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

NCT01667731 | Completed Phase 3 Results DMC

• 1 other identifier: GS-US-334-0123
• Study Type: interventional
• Target: 224
• Locations: 2 countries
• Sites: 27

Brief 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.

Conditions

Hepatitis C; Human Immunodeficiency Virus

Keywords

Hepatitis C; Chronic; HCV; HIV; Human Immunodeficiency Virus; Co-Infected

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (8)

• Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)

  Posttreatment Weeks 4 and 24

• Change From Baseline in HCV RNA at Week 1

  Baseline; Week 1

• Change From Baseline in HCV RNA at Week 2

  Baseline; Week 2

• Change From Baseline in HCV RNA at Week 4

  Baseline; Week 4

• Change From Baseline in HCV RNA at Week 6

  Baseline; Week 6

Study Arms (3)

SOF+RBV 12 Weeks (GT 2/3, TN)

EXPERIMENTAL

Treatment-naive (TN) participants coinfected with HIV-1 and genotype (GT) 2 or genotype 3 HCV infection will receive SOF+RBV for 12 weeks.

Drug: SOF; Drug: RBV

SOF+RBV 24 Weeks (GT 2/3, TE)

EXPERIMENTAL

Treatment-experienced (TE) participants coinfected with HIV-1 and genotype 2 or genotype 3 HCV infection will receive SOF+RBV for 24 weeks.

Drug: SOF; Drug: RBV

SOF+RBV 24 Weeks (GT 1, TN)

EXPERIMENTAL

Treatment-naive (TN) participants coinfected with HIV-1 and genotype 1 HCV infection will receive SOF+RBV for 24 weeks.

Drug: SOF; Drug: RBV

Interventions

SOF DRUG

Sofosbuvir (SOF) 400 mg tablet administered orally once daily

Also known as: GS-7977, PSI-7977, Sovaldi®

SOF+RBV 12 Weeks (GT 2/3, TN); SOF+RBV 24 Weeks (GT 1, TN); SOF+RBV 24 Weeks (GT 2/3, TE)

RBV DRUG

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)

SOF+RBV 12 Weeks (GT 2/3, TN); SOF+RBV 24 Weeks (GT 1, TN); SOF+RBV 24 Weeks (GT 2/3, TE)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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, α1 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (27)

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Birmingham, Alabama, United States

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Coronado, California, United States

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Los Angeles, California, United States

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Lutherville, California, United States

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Oakland, California, United States

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Sacramento, California, United States

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San Francisco, California, United States

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Torrance, California, United States

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Washington D.C., District of Columbia, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Tampa, Florida, United States

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Chicago, Illinois, United States

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Springfield, Massachusetts, United States

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Kansas City, Missouri, United States

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Hillsborough, New Jersey, United States

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Santa Fe, New Mexico, United States

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New York, New York, United States

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Chapel Hill, North Carolina, United States

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Durham, North Carolina, United States

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Allentown, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Providence, Rhode Island, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Seattle, Washington, United States

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San Juan, Puerto Rico

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Related Publications (3)

• Saeed S, Strumpf EC, Walmsley SL, Rollet-Kurhajec K, Pick N, Martel-Laferriere V, Hull M, Gill MJ, Cox J, Cooper C, Klein MB; Canadian Co-Infection Cohort Study; Cohen J, Conway B, Cooper C, Cote P, Cox J, Gill J, Haider S, Harris M, Haase D, Hull M, Montaner J, Moodie E, Pick N, Rachlis A, Rouleau D, Sandre R, Tyndall JM, Vachon ML, Walmsley S, Wong D. How Generalizable Are the Results From Trials of Direct Antiviral Agents to People Coinfected With HIV/HCV in the Real World? Clin Infect Dis. 2016 Apr 1;62(7):919-926. doi: 10.1093/cid/civ1222. Epub 2016 Jan 6.

  PMID: 26743093 DERIVED

• Younossi ZM, Stepanova M, Sulkowski M, Naggie S, Puoti M, Orkin C, Hunt SL. Sofosbuvir and Ribavirin for Treatment of Chronic Hepatitis C in Patients Coinfected With Hepatitis C Virus and HIV: The Impact on Patient-Reported Outcomes. J Infect Dis. 2015 Aug 1;212(3):367-77. doi: 10.1093/infdis/jiv005. Epub 2015 Jan 12.

  PMID: 25583164 DERIVED

• Sulkowski MS, Naggie S, Lalezari J, Fessel WJ, Mounzer K, Shuhart M, Luetkemeyer AF, Asmuth D, Gaggar A, Ni L, Svarovskaia E, Brainard DM, Symonds WT, Subramanian GM, McHutchison JG, Rodriguez-Torres M, Dieterich D; PHOTON-1 Investigators. Sofosbuvir and ribavirin for hepatitis C in patients with HIV coinfection. JAMA. 2014 Jul 23-30;312(4):353-61. doi: 10.1001/jama.2014.7734.

  PMID: 25038354 DERIVED

MeSH Terms

Conditions

Hepatitis C; Acquired Immunodeficiency Syndrome; Bronchiolitis Obliterans Syndrome

Interventions

Sofosbuvir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; HIV Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences, Inc.

ClinicalTrialDisclosures@gilead.com

Study Officials

• Anuj Gaggar, MD, PhD

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2012
• First Posted: August 17, 2012
• Study Start: July 1, 2012
• Primary Completion: November 1, 2013
• Study Completion: February 1, 2014
• Last Updated: November 21, 2014
• Results First Posted: November 21, 2014

Record last verified: 2014-11

Locations

US (26); PR (1)