Trial Outcomes & Findings for 12 Weeks of Ledipasvir (LDV)/Sofosbuvir (SOF) With Weight-based Ribavirin vs. 24 Weeks of LDV/SOF (NCT NCT02605304)

NCT ID: NCT02605304

Last Updated: 2018-05-02

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 7 participants
• Primary outcome timeframe: 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).
• Results posted on: 2018-05-02

Participant Flow

Participants were enrolled from February to June 2016 at 3 U.S. sites.

Participant milestones

Measure	Arm A: LDV/SOF + RBV Ledipasvir/sofosbuvir + ribavirin for 12 weeks, followed by 24 weeks of post-treatment follow-up.	Arm B: LDV/SOF Ledipasvir/sofosbuvir for 24 weeks, followed by 24 weeks of post-treatment follow-up.
Overall Study STARTED	4	3
Overall Study COMPLETED	4	3
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Arm A: LDV/SOF + RBV n=4 Participants Ledipasvir/sofosbuvir + ribavirin for 12 weeks, followed by 24 weeks of post-treatment follow-up.	Arm B: LDV/SOF n=3 Participants Ledipasvir/sofosbuvir for 24 weeks, followed by 24 weeks of post-treatment follow-up.	Total n=7 Participants Total of all reporting groups
Age, Continuous	52 years n=5 Participants	58 years n=7 Participants	53 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Intravenous drug use history Never	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Intravenous drug use history Previously	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Prior hepatitis C virus (HCV) treatment regimen SOF/RBV	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Prior hepatitis C virus (HCV) treatment regimen SOF/RBV/PEG-IFN	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Cirrhosis status Cirrhotic	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Cirrhosis status Non-cirrhotic	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
HCV genotype 1A	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
HCV genotype 1B	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
HCV RNA	6.31 log10 IU/mL n=5 Participants	7.01 log10 IU/mL n=7 Participants	6.71 log10 IU/mL n=5 Participants
HIV antiretroviral treatment (ART) status On ART	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
HIV antiretroviral treatment (ART) status Not on ART	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
HIV-1 RNA quantitation Unquantifiable	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
HIV-1 RNA quantitation Quantifiable	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
CD4+ T-cell count	564 cells/mm^3 n=5 Participants	387 cells/mm^3 n=7 Participants	528 cells/mm^3 n=5 Participants

PRIMARY outcome

Timeframe: 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).

Population: All participants enrolled.

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.

Outcome measures

Measure	Arm A: LDV/SOF + RBV n=4 Participants Ledipasvir/sofosbuvir + ribavirin for 12 weeks, followed by 24 weeks of post-treatment follow-up.	Arm B: LDV/SOF n=3 Participants Ledipasvir/sofosbuvir for 24 weeks, followed by 24 weeks of post-treatment follow-up.
Percentage of Participants With Sustained Virologic Response at 12 Weeks After Treatment Discontinuation (SVR12)	100.0 percentage of participants Interval 59.7 to 100.0	100.0 percentage of participants Interval 52.6 to 100.0

PRIMARY outcome

Timeframe: 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.

Population: All participants enrolled.

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.

Outcome measures

Measure	Arm A: LDV/SOF + RBV n=4 Participants Ledipasvir/sofosbuvir + ribavirin for 12 weeks, followed by 24 weeks of post-treatment follow-up.	Arm B: LDV/SOF n=3 Participants Ledipasvir/sofosbuvir for 24 weeks, followed by 24 weeks of post-treatment follow-up.
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 Overall (any event)	50.0 percentage of participants	0 percentage of participants
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 Diagnosis ≥ Grade 3	0 percentage of participants	0 percentage of participants
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 Laboratory event ≥ Grade 3	50.0 percentage of participants	0 percentage of participants
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 Sign/symptom ≥ Grade 3	0 percentage of participants	0 percentage of participants
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 SAE	0 percentage of participants	0 percentage of participants
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 AE that led to treatment discontinuation	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: From study entry to study completion (Week 36 in Arm A, Week 48 in Arm B)

Population: All participants enrolled.

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.

Outcome measures

Measure	Arm A: LDV/SOF + RBV n=4 Participants Ledipasvir/sofosbuvir + ribavirin for 12 weeks, followed by 24 weeks of post-treatment follow-up.	Arm B: LDV/SOF n=3 Participants Ledipasvir/sofosbuvir for 24 weeks, followed by 24 weeks of post-treatment follow-up.
Percentage of Participants With Protocol-specified Renal Events Overall (any renal event)	25.0 percentage of participants	33.3 percentage of participants
Percentage of Participants With Protocol-specified Renal Events CRCL ≥ Grade 2	25.0 percentage of participants	33.3 percentage of participants
Percentage of Participants With Protocol-specified Renal Events Proteinuria	25.0 percentage of participants	0 percentage of participants
Percentage of Participants With Protocol-specified Renal Events Glucosuria	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: 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).

Population: All participants enrolled.

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.

Outcome measures

Measure	Arm A: LDV/SOF + RBV n=4 Participants Ledipasvir/sofosbuvir + ribavirin for 12 weeks, followed by 24 weeks of post-treatment follow-up.	Arm B: LDV/SOF n=3 Participants Ledipasvir/sofosbuvir for 24 weeks, followed by 24 weeks of post-treatment follow-up.
Percentage of Participants With Sustained Virologic Response at 4 Weeks After Treatment Discontinuation (SVR4)	100.0 percentage of participants Interval 59.7 to 100.0	100.0 percentage of participants Interval 52.6 to 100.0

SECONDARY outcome

Timeframe: 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).

Population: All participants enrolled.

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.

Outcome measures

Measure	Arm A: LDV/SOF + RBV n=4 Participants Ledipasvir/sofosbuvir + ribavirin for 12 weeks, followed by 24 weeks of post-treatment follow-up.	Arm B: LDV/SOF n=3 Participants Ledipasvir/sofosbuvir for 24 weeks, followed by 24 weeks of post-treatment follow-up.
Percentage of Participants With Sustained Virologic Response at 24 Weeks After Treatment Discontinuation (SVR24)	100.0 percentage of participants Interval 59.7 to 100.0	100.0 percentage of participants Interval 52.6 to 100.0

SECONDARY outcome

Timeframe: Entry (Week 0); at 1, 4, 8, 12 (and 16, 20, 24 in Arm B) weeks after study entry

Population: All participants enrolled who had HCV RNA results available at the visit.

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).

Outcome measures

Measure	Arm A: LDV/SOF + RBV n=4 Participants Ledipasvir/sofosbuvir + ribavirin for 12 weeks, followed by 24 weeks of post-treatment follow-up.	Arm B: LDV/SOF n=3 Participants Ledipasvir/sofosbuvir for 24 weeks, followed by 24 weeks of post-treatment follow-up.
Number of Participants With Unquantifiable HCV RNA Week 0: unquantifiable HCV RNA	0 Participants	0 Participants
Number of Participants With Unquantifiable HCV RNA Week 1: unquantifiable HCV RNA	1 Participants	0 Participants
Number of Participants With Unquantifiable HCV RNA Week 4: unquantifiable HCV RNA	4 Participants	3 Participants
Number of Participants With Unquantifiable HCV RNA Week 8: unquantifiable HCV RNA	4 Participants	3 Participants
Number of Participants With Unquantifiable HCV RNA Week 12: unquantifiable HCV RNA	4 Participants	2 Participants
Number of Participants With Unquantifiable HCV RNA Week 16: unquantifiable HCV RNA	—	3 Participants
Number of Participants With Unquantifiable HCV RNA Week 20: unquantifiable HCV RNA	—	3 Participants
Number of Participants With Unquantifiable HCV RNA Week 24: unquantifiable HCV RNA	—	3 Participants

SECONDARY outcome

Timeframe: Entry (Week 0); at 4, 12 (and 24 in Arm B) weeks after study entry, and at 4 weeks after treatment discontinuation

Population: All participants enrolled with HIV-1 RNA results available at the visit.

HIV-1 RNA testing was performed at a central laboratory using Abbott RealTime HIV-1 assay (Abbott Laboratories, Lake Bluff, IL, USA).

Outcome measures

Measure	Arm A: LDV/SOF + RBV n=4 Participants Ledipasvir/sofosbuvir + ribavirin for 12 weeks, followed by 24 weeks of post-treatment follow-up.	Arm B: LDV/SOF n=3 Participants Ledipasvir/sofosbuvir for 24 weeks, followed by 24 weeks of post-treatment follow-up.
Number of Participants With HIV-1 RNA >50 Copies/mL Week 0: HIV-1 RNA >50 copies/mL	0 Participants	0 Participants
Number of Participants With HIV-1 RNA >50 Copies/mL Week 4: HIV-1 RNA >50 copies/mL	0 Participants	0 Participants
Number of Participants With HIV-1 RNA >50 Copies/mL Week 12: HIV-1 RNA >50 copies/mL	0 Participants	0 Participants
Number of Participants With HIV-1 RNA >50 Copies/mL Week 24: HIV-1 RNA >50 copies/mL	—	0 Participants
Number of Participants With HIV-1 RNA >50 Copies/mL Post treatment Week 4: HIV-1 RNA >50 copies/mL	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Entry and at 12 (and 24 in Arm B) weeks after study entry

Population: All participants enrolled with CD4 result available at entry and at the post-entry visit.

Change in CD4 count was calculated as value at the post entry visit minus the value at study entry.

Outcome measures

Measure	Arm A: LDV/SOF + RBV n=4 Participants Ledipasvir/sofosbuvir + ribavirin for 12 weeks, followed by 24 weeks of post-treatment follow-up.	Arm B: LDV/SOF n=3 Participants Ledipasvir/sofosbuvir for 24 weeks, followed by 24 weeks of post-treatment follow-up.
CD4+ T-cell (CD4) Count Change From Baseline Week 12: CD4 change	-102 cells/mm^3 Interval -106.0 to -28.0	365 cells/mm^3 Interval 196.0 to 533.0
CD4+ T-cell (CD4) Count Change From Baseline Week 24: CD4 change	—	138 cells/mm^3 Interval 97.0 to 302.0

Adverse Events

Arm A: LDV/SOF + RBV

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Arm B: LDV/SOF

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Arm A: LDV/SOF + RBV n=4 participants at risk Ledipasvir/sofosbuvir + ribavirin for 12 weeks, followed by 24 weeks of post-treatment follow-up.	Arm B: LDV/SOF n=3 participants at risk Ledipasvir/sofosbuvir for 24 weeks, followed by 24 weeks of post-treatment follow-up.
Investigations Alanine aminotransferase increased	0.00% 0/4 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.	33.3% 1/3 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.
Investigations Aspartate aminotransferase increased	25.0% 1/4 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.	33.3% 1/3 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.
Investigations Bilirubin conjugated increased	25.0% 1/4 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.	33.3% 1/3 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.
Investigations Blood albumin decreased	25.0% 1/4 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.	0.00% 0/3 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.
Investigations Blood alkaline phosphatase abnormal	25.0% 1/4 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.	0.00% 0/3 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.
Investigations Blood bilirubin increased	25.0% 1/4 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.	33.3% 1/3 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.
Investigations Blood cholesterol increased	0.00% 0/4 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.	33.3% 1/3 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.
Investigations Blood creatinine increased	0.00% 0/4 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.	33.3% 1/3 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.
Investigations Blood glucose increased	0.00% 0/4 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.	33.3% 1/3 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.
Investigations Blood sodium decreased	0.00% 0/4 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.	33.3% 1/3 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.
Investigations Platelet count decreased	0.00% 0/4 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.	33.3% 1/3 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.
Renal and urinary disorders Chronic kidney disease	25.0% 1/4 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.	0.00% 0/3 • From study treatment dispensation to study completion (Week 36 in Arm A, Week 48 in Arm B). 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.

Additional Information

ACTG Clinicaltrials.gov Coordinator

ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

Phone: (301) 628-3313

Email: ACTGCT.Gov@s-3.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER