100.0
(87.2 to 100.0)
Week 12
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
100.0
(87.2 to 100.0)
[1]
Treatment for this group was 8 weeks only.
5.Secondary Outcome
Title HCV RNA Change From Day 1
Hide Description [Not Specified]
Time Frame Up to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Full Analysis Set with available data were analyzed.
Arm/Group Title LDV/SOF 8 Weeks (TN, HCV-monoinfected) LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected)
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 8 weeks in treatment-naive participants with genotype 1 HCV infection without cirrhosis
LDV/SOF (90/400 mg) FDC tablet once daily for 8 weeks in treatment naive participants with genotype 1 HCV infection without cirrhosis and coinfected with HIV-1
LDV/SOF (90/400 mg) FDC tablet once daily + weight-based ribavirin (RBV) (1000-1200 mg in a divided daily dose) for 12 weeks in treatment-experienced (TE) participants with genotype 1 or 3 HCV infection who failed to achieve SVR in a previous Gilead sofosbuvir study
Overall Number of Participants Analyzed 67 59 27
Mean (Standard Deviation)
Unit of Measure: log10 IU/mL
Week 1 Number Analyzed 65 participants 58 participants 27 participants
-3.97  (0.675) -4.34  (0.626) -4.12  (0.582)
Week 2 Number Analyzed 67 participants 58 participants 27 participants
-4.50  (0.687) -4.76  (0.522) -4.83  (0.630)
Week 4 Number Analyzed 67 participants 59 participants 27 participants
-4.74  (0.723) -4.89  (0.534) -5.08  (0.642)
Week 8 Number Analyzed 67 participants 59 participants 27 participants
-4.74  (0.723) -4.91  (0.536) -5.11  (0.671)
Week 12 Number Analyzed 67 participants 59 participants 27 participants
NA [1]   (NA) NA [1]   (NA) -5.11  (0.671)
[1]
Treatment for this group was 8 weeks only.
6.Secondary Outcome
Title Percentage of Participants With Virologic Failure
Hide Description

Virologic failure was defined as

  • On-treatment virologic failure

    • confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment (ie, breakthrough),
    • confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment (ie, rebound), HCV RNA persistently ≥ LLOQ through 8 weeks of treatment (ie, nonresponse)
  • Relapse

    • HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement
Time Frame Up to Posttreatment Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title LDV/SOF 8 Weeks (TN, HCV-monoinfected) LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected)
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 8 weeks in treatment-naive participants with genotype 1 HCV infection without cirrhosiss
LDV/SOF (90/400 mg) FDC tablet once daily for 8 weeks in treatment naive participants with genotype 1 HCV infection without cirrhosis and coinfected with HIV-1
LDV/SOF (90/400 mg) FDC tablet once daily + weight-based ribavirin (RBV) (1000-1200 mg in a divided daily dose) for 12 weeks in treatment-experienced (TE) participants with genotype 1 or 3 HCV infection who failed to achieve SVR in a previous Gilead sofosbuvir study
Overall Number of Participants Analyzed 67 59 27
Measure Type: Number
Unit of Measure: percentage of participants
0 3.4 3.7
7.Secondary Outcome
Title Percentage of HIV/HCV- Coinfected Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment and at Posttreatment Week 4
Hide Description [Not Specified]
Time Frame Up to Posttreatment Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Safety Analysis Set (who had HIV RNA < 50 Copies/mL at baseline) with available data were analyzed.
Arm/Group Title LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected)
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 8 weeks in treatment naive participants with genotype 1 HCV infection without cirrhosis and coinfected with HIV-1
Overall Number of Participants Analyzed 45
Measure Type: Number
Unit of Measure: percentage of participants
Week 4 Number Analyzed 45 participants
100.0
Week 8 Number Analyzed 43 participants
100.0
Posttreatment Week 4 Number Analyzed 36 participants
97.2
8.Secondary Outcome
Title For HIV/HCV- Coinfected Participants, Change From Baseline in CD4 T-cell Count at the End of Treatment and Posttreatment Week 4
Hide Description [Not Specified]
Time Frame Up to Posttreatment Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Participant in the Safety analysis set (with or without prior antiretroviral (ARV) treatment) with available data were analyzed.
Arm/Group Title LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected, ARV- Naive) LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected, ARV Experienced)
Hide Arm/Group Description:
LDV/SOF (90/400 mg) FDC tablet once daily for 8 weeks in treatment naive participants with genotype 1 HCV infection without cirrhosis and coinfected with HIV-1. These participants did not receive any prior ARV therapy.
LDV/SOF (90/400 mg) FDC tablet once daily for 8 weeks in treatment naive participants with genotype 1 HCV infection without cirrhosis and coinfected with HIV-1. These participants were on a stable ARV regimen for at least 8 weeks prior to screening.
Overall Number of Participants Analyzed 44 9
Mean (Standard Deviation)
Unit of Measure: cells/µL
Change at Week 4 Number Analyzed 43 participants 9 participants
47  (120.5) 159  (114.9)
Change at Week 8 Number Analyzed 44 participants 9 participants
45  (122.7) 202  (178.1)
Change at Posttreatment Week 4 Number Analyzed 35 participants 5 participants
74  (117.8) 172  (114.1)
Time Frame Up to 12 weeks plus 30 days
Adverse Event Reporting Description Safety Analysis Set
 
Arm/Group Title LDV/SOF 8 Weeks (TN, HCV-monoinfected) LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected)
Hide Arm/Group Description LDV/SOF (90/400 mg) FDC tablet once daily for 8 weeks in treatment-naive (TN) participants with genotype 1 HCV infection without cirrhosis LDV/SOF (90/400 mg) FDC tablet once daily for 8 weeks in treatment naive participants with genotype 1 HCV infection without cirrhosis and coinfected with HIV-1 LDV/SOF (90/400 mg) FDC tablet once daily + weight-based ribavirin (RBV) (1000-1200 mg in a divided daily dose) for 12 weeks in treatment-experienced (TE) participants with genotype 1 or 3 HCV infection who failed to achieve SVR in a previous Gilead sofosbuvir study
All-Cause Mortality
LDV/SOF 8 Weeks (TN, HCV-monoinfected) LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/67 (0.00%)   0/59 (0.00%)   0/27 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
LDV/SOF 8 Weeks (TN, HCV-monoinfected) LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/67 (0.00%)   0/59 (0.00%)   0/27 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
LDV/SOF 8 Weeks (TN, HCV-monoinfected) LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/67 (7.46%)   2/59 (3.39%)   8/27 (29.63%) 
Gastrointestinal disorders       
Abdominal pain upper  1  1/67 (1.49%)  1/59 (1.69%)  2/27 (7.41%) 
Dyspepsia  1  0/67 (0.00%)  0/59 (0.00%)  3/27 (11.11%) 
General disorders       
Asthenia  1  1/67 (1.49%)  0/59 (0.00%)  2/27 (7.41%) 
Investigations       
Blood bilirubin increased  1  0/67 (0.00%)  0/59 (0.00%)  2/27 (7.41%) 
Nervous system disorders       
Headache  1  4/67 (5.97%)  0/59 (0.00%)  4/27 (14.81%) 
Psychiatric disorders       
Irritability  1  0/67 (0.00%)  1/59 (1.69%)  2/27 (7.41%) 
1
Term from vocabulary, MedDRA 19.0
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: Clinical Trial Disclosures
Organization: Gilead Sciences
EMail: ClinicalTrialDisclosures@gilead.com
Publications of Results:
Zhdanov K., Morozov V., Orlova-Morozova E.A., Salupere R., Kozhevnikova G., et al. Preliminary Results of an Evaluation of Ledipasvir/Sofosbuvir in Treatment-Naive Patients with Chronic HCV or HCV/HIV Co-Infection and Retreatment of Sofosbuvir-treated Patients. 8th International Conference of the White Nights of Hepatology. Saint Petersburg, Russia. June 2-3, 2016. Oral presentation.
Layout table for additonal information
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02472886     History of Changes
Other Study ID Numbers: GS-US-337-1463
2015-000690-13 ( EudraCT Number )
First Submitted: June 12, 2015
First Posted: June 16, 2015
Results First Submitted: March 30, 2017
Results First Posted: May 10, 2017
Last Update Posted: November 16, 2018