A Phase 1b Randomized, Open Label, Active-Controlled Study to Assess the Safety, Viral Kinetics and Anti-HBV Activity of GS-7340 in Treatment-Naive Adults with Chronic Hepatitis B (CHB) Infectio

Phase 1

Completed

• Conditions: Chronic Hepatitis B (CHB) Infection; Infection - Sexually transmitted infections

• Registration Number: ACTRN12611001206910
• Lead Sponsor: Gilead Sciences, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-11-23
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1.Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
2.Must be between 18 and 65 years of age, inclusive on the date of the screening visit
3.Must have Screening plasma HBV DNA greater than or equal to 2x103 IU/mL
4.Eligible subjects must have chronic hepatitis B infection documented to be at least 6 months in duration (e.g. by positive serum HBsAg)
5.Have estimated creatinine clearance (CLCr) > 70 mL/min (using the Cockcroft-Gault method) {2202} based on serum creatinine and actual body weight as measured at the Screening evaluation, ie,:
Male:(140 – age in years) x (wt in kg) = CLCr (mL/min)
72 x (serum creatinine in mg/dL)
Female:(140 – age in years) x (wt in kg) x 0.85 = CLCr (mL/min) 72 x (serum creatinine in mg/dL)
6.A female subject is eligible to enter the study if she is:
Not pregnant or nursing
Of non-childbearing potential (i.e., women who have had a hysterectomy, have both ovaries removed or medically documented ovarian failure), or are postmenopausal – women > 50 years of age with permanent cessation of previously occurring menses greater than or equal to 12 months as a result of ovarian failure with documentation of hormonal deficiency
* Of childbearing potential (i.e., women who have not had a hysterectomy, both ovaries removed or no medically documented ovarian failure). Women greater than or equal to 50 years of age with amenorrhea will be considered to be of childbearing potential. These women must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 1 prior to randomization and agree to 1 of the following:
* Complete abstinence from intercourse from the date of Screening until 30 days following the last dose of study drugs
OR
* Consistent and correct use of 1 of the following protocol recommended methods of birth control, in addition to a male partner who correctly uses a condom from the date of Screening until 30 days after the last dose of study drugs
-implants of levonorgestrel
-injectable progesterone
-any intrauterine device (IUD) with a documented failure rate of less than 1% per year
-oral contraceptives (either combined or progesterone only), subjects should have been using this method for 3 months prior to initiating study drugs
-female barrier method: cervical cap or diaphragm
-vaginal ring
-transdermal contraceptive patch
-tubal sterilization
-vasectomy in male subject or male partner
7.All male subjects must agree to consistently and correctly use a condom while their female partner agrees to use 1 of the appropriate medically accepted methods of birth control listed above from the date of Screening until 30 days after their last dose of study drugs
8.Male subjects must agree to refrain from sperm donation for at least 60 days after the last dose
9.Subjects must refrain from blood donation from baseline/Day 1 through completion of the study and continuing for at least 30 days from date of last dose of study drug
10.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):
-ALT (SGPT) greater than or equal

Exclusion Criteria

1.Pregnant or lactating subjects
2.Receipt of anti-HBV nucleoside/nucleotide therapy. Subjects who have failed prior Interferon treatment, greater than 6 months prior to screening, are permitted to participate in the study
3.Known co-infection with HIV, HCV or HDV
4.Presence of autoimmune disorders (eg, systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis, psoriasis of greater than mild severity)
5.Have a history of liver disease other than Hepatitis B
6.Have a history of Gilbert’s Disease
7.Known or suspected cirrhosis
8.Evidence of hepatocellular carcinoma (eg, fetoprotein > 50 ng/mL or as indicated by recent ultrasound or other standard of care measure)
9.Any sign of decompensated liver disease, including prothrombin time greater than or equal to 1.5 x ULN, platelets < 100,000/mm3 or albumin < 3.5 g/dL at Screening OR current or prior history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy or variceal hemorrhage)
10.Have a history or family history of Long QT Syndrome, Wolfe-Parkinson-White Syndrome, or have a family history of sudden cardiac death or unexplained death in an otherwise healthy individual between the ages of 1 and 40 years
11.Presence or history of cardiovascular disease, cardiomyopathy, and/or cardiac conduction abnormalities
12.Have clinically relevant electrolyte abnormalities
13.History of medical or surgical treatment that permanently alters the gastric condition (eg, gastrectomy)
14.Have previously participated in an investigational trial involving administration of any investigational compound within 30 days prior to the study dosing
15.Current alcohol or substance abuse judged by the Investigator to potentially interfere with subject compliance
16.Subjects having a positive screen for amphetamines, barbiturates, cocaine, or methadone at either the Screening or baseline/day 1 visit are not permitted to participate in the study. Subjects having a positive screen for barbiturates, benzodiazepines, and/or opiates at the Screening evaluation may be re tested at baseline/Day 1. Subjects on stable methadone maintenance may be considered after discussion with the medical monitor
17.Have a history of difficulty with blood collection and/or poor venous access for the purposes of phlebotomy
18.Have consumed grapefruit, grapefruit juice, pomegranate juice or Seville orange juice within 7 days prior to Day 1
19.Known hypersensitivity to the study drugs, the metabolites or formulation excipients
20.Are unable to comply with study requirements
21.Have a history of bleeding diathesis
22.Significant bone disease, (eg, osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochrondroses), or multiple bone fractures
23.Believed by the study Investigator, to be inappropriate for study participation for any reason including any not otherwise listed. For example: renal, cardiac, hematological, hepatic, pulmonary (including chronic asthma), endocrine (eg, diabetes), central nervous, gastrointestinal (including an ulcer), vascular, metabolic (thyroid disorders, adrenal disease), immunodeficiency disorders, active infection, or malignancy that are clinically significant or requiring treatment

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary Outcome: time-weighted average change from Baseline through Week 4 (DAVG4) in serum HBV DNA (log10 IU/mL) for GS-7340 8-, 25-, 40- and 120-mg[Baseline through Week 4 on Days 1, 2, 5, 8, 10, 15, 19, 22, and 29.]