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Comparative Efficacy of Fixed-dose Combination Sofosbuvir + Ledipasvir, 8 vs. 12 Weeks in Chronic Hepatitis C Genotype 6

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ClinicalTrials.gov Identifier: NCT02480166
Recruitment Status : Completed
First Posted : June 24, 2015
Results First Posted : September 19, 2017
Last Update Posted : September 19, 2017
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Mindie H. Nguyen, Stanford University

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition PT-NANBH
Interventions Drug: 8 weeks SOF/LED
Drug: 12 weeks SOF/LED
Enrollment 60
Recruitment Details  
Pre-assignment Details  
Arm/Group Title 8 Weeks SOF/LED 12 Weeks SOF/LED Extended Treatment to 12 Weeks SOF/LED
Hide Arm/Group Description

Patients that are treatment naïve and without cirrhosis will be assigned to 8 weeks of treatment with fixed-dose combination sofosbuvir (400 mg) and ledipasvir (90 mg) daily.

8 weeks SOF/LED: Eligible and consenting patients will be treated with sofosbuvir 400 mg daily and ledipasvir 90 mg daily for 8 weeks. Patients that are treatment naïve and without cirrhosis will be assigned to 8 weeks of treatment. The drug will be administered orally, per manufacturers’ instructions, and can be taken with or without food.

Patients that are either treatment experienced or are cirrhotic will be assigned to 12 weeks of treatment with fixed-dose combination sofosbuvir (400 mg) and ledipasvir (90 mg) daily.

12 weeks SOF/LED: Eligible and consenting patients will be treated with sofosbuvir 400 mg daily and ledipasvir 90 mg daily for 8 weeks. Patients that are not treatment naïve or have cirrhosis will be assigned to 12 weeks of treatment. The drug will be administered orally, per manufacturers’ instructions, and can be taken with or without food.

Subjects without cirrhosis or prior treatment history received extended treatment to 12 weeks by investigator’s preference
Period Title: Overall Study
Started 20 36 4
Completed 20 36 4
Not Completed 0 0 0
Arm/Group Title 8 Weeks SOF/LED 12 Weeks SOF/LED Extended Treatment to 12 Weeks SOF/LED Total
Hide Arm/Group Description

Patients that are treatment naïve and without cirrhosis will be assigned to 8 weeks of treatment with fixed-dose combination sofosbuvir (400 mg) and ledipasvir (90 mg) daily.

8 weeks SOF/LED: Eligible and consenting patients will be treated with sofosbuvir 400 mg daily and ledipasvir 90 mg daily for 8 weeks. Patients that are treatment naïve and without cirrhosis will be assigned to 8 weeks of treatment. The drug will be administered orally, per manufacturers’ instructions, and can be taken with or without food.

Patients that are either treatment experienced or are cirrhotic will be assigned to 12 weeks of treatment with fixed-dose combination sofosbuvir (400 mg) and ledipasvir (90 mg) daily.

12 weeks SOF/LED: Eligible and consenting patients will be treated with sofosbuvir 400 mg daily and ledipasvir 90 mg daily for 8 weeks. Patients that are not treatment naïve or have cirrhosis will be assigned to 12 weeks of treatment. The drug will be administered orally, per manufacturers’ instructions, and can be taken with or without food.

Subjects without cirrhosis or prior treatment history received extended treatment to 12 weeks by investigator’s preference Total of all reporting groups
Overall Number of Baseline Participants 20 36 4 60
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 20 participants 36 participants 4 participants 60 participants
57  (8) 60  (12) 54  (10) 59  (10)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 36 participants 4 participants 60 participants
Female
9
  45.0%
15
  41.7%
1
  25.0%
25
  41.7%
Male
11
  55.0%
21
  58.3%
3
  75.0%
35
  58.3%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 36 participants 4 participants 60 participants
Vietnamese
16
  80.0%
30
  83.3%
4
 100.0%
50
  83.3%
Cambodian
1
   5.0%
3
   8.3%
0
   0.0%
4
   6.7%
Other Asian
3
  15.0%
3
   8.3%
0
   0.0%
6
  10.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 20 participants 36 participants 4 participants 60 participants
20
 100.0%
36
 100.0%
4
 100.0%
60
 100.0%
BMI  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 20 participants 36 participants 4 participants 60 participants
22.4  (4.2) 24.2  (2.7) 24.1  (3.6) 23.6  (3.3)
Comorbidities  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 36 participants 4 participants 60 participants
Diabetes
1
   5.0%
6
  16.7%
0
   0.0%
7
  11.7%
Hypertension
5
  25.0%
10
  27.8%
0
   0.0%
15
  25.0%
Hyperlipidemia
3
  15.0%
6
  16.7%
0
   0.0%
9
  15.0%
Coronary Artery Disease (CAD)
0
   0.0%
1
   2.8%
0
   0.0%
1
   1.7%
Chronic Obstructive Pulmonary Disease (COPD)
0
   0.0%
1
   2.8%
0
   0.0%
1
   1.7%
HCV Genotype SubType  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 36 participants 4 participants 60 participants
a/b
2
  10.0%
9
  25.0%
2
  50.0%
13
  21.7%
c-l
8
  40.0%
15
  41.7%
2
  50.0%
25
  41.7%
c
1
   5.0%
0
   0.0%
0
   0.0%
1
   1.7%
m
0
   0.0%
2
   5.6%
0
   0.0%
2
   3.3%
Baseline Cirrhosis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 36 participants 4 participants 60 participants
0
   0.0%
27
  75.0%
0
   0.0%
27
  45.0%
Decompensated Cirrhosis   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 36 participants 4 participants 60 participants
0
   0.0%
2
   5.6%
0
   0.0%
2
   3.3%
[1]
Measure Description: Decompensated cirrhosis is defined as presence/history of variceal bleeding, hepatic encephalopathy, or ascites at baseline.
Hepatocellular Carcinoma  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 36 participants 4 participants 60 participants
0
   0.0%
3
   8.3%
0
   0.0%
3
   5.0%
Prior Treatment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 36 participants 4 participants 60 participants
0
   0.0%
15
  41.7%
0
   0.0%
15
  25.0%
Proton Pump Inhibitor (PPI) usage  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 36 participants 4 participants 60 participants
3
  15.0%
9
  25.0%
0
   0.0%
12
  20.0%
MELD, cirrhotics only   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 20 participants 36 participants 4 participants 60 participants
0  (0) 6.9  (1.6) 0  (0) 6.9  (1.6)
[1]
Measure Description: The Model for End-Stage Liver Disease (MELD) Score uses the patient's values for serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time (INR) to predict survival. It is calculated according to the following formula: MELD = 3.78×ln[serum bilirubin (mg/dL)] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43. The total possible range for MELD scores is 6 (less ill) to 40 (gravely ill).
log10 HCV RNA  
Mean (Standard Deviation)
Unit of measure:  Log10 (IU/ml)
Number Analyzed 20 participants 36 participants 4 participants 60 participants
6.2  (0.8) 6.5  (0.6) 7.2  (0.3) 6.5  (0.7)
White Blood Cell Count (WBC)  
Mean (Standard Deviation)
Unit of measure:  K/uL
Number Analyzed 20 participants 36 participants 4 participants 60 participants
5.5  (1.4) 6.0  (2.1) 5.3  (0.5) 5.8  (1.8)
Hemoglobin  
Mean (Standard Deviation)
Unit of measure:  g/dL
Number Analyzed 20 participants 36 participants 4 participants 60 participants
14.3  (1.3) 14.2  (1.6) 14.8  (1.1) 14.2  (1.5)
Platelets  
Median (Inter-Quartile Range)
Unit of measure:  K/uL
Number Analyzed 20 participants 36 participants 4 participants 60 participants
213
(186 to 240)
181
(133 to 223)
201
(189 to 225)
201
(151 to 223)
Creatinine  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 20 participants 36 participants 4 participants 60 participants
0.8  (0.1) 0.9  (0.2) 0.9  (0.1) 0.8  (0.2)
International Normalized Ratio (INR)   [1] 
Mean (Standard Deviation)
Unit of measure:  Ratio
Number Analyzed 20 participants 36 participants 4 participants 60 participants
1.0  (0.2) 1.0  (0.1) 1.0  (0.0) 1.0  (0.1)
[1]
Measure Description: The INR is based on the ratio of the patient's prothrombin time and the normal mean prothrombin time. The normal range for a healthy person who is not on anticoagulant therapy is 0.8-1.2, while higher values are targeted for people on anticoagulant therapy.
Total bilirubin  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 20 participants 36 participants 4 participants 60 participants
0.7  (0.1) 0.8  (0.4) 0.9  (0.1) 0.7  (0.3)
Aspartate Aminotransferase (AST)   [1] 
Median (Inter-Quartile Range)
Unit of measure:  U/L
Number Analyzed 20 participants 36 participants 4 participants 60 participants
36
(27 to 44)
48
(33 to 95)
28
(21 to 34)
39
(29 to 69)
[1]
Measure Description: AST is an enzyme that is secreted from the liver and can be found in liver, heart, muscle tissue, pancreas and kidneys. Elevated levels of AST may indicate inflammation or liver damage. Normal range for AST is typically 10-40 U/L.
Alanine Aminotransferase (ALT)   [1] 
Median (Inter-Quartile Range)
Unit of measure:  U/L
Number Analyzed 20 participants 36 participants 4 participants 60 participants
44
(31 to 59)
68
(46 to 105)
33
(21 to 41)
59
(36 to 76)
[1]
Measure Description: ALT is an enzyme that is secreted by the liver into the blood. Main storage of this enzyme is in the liver and elevated levels of ALT in the blood may indicate liver inflammation or damage. Normal range for ALT is typically between 7-56 U/L.
Albumin  
Mean (Standard Deviation)
Unit of measure:  g/dL
Number Analyzed 20 participants 36 participants 4 participants 60 participants
4.3  (0.4) 4.0  (0.7) 3.5  (1.5) 4.0  (0.7)
1.Primary Outcome
Title Number of Participants With a Sustained Virologic Response (SVR) log10 HCV RNA PCR <25 IU/mL 12 Weeks Post-treatment
Hide Description [Not Specified]
Time Frame 12 weeks after end of therapy
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 8 Weeks SOF/LED 12 Weeks SOF/LED Treatment Extension to 12 Weeks SOF/LED
Hide Arm/Group Description:

Patients that are treatment naïve and without cirrhosis will be assigned to 8 weeks of treatment with fixed-dose combination sofosbuvir (400 mg) and ledipasvir (90 mg) daily.

8 weeks SOF/LED: Eligible and consenting patients will be treated with sofosbuvir 400 mg daily and ledipasvir 90 mg daily for 8 weeks. Patients that are treatment naïve and without cirrhosis will be assigned to 8 weeks of treatment. The drug will be administered orally, per manufacturers’ instructions, and can be taken with or without food.

Patients that are either treatment experienced or are cirrhotic will be assigned to 12 weeks of treatment with fixed-dose combination sofosbuvir (400 mg) and ledipasvir (90 mg) daily.

12 weeks SOF/LED: Eligible and consenting patients will be treated with sofosbuvir 400 mg daily and ledipasvir 90 mg daily for 8 weeks. Patients that are not treatment naïve or have cirrhosis will be assigned to 12 weeks of treatment. The drug will be administered orally, per manufacturers’ instructions, and can be taken with or without food.

Subjects without cirrhosis or prior treatment history received extended treatment to 12 weeks by investigator’s preference
Overall Number of Participants Analyzed 20 36 4
Measure Type: Count of Participants
Unit of Measure: Participants
19
  95.0%
34
  94.4%
4
 100.0%
2.Secondary Outcome
Title Number of Participants Who Experienced Serious Adverse Events (SAEs) and/or Adverse Events (AEs) From Informed Consent to 12 Weeks Post-treatment.
Hide Description Adverse events were defined using Common Terminology Criteria for Adverse Events v3.0 (CTCAE)
Time Frame Day 1 of treatment to 12 weeks post treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 8 Weeks SOF/LED 12 Weeks SOF/LED Extended Treatment to 12 Weeks SOF/LED
Hide Arm/Group Description:

Patients that are treatment naïve and without cirrhosis will be assigned to 8 weeks of treatment with fixed-dose combination sofosbuvir (400 mg) and ledipasvir (90 mg) daily.

8 weeks SOF/LED: Eligible and consenting patients will be treated with sofosbuvir 400 mg daily and ledipasvir 90 mg daily for 8 weeks. Patients that are treatment naïve and without cirrhosis will be assigned to 8 weeks of treatment. The drug will be administered orally, per manufacturers’ instructions, and can be taken with or without food.

Patients that are either treatment experienced or are cirrhotic will be assigned to 12 weeks of treatment with fixed-dose combination sofosbuvir (400 mg) and ledipasvir (90 mg) daily.

12 weeks SOF/LED: Eligible and consenting patients will be treated with sofosbuvir 400 mg daily and ledipasvir 90 mg daily for 8 weeks. Patients that are not treatment naïve or have cirrhosis will be assigned to 12 weeks of treatment. The drug will be administered orally, per manufacturers’ instructions, and can be taken with or without food.

Subjects without cirrhosis or prior treatment history received extended treatment to 12 weeks by investigator’s preference
Overall Number of Participants Analyzed 20 36 4
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
Time Frame For each subject, AEs and SAEs are recorded after informed consent is obtained until 12 weeks post treatment.
Adverse Event Reporting Description

A Serious Adverse event must be reported if it occurs during a subject’s participation in the Study (whether receiving Study Product or not) and within 30 days of receiving the last dose of Study Product.

Any serious adverse event that is ongoing when a subject completes his/her participation in the Study must be followed until the event resolves or stabilizes, returns baseline condition, or can be attributed to agents(s) other than the Study Product, or unrelated to Study conduct.

 
Arm/Group Title 8 Weeks SOF/LED 12 Weeks SOF/LED Extended Treatment to 12 Weeks SOF/LED
Hide Arm/Group Description

Patients that are treatment naïve and without cirrhosis will be assigned to 8 weeks of treatment with fixed-dose combination sofosbuvir (400 mg) and ledipasvir (90 mg) daily.

8 weeks SOF/LED: Eligible and consenting patients will be treated with sofosbuvir 400 mg daily and ledipasvir 90 mg daily for 8 weeks. Patients that are treatment naïve and without cirrhosis will be assigned to 8 weeks of treatment. The drug will be administered orally, per manufacturers’ instructions, and can be taken with or without food.

Patients that are either treatment experienced or are cirrhotic will be assigned to 12 weeks of treatment with fixed-dose combination sofosbuvir (400 mg) and ledipasvir (90 mg) daily.

12 weeks SOF/LED: Eligible and consenting patients will be treated with sofosbuvir 400 mg daily and ledipasvir 90 mg daily for 8 weeks. Patients that are not treatment naïve or have cirrhosis will be assigned to 12 weeks of treatment. The drug will be administered orally, per manufacturers’ instructions, and can be taken with or without food.

Subjects without cirrhosis or prior treatment history received extended treatment to 12 weeks by investigator’s preference
All-Cause Mortality
8 Weeks SOF/LED 12 Weeks SOF/LED Extended Treatment to 12 Weeks SOF/LED
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/20 (0.00%)      0/36 (0.00%)      0/4 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
8 Weeks SOF/LED 12 Weeks SOF/LED Extended Treatment to 12 Weeks SOF/LED
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/20 (0.00%)      2/36 (5.56%)      0/4 (0.00%)    
Gastrointestinal disorders       
Upper GI Bleed  [1]  0/20 (0.00%)  0 1/36 (2.78%)  1 0/4 (0.00%)  0
Surgical and medical procedures       
Surgical correction of left wrist fracture  [2]  0/20 (0.00%)  0 1/36 (2.78%)  1 0/4 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
H.pylori-related bleeding gastric ulcer unrelated to study treatment. Subject achieved SVR 12.
[2]
Surgical correction for wrist fracture due to a mechanical fall unrelated to study treatment. Subject achieved SVR 12.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
8 Weeks SOF/LED 12 Weeks SOF/LED Extended Treatment to 12 Weeks SOF/LED
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/20 (10.00%)      5/36 (13.89%)      0/4 (0.00%)    
General disorders       
Fatigue  [1]  2/20 (10.00%)  2 1/36 (2.78%)  1 0/4 (0.00%)  0
Insomnia   0/20 (0.00%)  0 2/36 (5.56%)  2 0/4 (0.00%)  0
Nausea   0/20 (0.00%)  0 1/36 (2.78%)  1 0/4 (0.00%)  0
Headache   0/20 (0.00%)  0 1/36 (2.78%)  1 0/4 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
Fatigue
Our population was small and our study was not powered to be able to determine significant differences between groups.
Certain Agreements
Principal Investigators are NOT 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.
Results Point of Contact
Name/Title: Mindie H. Nguyen, MD, MAS
Organization: Stanford University Medical Center
Phone: 650-4985691
Publications:
Responsible Party: Mindie H. Nguyen, Stanford University
ClinicalTrials.gov Identifier: NCT02480166     History of Changes
Other Study ID Numbers: 33196
First Submitted: June 17, 2015
First Posted: June 24, 2015
Results First Submitted: July 17, 2017
Results First Posted: September 19, 2017
Last Update Posted: September 19, 2017