Safety, Tolerability, and Antiviral Activity of 24 or 48 Weeks of GS-9190 in Combination With Peginterferon Alfa 2a and Ribavirin for the Treatment of Genotype-1 Chronic HCV Infection

NCT00743795 | Completed Phase 2 DMC

• 1 other identifier: GS-US-196-0103
• Study Type: interventional
• Target: 252
• Locations: 7 countries
• Sites: 72

Brief Summary

The purpose of this study is to compare the safety, tolerability and effectiveness of the experimental drug GS-9190 when administered for 24 or 48 weeks with peginterferon alfa 2a and ribavirin for the treatment of genotype-1 chronic hepatitis C infection.

Conditions

HCV Infection

Keywords

Hepatitis C; HCV; Rapid Virologic Response; Sustained Virologic Response; HCV RNA; Polymerase inhibitor; GS-9190

Outcome Measures

Primary Outcomes (1)

• Undetectable HCV RNA level

  At Week 12 for Early Virologic Response (EVR)

Secondary Outcomes (4)

• Safety and tolerability

  Throughout 72 week study period

• Undetectable HCV RNA level

  Week 4, Week 24 and Week 48

• GS-9190 plasma concentrations

  Through Week 48

• Undetectable HCV RNA

  At Week 72 for sustained virologic response (SVR)

Study Arms (3)

1

PLACEBO COMPARATOR

Peginterferon and ribavirin + placebo BID for 48 weeks + 24 weeks treatment-free follow-up (n = 50)

Drug: placebo; Drug: Peginterferon Alfa 2a; Drug: Ribavirin

2

EXPERIMENTAL

Peginterferon and ribavirin + GS 9190 40 mg BID for 48 weeks + 24 weeks treatment-free follow-up (n = 100)

Drug: GS-9190; Drug: Peginterferon Alfa 2a; Drug: Ribavirin

3

EXPERIMENTAL

Peginterferon and ribavirin + GS 9190 40 mg BID for 48 weeks + 24 weeks treatment-free follow-up. However, subjects who achieve RVR (HCV RNA undetectable at Week 4) and maintain that response through Week 24 will stop all study drugs at Week 24 and be followed for an additional 48 weeks (n = 50).

Drug: GS-9190; Drug: Peginterferon Alfa 2a; Drug: Ribavirin

Interventions

Ribavirin DRUG

Ribavirin supplied as 200 mg Copegus® tablets (1000 mg for subjects weighing \< 75 kg and 1200 mg for subjects weighing ≥ 75 kg) were given in a divided daily dose.

Also known as: RBV

1; 2; 3

placebo DRUG

oral BID

1

GS-9190 DRUG

40 mg oral BID

2; 3

Peginterferon Alfa 2a DRUG

All subjects received a fixed dose of 180 μg PEG via subcutaneous injection on a weekly basis.

Also known as: PEG

1; 2; 3

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult subjects (18 - 70 years of age)
• Chronic HCV infection for at least 6 months prior to Baseline (Day 1) (anti-HCV antibody positive; positive for plasma HCV RNA; medical history consistent with chronicity accepted by the investigator)
• Liver biopsy results within the past 2 years prior to Baseline (Day 1) indicating the absence of cirrhosis
• HCV treatment-naive, defined as no prior exposure to PEG, RIBA, or experimental HCV therapy
• Mono-infection with HCV genotype 1a or 1b
• Detectable plasma HCV RNA at Screening
• BMI between 19 and 36 kg/m2
• Willing and able to provide written informed consent and to comply with all study requirements
• Of generally good health as determined by the Investigator
• Subject agrees to use adequate skin protection (e.g., sunblocking agent) when exposed to the sun.
• Women of childbearing potential (i.e., a non-menopausal female or a female with menopausal \< 2 years, who has not had a hysterectomy, bilateral oophorectomy or medically documented ovarian failure) must have negative serum β-human chorionic gonadotropin (hCG) at screening and negative urine pregnancy test prior to the first study drug administration.
• All subjects (male and female) must agree to utilize highly effective contraception methods (two separate forms of contraception, one of which must be an effective barrier method, or be non-heterosexually active, practice sexual abstinence or have a vasectomized partner) from screening throughout the duration of study treatment and for 24 weeks after the last dose of RIBA.
• Female subjects who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing.
• Female subjects who are postmenopausal for less than two years are required to have FSH \> 40 mIU/mL. If the FSH is ≤ 40 mIU/mL, the subject must agree to use highly effective method of birth control (as described above) to participate in the study.
• Male subjects who are sexually active must be willing to use effective barrier contraception (e.g., condom with spermicide) during heterosexual intercourse from screening through completion of the study and continue for 24 weeks after the last dose of RIBA

You may not qualify if:

• Pregnant or breast feeding women or women who may wish to become pregnant during the course of the study
• Males who have partners planning to become pregnant
• Males and females of reproductive potential who are unwilling to use two forms of effective birth control through Study Week 72. One method should include a condom with spermicide for males
• Infection with non-genotype 1 HCV
• Poorly controlled diabetes mellitus (hemoglobin A1c \> 7) unless treatment intervention has been reviewed with the Medical Monitor and improved glucose control is anticipated
• History of sarcoidosis
• History of hemoglobinopathy (e.g., thalassemia)
• History of known retinal disease
• History of invasive malignancy diagnosed or treated within 5 years (recent localized treatment of squamous or non-invasive basal cell skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to screen)
• Evidence of hepatocellular carcinoma
• Chronic liver disease of a non-HCV etiology
• Untreated or significant psychiatric illnesses including severe depression, schizophrenia, psychosis, or a history of a suicide attempt
• Co-infection with HIV, HBV, or multiple HCV genotypes
• Chronic use of systemic immunosuppressive agents
• Presence of autoimmune disorders. Subjects with treated hypothyroidism with normal TSH may be enrolled.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (72)

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Anaheim, California, 92801, United States

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Los Angeles, California, 90048, United States

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Newport Beach, California, 92663, United States

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San Clemente, California, 92673, United States

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San Diego, California, 92115, United States

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San Diego, California, 92123, United States

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San Francisco, California, 94115, United States

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Englewood, Colorado, 80110, United States

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Miami, Florida, 33136, United States

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North Miami Beach, Florida, 33162, United States

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Orlando, Florida, 32803, United States

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Sarasota, Florida, 34243, United States

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Tampa, Florida, 33613, United States

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Atlanta, Georgia, 30308, United States

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Decatur, Georgia, 30033, United States

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Chicago, Illinois, 60611, United States

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Bowling Green, Kentucky, 42101, United States

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Baton Rouge, Louisiana, 70809, United States

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Baltimore, Maryland, 21201, United States

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Baltimore, Maryland, 21229, United States

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Baltimore, Maryland, 21287, United States

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Boston, Massachusetts, 02114, United States

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Detroit, Michigan, 48202, United States

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St Louis, Missouri, 63104, United States

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Cedar Knolls, New Jersey, 07927, United States

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Johnson City, New York, 13790, United States

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New York, New York, 10016, United States

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New York, New York, 10021, United States

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New York, New York, 10029-6574, United States

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New York, New York, 10032, United States

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Plainview, New York, 11803, United States

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Syracuse, New York, 13210, United States

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Asheville, North Carolina, 28801, United States

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Durham, North Carolina, 27710, United States

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High Point, North Carolina, 27262, United States

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Cincinnati, Ohio, 45219, United States

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Cincinnati, Ohio, 45267, United States

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Tulsa, Oklahoma, 74104, United States

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Philadelphia, Pennsylvania, 19104, United States

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Philadelphia, Pennsylvania, 19140, United States

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Germantown, Tennessee, 38138, United States

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Dallas, Texas, 75208, United States

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Houston, Texas, 77090, United States

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San Antonio, Texas, 78215, United States

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Annandale, Virginia, 22003-6800, United States

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Fairfax, Virginia, 22031, United States

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Norfolk, Virginia, 23502-3927, United States

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Richmond, Virginia, 23298, United States

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Brussels, B-1070, Belgium

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Brussels, B-1200, Belgium

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Ghent, B-9000, Belgium

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Leuven, Belgium

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Liège, Belgium

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Berlin, 10969, Germany

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Cologne, 50921, Germany

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Frankfurt, 60590, Germany

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Hamburg, 20099, Germany

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Hanover, 30625, Germany

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München, 80336, Germany

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Dublin, 8, Ireland

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Dublin, 9, Ireland

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Dublin, Ireland

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Bialystok, 15-540, Poland

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Bydgoszcz, 85-030, Poland

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Chorzów, Poland

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Czeladź, 41-250, Poland

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Krakow, 31-501, Poland

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Warsaw, 01-201, Poland

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Santurce, 00909, Puerto Rico

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Birmingham, B15 2TH, United Kingdom

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London, E1 1BB, United Kingdom

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London, United Kingdom

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MeSH Terms

Conditions

Hepatitis C

Interventions

tegobuvir; peginterferon alfa-2a; Ribavirin

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

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Steven Knox

  Gilead Sciences

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2008
• First Posted: August 29, 2008
• Study Start: October 1, 2008
• Primary Completion: July 1, 2009
• Study Completion: September 1, 2013
• Last Updated: November 5, 2013

Record last verified: 2013-10

Locations

GB (3); BE (5); PR (1); US (48); DE (6); IE (3); PL (6)