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Trial record 49 of 115 for:    "Viral Infectious Disease" | "Ledipasvir"

12 Weeks of Ledipasvir (LDV)/Sofosbuvir (SOF) With Weight-based Ribavirin vs. 24 Weeks of LDV/SOF

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ClinicalTrials.gov Identifier: NCT02605304
Recruitment Status : Terminated (The study experienced enrollment difficulties.)
First Posted : November 16, 2015
Results First Posted : February 15, 2018
Last Update Posted : May 2, 2018
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
AIDS Clinical Trials Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions HIV-1 Infection
Hepatitis C
Interventions Drug: Ledipasvir/sofosbuvir
Drug: Ribavirin
Enrollment 7
Recruitment Details Participants were enrolled from February to June 2016 at 3 U.S. sites.
Pre-assignment Details  
Arm/Group Title Arm A: LDV/SOF + RBV Arm B: LDV/SOF
Hide Arm/Group Description Ledipasvir/sofosbuvir + ribavirin for 12 weeks, followed by 24 weeks of post-treatment follow-up. Ledipasvir/sofosbuvir for 24 weeks, followed by 24 weeks of post-treatment follow-up.
Period Title: Overall Study
Started 4 3
Completed 4 3
Not Completed 0 0
Arm/Group Title Arm A: LDV/SOF + RBV Arm B: LDV/SOF Total
Hide Arm/Group Description Ledipasvir/sofosbuvir + ribavirin for 12 weeks, followed by 24 weeks of post-treatment follow-up. Ledipasvir/sofosbuvir for 24 weeks, followed by 24 weeks of post-treatment follow-up. Total of all reporting groups
Overall Number of Baseline Participants 4 3 7
Hide Baseline Analysis Population Description
All participants enrolled.
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 4 participants 3 participants 7 participants
52
(49 to 57)
58
(49 to 65)
53
(49 to 61)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 3 participants 7 participants
Female
0
   0.0%
2
  66.7%
2
  28.6%
Male
4
 100.0%
1
  33.3%
5
  71.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 3 participants 7 participants
Hispanic or Latino
2
  50.0%
1
  33.3%
3
  42.9%
Not Hispanic or Latino
2
  50.0%
2
  66.7%
4
  57.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 3 participants 7 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
  25.0%
2
  66.7%
3
  42.9%
White
3
  75.0%
1
  33.3%
4
  57.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 4 participants 3 participants 7 participants
4
 100.0%
3
 100.0%
7
 100.0%
Intravenous drug use history  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 3 participants 7 participants
Never
2
  50.0%
3
 100.0%
5
  71.4%
Previously
2
  50.0%
0
   0.0%
2
  28.6%
Prior hepatitis C virus (HCV) treatment regimen  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 3 participants 7 participants
SOF/RBV
2
  50.0%
1
  33.3%
3
  42.9%
SOF/RBV/PEG-IFN
2
  50.0%
2
  66.7%
4
  57.1%
Cirrhosis status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 3 participants 7 participants
Cirrhotic
1
  25.0%
0
   0.0%
1
  14.3%
Non-cirrhotic
3
  75.0%
3
 100.0%
6
  85.7%
[1]
Measure Description: Cirrhotic was defined as: liver biopsy showing cirrhosis (Metavir score =4, Ishak score ≥5 or equivalent) at any time prior to study entry; or transient elastography (FibroScan®; Echosens, Paris, France) ≥12.5 kPa within 12 months of study entry; or HCV FibroSURE® (Laboratory Corporation of America, Raritan, NJ, USA) score of ≥0.72 with aspartate aminotransferase:platelet ratio index (APRI) ≥2 within 12 months of study entry.
HCV genotype  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 3 participants 7 participants
1A
2
  50.0%
3
 100.0%
5
  71.4%
1B
2
  50.0%
0
   0.0%
2
  28.6%
HCV RNA   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Log10 IU/mL
Number Analyzed 4 participants 3 participants 7 participants
6.31
(5.80 to 6.66)
7.01
(6.73 to 7.48)
6.71
(6.00 to 7.01)
[1]
Measure Description: HCV RNA testing was performed at a central laboratory using the COBAS® AmpliPrep/COBAS® TaqMan® HCV Quantitative Test, version 2.0 (Roche Diagnostics, Rotkreuz, Switzerland).
HIV antiretroviral treatment (ART) status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 3 participants 7 participants
On ART
4
 100.0%
3
 100.0%
7
 100.0%
Not on ART
0
   0.0%
0
   0.0%
0
   0.0%
HIV-1 RNA quantitation   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 3 participants 7 participants
Unquantifiable
4
 100.0%
3
 100.0%
7
 100.0%
Quantifiable
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Description: HIV-1 RNA testing was performed at a central laboratory using Abbott RealTime HIV-1 assay (Abbott Laboratories, Lake Bluff, IL, USA). Unquantifiable was defined as below the lower limit of quantitation (LLOQ) of the assay (40 copies/mL).
CD4+ T-cell count  
Median (Inter-Quartile Range)
Unit of measure:  Cells/mm^3
Number Analyzed 4 participants 3 participants 7 participants
564
(435 to 614)
387
(200 to 1150)
528
(341 to 628)
1.Primary Outcome
Title Percentage of Participants With Sustained Virologic Response at 12 Weeks After Treatment Discontinuation (SVR12)
Hide Description SVR12 was defined as HCV RNA below the LLOQ of the assay (either target detected [TD] or target not detected [TND]) at 12 weeks after treatment discontinuation. The sample within the visit window, closest to the targeted time was used. If there was no HCV RNA sample within visit window, then the participant was considered not to have achieved SVR12, unless there were preceding and subsequent HCV RNA measurements that were both <LLOQ (either TD or TND). HCV RNA testing was conducted at a central laboratory using the COBAS® AmpliPrep/COBAS® TaqMan® HCV Quantitative Test, version 2.0 (Roche Diagnostics, Rotkreuz, Switzerland). Wilson (score) method was used for confidence intervals.
Time Frame At 12 weeks after treatment discontinuation (i.e., at 24 weeks after study entry in Arm A and at 36 weeks after study entry in Arm B).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants enrolled.
Arm/Group Title Arm A: LDV/SOF + RBV Arm B: LDV/SOF
Hide Arm/Group Description:
Ledipasvir/sofosbuvir + ribavirin for 12 weeks, followed by 24 weeks of post-treatment follow-up.
Ledipasvir/sofosbuvir for 24 weeks, followed by 24 weeks of post-treatment follow-up.
Overall Number of Participants Analyzed 4 3
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
100.0
(59.7 to 100.0)
100.0
(52.6 to 100.0)
2.Primary Outcome
Title Percentage of Participants With Grade 3 or Higher Adverse Event (AE), Serious AE (SAE), or AE Reported as the Reason for Permanent Discontinuation of Study Treatment
Hide Description Percentage of participants who experienced an AE (diagnosis, sign/symptom or laboratory abnormality) of ≥Grade 3, SAE according to International Conference on Harmonisation (ICH) criteria, or AE reported as the reason for permanent study treatment discontinuation, during study treatment and up to 30 days after study treatment. Events that were ongoing at the same grade from prior to study treatment initiation were excluded. AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (V2.0) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening. The percentage of participants who experienced any event (overall), and the percentage of participants who experienced each component of the outcome are provided in the data table below. The categories are not mutually exclusive. A participant may have experienced multiple events. Each participant is counted at most once within category, and in the overall summary line.
Time Frame From study treatment initiation to 30 days after study treatment discontinuation. Duration of treatment was 12 weeks in Arm A and 24 weeks in Arm B.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants enrolled.
Arm/Group Title Arm A: LDV/SOF + RBV Arm B: LDV/SOF
Hide Arm/Group Description:
Ledipasvir/sofosbuvir + ribavirin for 12 weeks, followed by 24 weeks of post-treatment follow-up.
Ledipasvir/sofosbuvir for 24 weeks, followed by 24 weeks of post-treatment follow-up.
Overall Number of Participants Analyzed 4 3
Measure Type: Number
Unit of Measure: percentage of participants
Overall (any event) 50.0 0
Diagnosis ≥ Grade 3 0 0
Laboratory event ≥ Grade 3 50.0 0
Sign/symptom ≥ Grade 3 0 0
SAE 0 0
AE that led to treatment discontinuation 0 0
3.Secondary Outcome
Title Percentage of Participants With Protocol-specified Renal Events
Hide Description The study protocol defined renal events as (1) ≥Grade 2 creatinine clearance (CRCL) after study entry, or (2) new urinalysis proteinuria and/or glucosuria, defined as ≥1+ or an increase ≥1+ from baseline. The percentage of participants who experienced any renal event, and the percentages of participants who experienced each component of the outcome are provided in the data table below. The categories are not mutually exclusive. A participant may have experienced multiple events. Each participant is counted at most once within category, and in the overall summary line.
Time Frame From study entry to study completion (Week 36 in Arm A, Week 48 in Arm B)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants enrolled.
Arm/Group Title Arm A: LDV/SOF + RBV Arm B: LDV/SOF
Hide Arm/Group Description:
Ledipasvir/sofosbuvir + ribavirin for 12 weeks, followed by 24 weeks of post-treatment follow-up.
Ledipasvir/sofosbuvir for 24 weeks, followed by 24 weeks of post-treatment follow-up.
Overall Number of Participants Analyzed 4 3
Measure Type: Number
Unit of Measure: percentage of participants
Overall (any renal event) 25.0 33.3
CRCL ≥ Grade 2 25.0 33.3
Proteinuria 25.0 0
Glucosuria 0 0
4.Secondary Outcome
Title Percentage of Participants With Sustained Virologic Response at 4 Weeks After Treatment Discontinuation (SVR4)
Hide Description SVR4 was defined as HCV RNA below the LLOQ of the assay (either TD or TND) at 4 weeks after treatment discontinuation. The sample within the visit window, closest to the targeted time was used. If there was no HCV RNA sample within visit window, then the participant was considered not to have achieved SVR4, unless there were preceding and subsequent HCV RNA measurements that were both <LLOQ (either TD or TND). HCV RNA testing was conducted at a central laboratory using the COBAS® AmpliPrep/COBAS® TaqMan® HCV Quantitative Test, version 2.0 (Roche Diagnostics, Rotkreuz, Switzerland). Wilson (score) method was used for confidence intervals.
Time Frame At 4 weeks after treatment discontinuation (i.e., at 16 weeks after study entry in Arm A and at 28 weeks after study entry in Arm B).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants enrolled.
Arm/Group Title Arm A: LDV/SOF + RBV Arm B: LDV/SOF
Hide Arm/Group Description:
Ledipasvir/sofosbuvir + ribavirin for 12 weeks, followed by 24 weeks of post-treatment follow-up.
Ledipasvir/sofosbuvir for 24 weeks, followed by 24 weeks of post-treatment follow-up.
Overall Number of Participants Analyzed 4 3
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
100.0
(59.7 to 100.0)
100.0
(52.6 to 100.0)
5.Secondary Outcome
Title Percentage of Participants With Sustained Virologic Response at 24 Weeks After Treatment Discontinuation (SVR24)
Hide Description SVR24 was defined as HCV RNA below the LLOQ of the assay (either TD or TND) at 24 weeks after treatment discontinuation. The sample from a visit greater than 20 weeks after treatment discontinuation which was closest to the targeted week (24 weeks post treatment), not followed by any HCV RNA result ≥LLOQ, was used. If there was no HCV RNA sample within this window, then the participant was considered not to have achieved SVR24. HCV RNA testing was conducted at a central laboratory using the COBAS® AmpliPrep/COBAS® TaqMan® HCV Quantitative Test, version 2.0 (Roche Diagnostics, Rotkreuz, Switzerland). Wilson (score) method was used for confidence intervals.
Time Frame At 24 weeks after treatment discontinuation (i.e., at 36 weeks after study entry in Arm A and at 48 weeks after study entry in Arm B).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants enrolled.
Arm/Group Title Arm A: LDV/SOF + RBV Arm B: LDV/SOF
Hide Arm/Group Description:
Ledipasvir/sofosbuvir + ribavirin for 12 weeks, followed by 24 weeks of post-treatment follow-up.
Ledipasvir/sofosbuvir for 24 weeks, followed by 24 weeks of post-treatment follow-up.
Overall Number of Participants Analyzed 4 3
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
100.0
(59.7 to 100.0)
100.0
(52.6 to 100.0)
6.Secondary Outcome
Title Number of Participants With Unquantifiable HCV RNA
Hide Description Unquantifiable HCV was defined as HCV RNA below the LLOQ of the assay (15 IU/mL), either TD or TND. HCV RNA testing was conducted at a central laboratory using the COBAS® AmpliPrep/COBAS® TaqMan® HCV Quantitative Test, version 2.0 (Roche Diagnostics, Rotkreuz, Switzerland).
Time Frame Entry (Week 0); at 1, 4, 8, 12 (and 16, 20, 24 in Arm B) weeks after study entry
Hide Outcome Measure Data
Hide Analysis Population Description
All participants enrolled who had HCV RNA results available at the visit.
Arm/Group Title Arm A: LDV/SOF + RBV Arm B: LDV/SOF
Hide Arm/Group Description:
Ledipasvir/sofosbuvir + ribavirin for 12 weeks, followed by 24 weeks of post-treatment follow-up.
Ledipasvir/sofosbuvir for 24 weeks, followed by 24 weeks of post-treatment follow-up.
Overall Number of Participants Analyzed 4 3
Measure Type: Count of Participants
Unit of Measure: Participants
Week 0: unquantifiable HCV RNA Number Analyzed 4 participants 3 participants
0
   0.0%
0
   0.0%
Week 1: unquantifiable HCV RNA Number Analyzed 4 participants 3 participants
1
  25.0%
0
   0.0%
Week 4: unquantifiable HCV RNA Number Analyzed 4 participants 3 participants
4
 100.0%
3
 100.0%
Week 8: unquantifiable HCV RNA Number Analyzed 4 participants 3 participants
4
 100.0%
3
 100.0%
Week 12: unquantifiable HCV RNA Number Analyzed 4 participants 2 participants
4
 100.0%
2
 100.0%
Week 16: unquantifiable HCV RNA Number Analyzed 0 participants 3 participants
3
 100.0%
Week 20: unquantifiable HCV RNA Number Analyzed 0 participants 3 participants
3
 100.0%
Week 24: unquantifiable HCV RNA Number Analyzed 0 participants 3 participants
3
 100.0%
7.Secondary Outcome
Title Number of Participants With HIV-1 RNA >50 Copies/mL
Hide Description HIV-1 RNA testing was performed at a central laboratory using Abbott RealTime HIV-1 assay (Abbott Laboratories, Lake Bluff, IL, USA).
Time Frame Entry (Week 0); at 4, 12 (and 24 in Arm B) weeks after study entry, and at 4 weeks after treatment discontinuation
Hide Outcome Measure Data
Hide Analysis Population Description
All participants enrolled with HIV-1 RNA results available at the visit.
Arm/Group Title Arm A: LDV/SOF + RBV Arm B: LDV/SOF
Hide Arm/Group Description:
Ledipasvir/sofosbuvir + ribavirin for 12 weeks, followed by 24 weeks of post-treatment follow-up.
Ledipasvir/sofosbuvir for 24 weeks, followed by 24 weeks of post-treatment follow-up.
Overall Number of Participants Analyzed 4 3
Measure Type: Count of Participants
Unit of Measure: Participants
Week 0: HIV-1 RNA >50 copies/mL Number Analyzed 4 participants 3 participants
0
   0.0%
0
   0.0%
Week 4: HIV-1 RNA >50 copies/mL Number Analyzed 4 participants 3 participants
0
   0.0%
0
   0.0%
Week 12: HIV-1 RNA >50 copies/mL Number Analyzed 4 participants 2 participants
0
   0.0%
0
   0.0%
Week 24: HIV-1 RNA >50 copies/mL Number Analyzed 0 participants 3 participants
0
   0.0%
Post treatment Week 4: HIV-1 RNA >50 copies/mL Number Analyzed 4 participants 2 participants
0
   0.0%
0
   0.0%
8.Secondary Outcome
Title CD4+ T-cell (CD4) Count Change From Baseline
Hide Description Change in CD4 count was calculated as value at the post entry visit minus the value at study entry.
Time Frame Entry and at 12 (and 24 in Arm B) weeks after study entry
Hide Outcome Measure Data
Hide Analysis Population Description
All participants enrolled with CD4 result available at entry and at the post-entry visit.
Arm/Group Title Arm A: LDV/SOF + RBV Arm B: LDV/SOF
Hide Arm/Group Description:
Ledipasvir/sofosbuvir + ribavirin for 12 weeks, followed by 24 weeks of post-treatment follow-up.
Ledipasvir/sofosbuvir for 24 weeks, followed by 24 weeks of post-treatment follow-up.
Overall Number of Participants Analyzed 4 3
Median (Inter-Quartile Range)
Unit of Measure: cells/mm^3
Week 12: CD4 change Number Analyzed 3 participants 2 participants
-102
(-106 to -28)
365
(196 to 533)
Week 24: CD4 change Number Analyzed 0 participants 3 participants
138
(97 to 302)
Time Frame From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B).
Adverse Event Reporting Description At entry, all diagnoses, signs/symptoms and laboratory values were collected, regardless of grade. Post-entry, diagnoses, signs/symptoms and laboratory values of ≥Grade 3 and events that led to change in treatment (excluding indications for RBV dose modifications) or that met ICH, expedited AE, or SAE guidelines, regardless of grade, were collected. Creatinine and creatinine clearance were reported regardless of grade. The DAIDS AE Grading Table (V2.0) and Expedited AE Manual (V2.0) were used.
 
Arm/Group Title Arm A: LDV/SOF + RBV Arm B: LDV/SOF
Hide Arm/Group Description Ledipasvir/sofosbuvir + ribavirin for 12 weeks, followed by 24 weeks of post-treatment follow-up. Ledipasvir/sofosbuvir for 24 weeks, followed by 24 weeks of post-treatment follow-up.
All-Cause Mortality
Arm A: LDV/SOF + RBV Arm B: LDV/SOF
Affected / at Risk (%) Affected / at Risk (%)
Total   0/4 (0.00%)   0/3 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Arm A: LDV/SOF + RBV Arm B: LDV/SOF
Affected / at Risk (%) Affected / at Risk (%)
Total   0/4 (0.00%)   0/3 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm A: LDV/SOF + RBV Arm B: LDV/SOF
Affected / at Risk (%) Affected / at Risk (%)
Total   2/4 (50.00%)   3/3 (100.00%) 
Investigations     
Alanine aminotransferase increased  1  0/4 (0.00%)  1/3 (33.33%) 
Aspartate aminotransferase increased  1  1/4 (25.00%)  1/3 (33.33%) 
Bilirubin conjugated increased  1  1/4 (25.00%)  1/3 (33.33%) 
Blood albumin decreased  1  1/4 (25.00%)  0/3 (0.00%) 
Blood alkaline phosphatase abnormal  1  1/4 (25.00%)  0/3 (0.00%) 
Blood bilirubin increased  1  1/4 (25.00%)  1/3 (33.33%) 
Blood cholesterol increased  1  0/4 (0.00%)  1/3 (33.33%) 
Blood creatinine increased  1  0/4 (0.00%)  1/3 (33.33%) 
Blood glucose increased  1  0/4 (0.00%)  1/3 (33.33%) 
Blood sodium decreased  1  0/4 (0.00%)  1/3 (33.33%) 
Platelet count decreased  1  0/4 (0.00%)  1/3 (33.33%) 
Renal and urinary disorders     
Chronic kidney disease  1  1/4 (25.00%)  0/3 (0.00%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
The study accrual was terminated prematurely due to enrollment challenges. There was a small number of participants enrolled.
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.
In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: ACTG Clinicaltrials.gov Coordinator
Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
Phone: (301) 628-3313
EMail: ACTGCT.Gov@s-3.com
Layout table for additonal information
Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT02605304     History of Changes
Other Study ID Numbers: ACTG A5348
UM1AI068636 ( U.S. NIH Grant/Contract )
First Submitted: November 12, 2015
First Posted: November 16, 2015
Results First Submitted: January 10, 2018
Results First Posted: February 15, 2018
Last Update Posted: May 2, 2018