Efficacy and Safety of Sofosbuvir Plus Ribavirin in Chronic Genotype 1, 2 and 3 Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) Co-infected Adults

Hepatitis C Clinical Trial

Official title:

A Phase 3, Open-label Study to Investigate the Efficacy and Safety of GS-7977 Plus Ribavirin in Chronic Genotype 1, 2 and 3 Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) Co-infected Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01667731
• Other study ID #: GS-US-334-0123
• Status: Completed
• Phase: Phase 3
• First received: August 9, 2012
• Last updated: November 14, 2014
• Start date: July 2012
• Est. completion date: February 2014

Study information

• Verified date: November 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy, safety, and tolerability of sofosbuvir (SOF; GS-7977) plus ribavirin (RBV) in adults with chronic genotypes 1, 2, and 3 HCV infection who are coinfected with HIV-1.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 224
• Est. completion date: February 2014
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Willing and able to provide written informed consent

• Male or female, age = 18 years with chronic HCV and HIV-1 infection

• HCV RNA > 1 x 10^4 IU/mL at screening

• Infection with HCV genotype 1, 2 or 3 as determined at screening

• HIV-1 infection confirmed with positive ELISA or Western blot at screening

• Medical records must be sufficient to be categorized on interferon (IFN) eligibility or prior treatment history with PEG/RBV.

• Confirmation of chronic HCV infection

• Ability to determine presence/absence of cirrhosis.

• HIV antiretroviral therapy (ARV) criteria of one of the following:

• ARV untreated with a CD4 T-cell count > 500 cells/mm^3

• On a stable, protocol-approved, ARV for > 8 weeks prior to screening with a CD4 T-cell count > 200 cells/mm^3 and a documented undetectable plasma HIV-1 RNA level for = 8 weeks preceding the screening visit

• Approved HIV antiretroviral medications based on drug interaction studies

• Not been treated with any investigational drug or device within 30 days of the screening visit

• Females if confirmed that she is not pregnant or nursing of non-childbearing potential or of childbearing potential but has a negative serum pregnancy test at screening and agrees to use protocol approved method of birth control from screening through 6 months after the last dose of RBV

• Males who agree to consistently and correctly use a condom while their female partner agrees to use protocol approved method of birth control from screening through 7 months after the last dose of RBV

• Must be of generally good health as determined by the investigator.

• Liver imaging within 6 months of baseline/Day 1 is required in cirrhotic patients only, to exclude hepatocellular carcinoma (HCC)

Exclusion Criteria:

• Non-genotype 1/2/3 or mixed genotype at screening

• Genotype 1 with prior treatment for HCV

• Poor control with ARV regimen

• Prior exposure to a direct-acting antiviral targeting the HCV nonstructural protein (NS)5B polymerase

• Chronic liver disease of a non-HCV etiology (eg, hemochromatosis, Wilson's disease, a1 antitrypsin deficiency, cholangitis)

• A new AIDS-defining condition diagnosed within 30 days prior to screening

• Active, serious infection (other than HIV or HCV) requiring parenteral antibiotics, antivirals or antifungals within 30 days prior to baseline

• Infection with hepatitis B virus (HBV)

• Contraindication to RBV therapy

• Chronic use of systemically administered immunosuppressive agents (eg, prednisone equivalent > 10 mg/day)

• History of solid organ transplantation or malignancy diagnosed or treated within 5 years

• Current or prior history of clinical hepatic decompensation or other significant gastrointestinal disorder

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Hepatitis
• Hepatitis A
• Hepatitis C
• HIV Infections
• Human Immunodeficiency Virus
• Immunologic Deficiency Syndromes

Intervention

Drug:
• SOF
Sofosbuvir (SOF) 400 mg tablet administered orally once daily
• RBV
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)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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) at 12 weeks after stopping study treatment.	Posttreatment Week 12	No
Primary	Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s)	The percentage of participants discontinuing any study drug due to an adverse event was summarized.	Up to 24 weeks	No
Secondary	Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)	SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.	Posttreatment Weeks 4 and 24	No
Secondary	Change From Baseline in HCV RNA at Week 1		Baseline; Week 1	No
Secondary	Change From Baseline in HCV RNA at Week 2		Baseline; Week 2	No
Secondary	Change From Baseline in HCV RNA at Week 4		Baseline; Week 4	No
Secondary	Change From Baseline in HCV RNA at Week 6		Baseline; Week 6	No
Secondary	Change From Baseline in HCV RNA at Week 8		Baseline; Week 8	No
Secondary	Percentage of Participants Experiencing On-treatment Virologic Failure	On-treatment virologic failure was defined as: Viral breakthrough: HCV RNA = LLOQ after having previously had HCV RNA < LLOQ while on treatment, confirmed with 2 consecutive values (second confirmation value may have been posttreatment) or with a last available on-treatment measurement and no subsequent follow-up values, or; Viral rebound: > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values (second confirmation value may have been posttreatment) or with a last available on-treatment measurement and no subsequent follow-up values, or; Nonresponse: HCV RNA persistently = LLOQ through 8 weeks of treatment	Up to 24 weeks	No
Secondary	Percentage of Participants Experiencing Viral Relapse	Viral relapse was defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) at end of treatment, but did not achieve an SVR.	Up to Posttreatment Week 24	No