A Phase 3, Open-label Study to Investigate the Efficacy and Safety of Sofosbuvir Plus Ribavirin in Chronic Genotype 1, 2, 3 and 4 Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) Co-infected Adults

A Phase 3, Open-label Study to Investigate the Efficacy and Safety of Sofosbuvir Plus Ribavirin in Chronic Genotype 1, 2, 3 and 4 Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) Co-infected Subjects

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01783678

Enrollment

275

Registered

2013-02-05

Start date

2013-01-31

Completion date

2014-07-31

Last updated

2015-04-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Hepatitis C, Human Immunodeficiency Virus

Brief summary

This is an Open-label Phase 3 study in adults with chronic genotypes 1, 2, 3, and 4 HCV infection who are co-infected with HIV-1.

Interventions

DRUGRBV

Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (\< 75kg = 1000 mg and ≥ 75 kg = 1200 mg)

DRUGSofosbuvir

Sofosbuvir 400 mg tablet administered orally once daily

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Age ≥ 18 years with HIV-1 and chronic HCV genotype 1, 2, 3, or 4 co-infection * HCV RNA \> 10,000 IU/mL at screening * HCV treatment history: * Treatment-naive for HCV genotypes 1, 2, 3, or 4, or * Treatment-experienced for HCV genotypes 2 or 3 * HIV antiretroviral (ARV) criteria: * On a stable, protocol-approved, HIV ARV regimen with undetectable HIV RNA for \> 8 weeks prior to screening, or * ARV untreated for ≥ 8 weeks prior to screening, with a CD4 T-cell count \> 500 cells/mm\^3 * Presence or absence of cirrhosis; a liver biopsy may be required * Healthy according to medical history and physical examination with the exception of HCV and HIV diagnosis * Agree to use two forms of highly effective contraception for the duration of the study and 6 months after the last dose of study medication

Exclusion criteria

* HCV genotype 1 or 4 with previous HCV treatment * Poor control with HIV ARV regimen requiring a possible dose modification of therapy within 4 weeks of study medication dosing * A new AIDS-defining condition diagnosed within 30 days prior to screening * Prior use of any other inhibitor of the HCV NS5B polymerase * History of any other clinically significant chronic liver disease * Evidence of or history of decompensated liver disease * Chronic hepatitis B virus (HBV) infection * Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers) * Chronic use of immunosuppressive agents or immunomodulatory agents * Clinically relevant drug or alcohol abuse within 12 months of screening * History or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the participant's participation for the full duration of the study or not be in the best interest of the participant in the opinion of the investigator

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)	Posttreatment Week 12	SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ, ie, \< 25 IU/mL) 12 weeks following the last dose of study drug.
Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s)	Up to 24 weeks	The percentage of participants permanently discontinuing any study drug due to an adverse event was summarized.

Secondary

Measure	Time frame	Description
HCV RNA Change From Baseline at Week 2	Baseline; Week 2	—
HCV RNA Change From Baseline at Week 4	Baseline; Week 4	—
Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)	Posttreatment Weeks 4 and 24	SVR4 and SVR24 were defined as HCV RNA \< the lower limit of quantitation (LLOQ) 4 weeks and 24 weeks following the last dose of study drug, respectively.
HCV RNA Change From Baseline at Week 8	Baseline; Week 8	—
Percentage of Participants Experiencing Virologic Failure	Baseline up to Posttreatment Week 24	On-treatment virologic failure was defined as either: * Virologic breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while on treatment), or * Rebound (confirmed \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or * Nonresponse (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment). Virologic relapse was defined as confirmed HCV RNA ≥ LLOQ during the posttreatment period, having achieved HCV RNA \< LLOQ at last on-treatment visit.
HCV RNA Change From Baseline at Week 6	Baseline; Week 6	—
HCV RNA Change From Baseline at Week 1	Baseline; Week 1	—

Countries

Australia, France, Germany, Italy, Spain, United Kingdom

Participant flow

Recruitment details

Participants were enrolled at a total of 39 study sites in Australia and Europe. The first participant was screened on 18 January 2013. The last study visit occurred on 10 July 2014.

Pre-assignment details

346 participants were screened.

Participants by arm

Arm	Count
Genotype 2 Treatment-naive SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 12 weeks in treatment-naive participants with HIV-1 and genotype 2 HCV coinfection	19
Genotype 1 Treatment-naive SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks in treatment-naive participants with HIV-1 and genotype 1 HCV coinfection	112
Genotype 2 Treatment-experienced SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks in treatment-experienced participants with HIV-1 and genotype 2 HCV coinfection	6
Genotype 3 Treatment-naive SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks in treatment-naive participants with HIV-1 and genotype 3 HCV coinfection	57
Genotype 3 Treatment-experienced SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks in treatment-experienced participants with HIV-1 and genotype 3 HCV coinfection	49
Genotype 4 Treatment-naive SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks in treatment-naive participants with HIV-1 and genotype 4 HCV coinfection	31
Total	274

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005
Overall Study	Lack of Efficacy	1	13	1	3	6	5
Overall Study	Lost to Follow-up	0	4	0	2	1	0
Overall Study	Randomized but Not Treated	0	0	0	1	0	0
Overall Study	Withdrew Consent	1	1	0	2	0	0

Baseline characteristics

Characteristic	Total	Genotype 4 Treatment-naive	Genotype 3 Treatment-experienced	Genotype 3 Treatment-naive	Genotype 2 Treatment-experienced	Genotype 2 Treatment-naive	Genotype 1 Treatment-naive
Age, Continuous	47 years STANDARD_DEVIATION 7.4	47 years STANDARD_DEVIATION 5.9	49 years STANDARD_DEVIATION 6.2	47 years STANDARD_DEVIATION 5.4	55 years STANDARD_DEVIATION 10.2	55 years STANDARD_DEVIATION 8.2	45 years STANDARD_DEVIATION 7.6
Cirrhosis Status No	220 participants	23 participants	26 participants	54 participants	4 participants	18 participants	95 participants
Cirrhosis Status Yes	54 participants	8 participants	23 participants	3 participants	2 participants	1 participants	17 participants
HCV RNA Category < 6 log10 IU/mL	81 participants	12 participants	12 participants	21 participants	1 participants	2 participants	33 participants
HCV RNA Category ≥ 6 log10 IU/mL	193 participants	19 participants	37 participants	36 participants	5 participants	17 participants	79 participants
Hepatitis C Virus (HCV) RNA	6.3 log10 IU/mL STANDARD_DEVIATION 0.75	5.9 log10 IU/mL STANDARD_DEVIATION 0.85	6.3 log10 IU/mL STANDARD_DEVIATION 0.77	6.3 log10 IU/mL STANDARD_DEVIATION 0.71	6.4 log10 IU/mL STANDARD_DEVIATION 0.62	6.7 log10 IU/mL STANDARD_DEVIATION 0.66	6.3 log10 IU/mL STANDARD_DEVIATION 0.72
IL28b Status CC	127 participants	9 participants	25 participants	30 participants	3 participants	12 participants	48 participants
IL28b Status CT	106 participants	14 participants	20 participants	21 participants	1 participants	5 participants	45 participants
IL28b Status Missing	1 participants	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants
IL28b Status TT	40 participants	8 participants	4 participants	6 participants	2 participants	2 participants	18 participants
Race/Ethnicity, Customized American Indian/Alaska Native/First Nations	1 participants	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants
Race/Ethnicity, Customized Asian	7 participants	0 participants	0 participants	2 participants	0 participants	0 participants	5 participants
Race/Ethnicity, Customized Black or African American	3 participants	1 participants	0 participants	0 participants	1 participants	0 participants	1 participants
Race/Ethnicity, Customized Hispanic or Latino	16 participants	1 participants	5 participants	3 participants	0 participants	3 participants	4 participants
Race/Ethnicity, Customized Not Hispanic or Latino	255 participants	29 participants	44 participants	54 participants	6 participants	16 participants	106 participants
Race/Ethnicity, Customized Not Permitted	2 participants	1 participants	0 participants	0 participants	0 participants	0 participants	2 participants
Race/Ethnicity, Customized Other	2 participants	0 participants	0 participants	1 participants	0 participants	0 participants	1 participants
Race/Ethnicity, Customized White	259 participants	29 participants	49 participants	54 participants	5 participants	18 participants	104 participants
Sex: Female, Male Female	53 Participants	7 Participants	11 Participants	19 Participants	0 Participants	4 Participants	12 Participants
Sex: Female, Male Male	221 Participants	24 Participants	38 Participants	38 Participants	6 Participants	15 Participants	100 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	17 / 19	45 / 55	166 / 200
serious Total, serious adverse events	0 / 19	5 / 55	10 / 200

Outcome results

Primary

Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s)

The percentage of participants permanently discontinuing any study drug due to an adverse event was summarized.

Time frame: Up to 24 weeks

Population: Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug

Arm	Measure	Value (NUMBER)
Genotype 2 Treatment-naive	Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s)	0 percentage of participants
All Genotype 1 Treatment-naive	Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s)	1.8 percentage of participants
Genotype 1a Treatment-naive	Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s)	3.5 percentage of participants

Primary

Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)

SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ, ie, \< 25 IU/mL) 12 weeks following the last dose of study drug.

Time frame: Posttreatment Week 12

Population: Full Analysis Set: participants who were randomized and received at least 1 dose of study drug. 1 participant with genotype 1 HCV infection did not have subtype information available.

Arm	Measure	Value (NUMBER)
Genotype 2 Treatment-naive	Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)	89.5 percentage of participants
All Genotype 1 Treatment-naive	Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)	84.8 percentage of participants
Genotype 1a Treatment-naive	Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)	84.0 percentage of participants
Genotype 1b Treatment-naive	Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)	90.9 percentage of participants
Genotype 2 Treatment-experienced	Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)	83.3 percentage of participants
Genotype 3 Treatment-naive	Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)	91.2 percentage of participants
Genotype 3 Treatment-experienced	Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)	85.7 percentage of participants
Genotype 4 Treatment-naive	Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)	83.9 percentage of participants

Secondary