Study Stopped
Termination of study was due to safety reasons
Chronically-infected HCV Genotype 2 and 3 Treatment-naive Subjects: Part A: Safety and Efficacy of INX-08189 With Peg IFN Alfa-2a and Ribavirin. Part B: INX-08189 in Interferon Free Treatment With Daclatasvir and/or Ribavirin
A Phase II, Randomized, Multi-center, Two Part Study of the Safety and Efficacy of Double-blind, Placebo-controlled INX-08189 in Adjunctive Treatment With Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®) in Study Part A, and Open-label INX-08189 in Adjunctive (Interferon Free) Treatment With Daclatasvir and/or Ribavirin (Copegus®) in Study Part B, in Chronically-infected HCV Genotype 2 and 3 Treatment-naive Subjects
2 other identifiers
interventional
210
1 country
6
Brief Summary
Part A: The purpose of this study is to evaluate the safety and tolerability of INX-08189 and placebo with Peginterferon alfa-2a and Ribavirin during 12 weeks of treatment Part B: The purpose of this study is to evaluate the safety and tolerability of INX-08189 with Ribavirin or INX-08189 with Daclatasvir or INX-08189 with Daclatasvir and Ribavirin
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2012
Shorter than P25 for phase_2
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 25, 2011
CompletedFirst Posted
Study publicly available on registry
August 30, 2011
CompletedStudy Start
First participant enrolled
May 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2013
CompletedNovember 4, 2015
October 1, 2015
1.3 years
August 25, 2011
October 12, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Part A: Change in Hepatitis C Viral Load Measurements at protocol specific timepoints
Weeks -6, 0, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 36, 48
Part B: proportion of subjects with SVR defined as HCV RNA ≤ LOQ (Limit of Quantitation)
* SVR = Sustained virologic response * HCV RNA = Hepatitis C virus ribonucleic acid
At treatment weeks 12
Part B: proportion of subjects with SVR defined as HCV RNA ≤ LOQ
Post treatment week 12
Safety assessments is measured by Physical Exams, vital signs, laboratory assessments, ECGs, pregnancy test, viral resistance testing, adverse event assessment
up to 1 year
Secondary Outcomes (4)
Proportion of subjects with RVR (Rapid Virologic Response), undetectable HCV RNA
At treatment weeks 4
Proportion of subjects with Complete EVR (Early Virologic Response), undetectable HCV RNA
At treatment weeks 12
Proportion of subjects with Extended RVR
At treatment weeks 4 and 12
Proportion of subjects with SVR24
Post treatment week 24
Study Arms (9)
25 mg INX-08189 + Pegylated interferon alfa-2a + Ribavirin
EXPERIMENTALPART A Arm 1
50 mg INX-08189 + Pegylated interferon alfa-2a + Ribavirin
EXPERIMENTALPART A Arm 2
100 mg INX-08189 + Pegylated interferon alfa-2a + Ribavirin
EXPERIMENTALPART A Arm 3
Placebo + Pegylated interferon alfa-2a + Ribavirin
PLACEBO COMPARATORPART A Arm 4
100 mg INX-08189 + Ribavirin
EXPERIMENTALPART B Arm 1
200 mg INX-08189 + Ribavirin
EXPERIMENTALPART B Arm 2
Daclatasvir + INX-08189 100 mg
EXPERIMENTALPART B Arm 3
Daclatasvir + INX-08189 200 mg
EXPERIMENTALPART B Arm 4
Daclatasvir + INX-08189 50 mg + Ribavirin
EXPERIMENTALPART B Arm 5
Interventions
Tablet, Oral, 25 mg, Once daily (QD), 12 weeks
Tablet, Oral, 0 mg, Once daily (QD), 12 weeks
Syringe, Subcutaneous injection, 180 μg, Once per week, 12 weeks
Tablet, Oral, 500 or 600 mg weight dependent, Twice daily (BID), 12 weeks
Tablet, Oral, 60 mg, QD, 12 weeks
Eligibility Criteria
You may qualify if:
- Amendment 4: Genotype 1, 10 subjects at site 401.
- Males and females, 18 to 65 years of age inclusive with a body mass index (BMI) of at least 18 kg/m2 but not exceeding 36 kg/m2
- Diagnosed with chronic HCV at least 6 months prior to Visit 1 with medical documentation (e.g., prior PCR result, prior liver biopsy, prior genotyping, etc.), with a positive HCV viral load of at least 50,000 IU/mL at Visit 1 (screening) as measured by quantitative PCR
- Chronic genotype 2 or 3 HCV infection (per polymerase chain reaction \[PCR\] methodology)
- HCV treatment-naïve where "treatment-naïve" is defined as no prior treatment with IFN alfa 2a or 2b, Pegylated IFN alfa-2a, Ribavirin, or any HCV direct-acting anti-viral drugs
- Liver biopsy consistent with chronic HCV infection but with a classification of non-cirrhotic (and without classification of 'transition to cirrhosis or borderline cirrhosis') as judged by a pathologist (defined as Knodell ≤ 3, Metavir ≤ 2, Ishak ≤ 4, or Batts \&Ludwig ≤ 2 ) within the last two years and before Visit 2 (biopsy can be done after Visit 1 and before Visit 2, within the screening period)
- Negative urine drug screen for drugs of abuse and methadone (via central lab-provided dipstick at site) at screening (Visit 1) (note: subjects with a valid prescription for a drug which can be abused \[e.g., benzodiazepine, opiates\] can be enrolled on the judgment of the investigator)
- Females will have a negative serum beta human chorionic gonadotropin (βHCG) pregnancy test at screening and a negative urine dipstick pregnancy test on Study Day 0 (visit 2)
- Agreement by both female subjects of childbearing potential and male subjects (who have not been surgically sterilized) to practice an acceptable method of birth control, which includes at least one barrier during the study and for at least 6 months after the cessation of treatment. Surgical sterilization of either the female or the male partner must have occurred at least 6 months prior to the first dose and females must be post-menopausal for 2 years to be considered of non-child-bearing potential. Acceptable contraceptive methods include one of the following: Oral and implantable hormonal contraceptives by the female partner for at least 3 months prior to the first dose of Study Drug with additional use of a barrier method, IUD in place for at least 6 months prior to first dose with additional use of barrier method. Acceptable barrier methods include either diaphragm with spermicide, and condom with spermicide. (Note: Abstinence is not an acceptable method of birth control, subjects who indicate sexual inactivity must agree to utilize an acceptable method of birth control in the event of sexual activity)
- Willing and able to complete all study visits and procedures, and able to effectively communicate with the investigator and other testing center personnel
- Signed informed consent form (ICF) executed prior to protocol screening assessments
You may not qualify if:
- Signs or symptoms of decompensated liver disease such as variceal bleeding, ascites, hepatic encephalopathy, active jaundice defined by an indirect bilirubin \> 2, Alanine transaminase (ALT) or Aspartate aminotransferase (AST) laboratory values ≥ 10 times the upper limit of normal, or other evidence of decompensated liver disease, or hepatocellular carcinoma
- Chronic liver disease other than HCV not limited to Hepatitis B virus (HBV) \[positive test for hepatitis B surface antigen (HBsAg)\], hemochromatosis, auto-immune hepatitis, alcoholic liver disease or non-alcoholic fatty liver disease
- History of liver transplantation
- Co-infection with Human immunodeficiency virus (HIV) \[positive test for anti-HIV Ab\] or use of didanosine
- History of a heart attack, cardiac ischemia, heart disease, clinically symptomatic cardiac abnormalities, or blood clots, based on medical history or apparent on physical exam
- QTcF interval at Visit 1 of greater than or equal to 450 ms by Fridericia's correction, or a personal or family history of Torsades de Pointe
- History or presence of sarcoidosis or pancreatitis
- History or presence of severe pulmonary function impairment including severe (\> GOLD stage III) chronic obstructive pulmonary obstructive disease, and moderate to severe asthma
- Uncontrolled diabetes mellitus as evidenced by HbA1C ≥ 8.5% at screening (Visit 1)
- Use of the following medications concurrently or within the 30 days prior to Screening (Visit 1) associated with QT prolongation: macrolides, antiarrhythmic agents, azoles, fluoroquinolones, and tricyclic anti-depressants (specifically excluded medication will be listed in protocol Section 6.8)
- Use of immunosuppressive or immune-modulating agents (including azathioprine, corticosteroids and immunosuppressive agents) or presence of an immunologically-mediated autoimmune disease (other than asthma) or history of solid organ or bone marrow transplantation (note: inhaled steroids for mild/moderate asthma and topical steroid for minor skin conditions allowed and washout period for per Oral (PO)/Intramuscular (IM)/ Intravenous (IV) corticosteroid use is 8 weeks; washout periods for other immunosuppressives determined by Medical Monitor)
- Use of strong CYP3A4-inhibiting protease inhibitors (specifically Atazanavir, Indinavir, Nelfinavir, Saquinavir, and Ritonavir), strong CYP3A4 inhibitors (specifically Clarithromycin, Itraconazole, Ketoconazole, Nefazodone, Telithromycin), or strong CYP3A4 inducers (specifically Rifampin, Efavirenz, Etravirine, Phenobarbital, Phenytoin, and Carbamazepine)
- Absolute neutrophil count of \< 1800 cells/mm3, or platelet count \< 130,000 cells/mm3, or hemoglobin \< 12 g/dl for women and \< 13 g/dl for men, or a history of anemia, sickle cell anemia, or thalassemia; (note: if baseline value within 5% of minimum qualifying value, one re-test allowed for the purpose of qualifying for study)
- A history or presence of abnormal thyroid function that is not adequately controlled \[defined as Thyroid-stimulating hormone (TSH) levels less than 0.8 x lower limit of normal (LLN) or greater than 1.2 x the upper limit of normal (ULN)\]
- Creatinine clearance \< 50 mL/minute, serum creatinine concentration ≥ 1.5 times the ULN, or albumin ≤ 3 g/dl
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (6)
Acri Phase One
Anaheim, California, 92801, United States
Scripps Health Dba Scripps Clinical Research Services
La Jolla, California, 92037, United States
Quest Clinical Research
San Francisco, California, 94115, United States
Kansas City Cancer Centers, Llc.
Kansas City, Missouri, 64111, United States
Options Health Research, Llc
Tulsa, Oklahoma, 74104, United States
Alamo Medical Research
San Antonio, Texas, 78215, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Bristol-Myers Squibb
Bristol-Myers Squibb
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 25, 2011
First Posted
August 30, 2011
Study Start
May 1, 2012
Primary Completion
August 1, 2013
Study Completion
August 1, 2013
Last Updated
November 4, 2015
Record last verified: 2015-10