GS-US-283-0106

Overview

Status: Recruiting
Keywords: Hepatitis , Never been treated , Hepatitis B
IRB Number: 00057493
Specialty: Gastroenterology
Sub Specialties: Hepatology

Brief Summary

Purpose

GS-9620 is an experimental (investigational) drug being tested as a possible treatment of chronic HBV infection.  An investigational drug is one that is not yet approved by the United States Food and Drug Administration (FDA).  GS-9620 works by stimulating cells in the body to make interferon.  Interferon is part of the body’s natural defense system against infection. The purpose of this study is to determine how well the body tolerates GS-9620, how long GS-9620 stays in the body, and how GS-9620 affects the HBV infection in the body.  The study is for research purposes only and is not intended or expected to cure any medical conditions.

Objectives

 The primary objective of this study is as follows:

To evaluate the safety and tolerability of escalating single and multiple (two) oral doses of GS-9620 in treatment naive subjects with chronic HBV infection

The secondary objectives of this study are as follows:

To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of GS-9620 in treatment naive subjects with chronic HBV infection

To evaluate the antiviral activity of GS-9620 against HBV infection in treatment naive subjects (as determined by effects on HBsAg and HBV DNA)

The exploratory objectives of this study are as follows:

To characterize the PD/antiviral activity relationship

To characterize the relationship between biomarkers and outcomes

Principal Investigator: Terry Box
Department: Gastroenterology
Co Investigator:

Contact Information

Name:Cameron Hill
Phone: 801-587-3608
Email: cameron.hill@utah.edu

Inclusion Criteria

 

Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this study.
1. Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures.
2. Male or female, aged from 18 to 65 years old, inclusive
3. Subjects must, in the opinion of the Investigator, be in good general health based upon medical history, physical examination (including vital signs), and Screening laboratory evaluations (hematology, chemistry, and urinalysis must fall within the central laboratory’s reference normal ranges unless the results have been determined by the Investigator to have no clinical significance)4. Chronic HBV infection defined as one of the following:
• HBsAg or HBV DNA positivity for at least 6 months
• Medical records indicating a chronic HBV infection
5. HBsAg ≥ 250 IU/mL
6. HBV treatment naïve
• Subjects who have received less than 4 weeks of therapy with an anti-HBV therapy may be considered for treatment if documentation of the reason for discontinuation of therapy is available, and was not due to inability to tolerate treatment or comply with follow up
7. Absence of extensive bridging fibrosis (≥ Metavir 3) or cirrhosis as determined by any of the following:
• A liver biopsy in the last 24 months demonstrating absence of extensive bridging fibrosis (≥ Metavir 3) or cirrhosis.
• In countries where non-invasive alternatives (eg, FibroTest, APRI, FibroScan, Magnetic Resonance Elastography or Acoustic Radiation Force Impulse Imaging) to liver biopsy are approved, two separate non-invasive tests documenting the absence of extensive bridging fibrosis (≥Metavir 3) or cirrhosis are allowed. The noninvasive alternative results must be reviewed and approved by the sponsor prior to
randomization.
o Lab tests (eg, APRI and Fibrotest) have to be performed at Screening
o Imaging tests (eg, Fibroscan, Magnetic Resonance Elastography, Acoustic Radiation Force Impulse Imaging) have to be performed within 6 months of Screening
8. 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
9. Creatinine clearance ≥ 70 mL/min.
10. Females of childbearing potential must have a negative pregnancy test at Screening and Baseline11. Females of childbearing potential must agree to complete abstinence from intercourse from three weeks prior to the first dose of study drug until 30 days following the last dose of study drug
or
Agree to use highly effective contraception (less than 1% failure rate) from three weeks prior to the first dose of study drug and for 30 days after the last dose of study medication:
• Intra-uterine devices (IUDs) (ie, Copper T 380A IUD, LNg 20 IUD)
• Tubal sterilization
• Vasectomy
• Estrogen and Progesterone
o Oral contraceptives plus male condom
o Transdermal patch plus male condom
o Vaginal ring plus male condom
• Progesterone
o Injection plus male condom
o Implant plus male condom
• Two Barrier Methods
o Female barrier (diaphragm with spermicide or cervical cap with spermicide) plus male condom
12. All male subjects must agree to consistently and correctly use a condom with intercourse while their female partner agrees to use one of the appropriate protocol accepted methods of birth control (listed above) from the date of Screening until 90 days after their last dose of study drugs
13. Male subjects must agree to refrain from sperm donation from the date of Screening until 90 days after their last dose of study drugs

Exclusion Criteria

 

Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1. Pregnant or lactating subjects.
2. Co-infection with HCV, HDV, or HIV
3. History of Gilberts disease
4. Laboratory parameters not within defined thresholds for leukopenia, neutropenia, anemia, thrombocytopenia, or clinical or other laboratory evidence of hepatic decompensation:
• White blood cell count < 2500 cell/uL
• Absolute neutrophil count (ANC) < 1,000 cells/mm3 (< 750 cells/mm3 for black or African-American subjects)
• Hemoglobin < 12 g/dL (for males), <11 g/dL (for females).
• Platelets < 100,000/mm3
• Prothrombin time ≥ 1.5 × ULN
• Albumin < 3.5 g/dL
• ALT or AST levels > 3.0 × ULN
• Direct bilirubin > 1.0 × ULN
5. Subjects with the following diseases:
• Diagnosis of autoimmune disease (eg, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, sarcoidosis, psoriasis of greater than mild severity),
• Poorly controlled diabetes mellitus
• Significant psychiatric illness (including history of severe depression, schizophrenia,
psychosis, or a history of a suicide attempt)
• Severe pulmonary disorders (eg, chronic obstructive pulmonary disease)
• Malignancy diagnosed 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 screening)
• Hemoglobinopathy
• Retinal disease
• Immunodeficiency disorders
6. Evidence of hepatocellular carcinoma (eg, α fetoprotein > 50 ng/mL or by any other standard of care measures)
7. On-going alcohol abuse in the judgment of the Investigator (eg, excessive alcohol ingestion average > 2 drinks/day or binge drinking)
8. A urine drug screen positive for illicit/illegal drugs such as current use of amphetamines, cocaine, opiates, and methadone if not on maintenance treatment (eg, morphine, heroin)
• Stable methadone or buprenorphine maintenance treatment for at least 6 months is not exclusionary
• Subjects having a positive screen for barbiturates, benzodiazepines and opiates at the Screening evaluation may be re-tested at Baseline)
9. Use of another investigational agent in the last:
• 60 days if an immunomodulator
• 30 days if a direct anti-viral small molecule
10. Receiving any of the prohibited concomitant medications listed
• Administration of any of the disallowed medications must be discontinued at least 14 days prior to the Baseline/Day 1 visit and through completion of Follow-Up Visit #2 or Early Termination Visit. Subjects who are currently taking other prescription or non-prescription medications, including herbal products, may
still be entered into the study if, in the judgment of the investigator and Sponsor, the medication will not interfere with the study procedures or compromise subject safety and/or pharmacokinetic assessments. Medications not on the list should be reviewed with the Sponsor prior to Screening. Vitamins and/or acetaminophen and/or ibuprofen and/or hormonal contraceptive medications are an exception and are allowed during the study period.

 

Prohibited Concomitant Medications    
Drug Class   Agents Disallowed To be Used with Caution
Acid Reducing Agents   H2-receptor antagonistsa
ACAT inhibitor  Avasimibe  
ACE Inhibitors  Captopril  
Anileptic  Modafinil  
Angiotensin II inhibitors  Telmisartan  
Anti -anginals  Ranolazine  
Anti-arrhythmics  Amidarone, Dronedarone, Quinidine  
Antibiotics  Azithromycin, Clarithromycin, Erythromycin, Nafcillin, Telithromycin Ciprofloxacin, Trimethoprim
Anticonvulsants  Carbamazepine, Phenytoin, Phenobarbital, Oxcarbazepine  
Antidepressants  Nefazodone  
Antiemetics    Aprepitant, Casopitant
Antifungals  Caspofungin, Ketoconazole, Itraconazole, Voriconazole, Posaconazole, Fluconazole  
Antimycobacterials  Rifampin, Rifampentine, Rifabutin, Isoniazid  
     
Beta-Blockers  Carvedilol, Talinolol  
Calcium Channel Blockers  Diltiazem, Felodipine Mibefradil, Nicardipine, Nifedipine, Nitrendipine, Verapamil  
Diuretics  Conivaptan  
Endothelin Receptor Antagonists  Bosentan  
Herbal/ Natural Supplements*  St. John’s Wort, Echinacea, Gingko, Milk thistle, Chinese herb shosaikoto (or Xiao-Shai-Hu-Tang)  
HMG-Coa Reductase Inhibitors  Atorvastatin, Cerivastatin, Lovastatin, Fluvastatin, Simvastatin Pitavastatin, Pravastatin, Rosuvastatin
Systemic Corticosteroids  All agents, including dexamethasone Use of Prednisone as a steroid burst (< or = 1 week of use) should be monitored appropriately
Systemic Chemotherapeutic (antineoplastic) Agents All agents  

a  Dose not to exceed 20 mg famotidine or equivalent