Clinical trial NCT01371578: Oral Antivirals (GS-5885, Tegobuvir, and/or GS-9451) With Peginterferon Alfa 2a and Ribavirin in Treatment Experienced Subjects With Chronic Genotype 1 Hepatitis C Virus Infection
Official title: A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Response Guided Therapy Using Combinations of Oral Antivirals (GS-5885, Tegobuvir, and/or GS-9451) With Peginterferon Alfa 2a and Ribavirin in Treatment Experienced Subjects With Chronic Genotype 1 Hepatitis C Virus Infection (Protocol GS US 256 0124)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C, Chronic
Keywords: Hepatitis C
HCV
Rapid Virologic Response
Sustained Virologic Response
Direct Acting Antiviral
Combination Therapy HCV RNA
Polymerase inhibitor
Protease inhibitor
Treatment naïve
GS-5885
GS-9190
Tegobuvir
GS-9451
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2011-06-13
Enrollment: 163
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Response Guided Therapy using Combinations of Oral Antivirals (GS-5885, tegobuvir, and/or GS-9451) with Peginterferon Alfa 2a and Ribavirin in Treatment Experienced Subjects with Chronic Genotype 1 Hepatitis C Virus (HCV) Infection.

Detailed description: In September 2011, the FDA requested that Gilead make several major changes to this study because of side effects experienced by two patients in other Gilead studies.

In 2 HCV-infected people that were given tegobuvir with another experimental medication plus interferon and ribavirin, big reductions in the number of white blood cells, red blood cells and platelets were seen. Because these cases might have been related to tegobuvir when given with interferon, ribavirin and another direct antiviral agent, tegobuvir is no longer being given to people with these other medications in this study.

As a result, the study is now open label which means both you and your study doctor will know the medication you will be receiving and Arms 1 and 3 have been discontinued from the study.

All subjects enrolled in the study as of September 2nd 2011 will receive Response Guided Therapy (RGT) with both GS-5885 and GS-9451 plus PEG and RBV.

Eligibility criteria: Inclusion Criteria:

* Male or female, aged from 18 to 70 years old, inclusive
* Chronic HCV infection for at least 6 months prior to Baseline
* Subjects must have liver biopsy results (≤ 3 years prior to screening) indicating the absence of cirrhosis.
* Monoinfection with HCV genotype 1
* HCV RNA \> 10\^4 IU/mL at Screening
* Prior treatment and adherence (as defined by receiving at least 80% of the prescribed treatment) with one course of a pegylated interferon-alfa (Pegasys or Peg-Intron) and RBV
* The subject's medical records must include sufficient detail of prior treatment with pegylated interferon-alfa and RBV (start/stop dates and viral response) to allow for categorization of prior response as either

  * Non-Responder: Subject did not achieve undetectable HCV RNA levels during or at the end of a treatment period of at least 12 weeks duration. Within Nonresponders, subjects will be further defined as Null or Partial Responders if they had \< 2 log10 or ≥ 2 log10 reduction, respectively, in HCV RNA during the first 12 weeks of treatment
  * Responder: Subject achieved undetectable HCV RNA during treatment. Within Responders, subjects will be further defined as Relapsers if they had undetectable HCV RNA at the end of at least 42 weeks of treatment but detectable HCV RNA levels observed within 1 year of the end of treatment and Breakthrough subjects if they achieved undetectable HCV RNA levels during the treatment period but detectable HCV RNA at the end of treatment.
* No prior treatment with an oral HCV antiviral (exclusive of RBV).
* Body mass index (BMI) 18-36 kg/m2, inclusive.
* Screening ECG without clinically significant abnormalities and with QTcF interval (QT corrected using Fridericia's formula) ≤ 450 msec for males and ≤ 470 msec for females
* Creatinine clearance ≥ 50 mL/min.
* Agree to use two forms of highly effective contraception for the duration of the study and for 6 months after the last dose of study medication. Females of childbearing potential must have a negative pregnancy test at Screening and Baseline

Exclusion Criteria:

* Discontinued prior treatment with pegylated interferon-alfa and RBV due to an adverse event, toxicity reasons or were lost to follow-up.
* Exceed defined thresholds for leukopenia, neutropenia, anemia, thrombocytopenia, thyroid stimulating hormone (TSH)
* Diagnosis of autoimmune disease, decompensated liver disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), HIV, hepatitis B virus (HBV), or another HCV genotype, hepatocellular carcinoma or other malignancy (with exception of certain skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed.
* Current use of amphetamines, cocaine, opiates (e.g., morphine, heroin), or ongoing alcohol abuse are excluded. Subjects on stable methadone are excluded, however stable buprenorphine maintenance treatment for at least 6 months is not exclusionary
* Receiving any of the prohibited concomitant medications.

Primary outcomes:
measure: Sustained Virologic Response (SVR)
timeFrame: through 24 weeks of off-treatment follow-up
Secondary outcomes:
measure: Sustained Virologic Response(SVR) of each regimen administered for 24 to 48 weeks
timeFrame: Weeks 1, 2, 4, 8, 12, 16, 20, 24, 36, 48 and at 4 and 12 weeks off-treatment
measure: Safety and Tolerability
timeFrame: through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up
measure: Characterize the viral dynamics of GS-5885, GS-9451 when administered in combination with PEG and RBV
timeFrame: Through Week 2 of therapy
measure: Characterize the pharmacokinetics of GS-5885 and GS-9451 when administered in combination with PEG and RBV
timeFrame: Through Week 2 of therapy
measure: Emergence of Viral Resistance
timeFrame: through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Digestive Health Specialists of the Southeast
state: Alabama
city: Montgomery
country: United States
facility: Alabama Liver and Digestive Specialists
state: Alabama
city: Beverly Hills
country: United States
facility: California Liver Institute
state: California
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: San Diego
country: United States
facility: RESEARCH and EDUCATION, INC
state: California
city: San Diego
country: United States
facility: Medical Associates Research Group
state: California
city: San Diego
country: United States
facility: Kaiser Permanente
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Englewood
country: United States
facility: South Denver Gastroenterology
state: Colorado
city: Bradenton
country: United States
facility: Bach and Godofsky Infectious Diseases
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Wellington
country: United States
facility: South Florida Center of Gastroenterology, LLC
state: Florida
city: Atlanta
country: United States
facility: Emory University, Infectious Disease Clinic
state: Georgia
city: Atlanta
country: United States
facility: Digestive Healthcare of Georgia
state: Georgia
city: Decatur
country: United States
facility: Dekalb Gastroenterology
state: Georgia
city: Marietta
country: United States
facility: Gastrointestinal Specialists of Georgia PC
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Indianapolis
country: United States
facility: Indianapolis Gastroenterology Research Foundation
state: Indiana
city: Bowling Green
country: United States
facility: Graves Gilbert Clinic
state: Kentucky
city: Baton Rouge
country: United States
facility: Gastroenterology Associates, LLC
state: Louisiana
city: Baltimore
country: United States
facility: Digestive Disease Associates, PA
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: Partners in Internal Medicine, P.C.
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Jackson
country: United States
facility: Gastrointestinal Associates, PA
state: Mississippi
city: Tupelo
country: United States
facility: Digestive Health Specialists, PA
state: Mississippi
city: Hillsborough
country: United States
facility: ID Care 105
state: New Jersey
city: Morristown
country: United States
facility: Atlantic Research Affiliates, LLC
state: New Jersey
city: Santa Fe
country: United States
facility: Southwest CARE Center
state: New Mexico
city: Binghamton
country: United States
facility: Binghamton Gastroenterology
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Concorde Medical Group
state: New York
city: New York
country: United States
facility: Cornell University Gastroenterology & Hepatology
state: New York
city: Asheville
country: United States
facility: Asheville Gastroenterology Associates, P.A.
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Fayetteville
country: United States
facility: Cumberland Research Associates, LLC
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Tulsa
country: United States
facility: Options Health Research, LLC
state: Oklahoma
city: Providence
country: United States
facility: University Gastroenterology
state: Rhode Island
city: Germantown
country: United States
facility: Memphis Gastroenterology Group
state: Tennessee
city: Nashville
country: United States
facility: Columbia Medical Group, The Frist Clinic
state: Tennessee
city: Nashville
country: United States
facility: Nashville Medical Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Nashville Gastrointestinal Specialists, Inc
state: Tennessee
city: Arlington
country: United States
facility: The North Texas Research Institute
state: Texas
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Houston
country: United States
facility: Kelsey Research Foundation
state: Texas
city: Houston
country: United States
facility: Research Specialists of Texas
state: Texas
city: Fairfax
country: United States
facility: Metropolitan Research
state: Virginia
city: Norfolk
country: United States
facility: Digestive and Liver Disease Specialists
state: Virginia
city: Richmond
country: United States
facility: Liver Institute of Virginia
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center, Digestive Disease Institute
state: Washington
city: San Juan
country: Puerto Rico
facility: Fundacion de Investigacion de Diego
Study officials:
affiliation: Gilead Sciences
name: Bittoo Kanwar, MD
role: STUDY_CHAIR
References: