A Study Evaluating GS-9620 in Treatment Naive Subjects With Chronic Hepatitis B

NCT01590641 | Completed Phase 1 DMC

• 1 other identifier: GS-US-283-0106
• Study Type: interventional
• Target: 49
• Locations: 5 countries
• Sites: 23

Brief Summary

Dose cohorts may be dosed with one of up to 4 possible total weekly doses (0.3 mg, 1 mg, 2 mg, 4 mg). Dose escalation or repetition will be governed by pre-specified safety and activity rules. Subjects will be confined on either days 1-3 or days 1-3 and 8-10. Follow-up visits are also required periodically through day 43, and potential viral load follow-up visits at weeks 3 and 6 months post last dose. Study procedures involve blood draws for pharmacokinetic, pharmacodynamic, virologic, and safety assessments

Conditions

Hepatitis B; HBV

Keywords

Hepatitis; Hepatitis B; Hepatitis B Virus; HBV; GS-9620; Toll-like receptor (TLR)-7 Agonist

Outcome Measures

Primary Outcomes (1)

• Assessment of adverse events in single and multiple oral doses of GS-9620

  Safety will be assessed during the study through the reporting of adverse events, by clinical laboratory tests, physical examinations including vital signs and ECGs at various time points during the study, and by documentation of concomitant medications throughout the study.

  Periodically Through Week 25

Secondary Outcomes (3)

• Assessment of plasma drug concentrations of GS-9620 using non-compartmental methods

  Day 1 and Day 8

• Measurement of pharmacodynamic markers (cytokines and interferon-stimulated genes [ISGs])

  Up to Day 15

• Reduction of hepatitis B (HBV) viral load from baseline

  Up to Day 15 and Follow-Up

Study Arms (8)

0.3mg GS-9620

EXPERIMENTAL

Drug: Single Ascending Dose (SAD) Cohorts GS-9620

1mg GS-9620

EXPERIMENTAL

Drug: Single Ascending Dose (SAD) Cohorts GS-9620

2mg GS-9620

EXPERIMENTAL

Drug: Single Ascending Dose (SAD) Cohorts GS-9620

4mg GS-9620

EXPERIMENTAL

Drug: Single Ascending Dose (SAD) Cohorts GS-9620

0.3mg GS-9620 QW x 2 doses

EXPERIMENTAL

Drug: Multiple Ascending Dose (MAD) Cohorts

1mg GS-9620 QW x 2 doses

EXPERIMENTAL

Drug: Multiple Ascending Dose (MAD) Cohorts

2mg GS-9620 QW x 2 doses

EXPERIMENTAL

Drug: Multiple Ascending Dose (MAD) Cohorts

4mg GS-9620 QW x 2 doses

EXPERIMENTAL

Drug: Multiple Ascending Dose (MAD) Cohorts

Interventions

Single Ascending Dose (SAD) Cohorts GS-9620 DRUG

This study will enroll cohorts of 6 eligible, unique subjects per cohort, randomized to either active drug or placebo (5:1) within each cohort. Subjects in Single Ascending Dose (SAD) Cohorts will receive a single dose of GS-9620.

0.3mg GS-9620; 1mg GS-9620; 2mg GS-9620; 4mg GS-9620

Multiple Ascending Dose (MAD) Cohorts DRUG

This study will enroll cohorts of 6 eligible, unique subjects per cohort, randomized to either active drug or placebo (5:1) within each cohort. Subjects in Multiple Ascending Dose (MAD) Cohorts will receive GS-9620 once weekly for two weeks (QW x 2 doses)

0.3mg GS-9620 QW x 2 doses; 1mg GS-9620 QW x 2 doses; 2mg GS-9620 QW x 2 doses; 4mg GS-9620 QW x 2 doses

Eligibility Criteria

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

You may qualify if:

• Chronic HBV infection ≥ 6 months
• HBsAg ≥ 250 IU/mL
• HBV treatment naïve
• Absence of extensive bridging fibrosis (Metavir 3 or greater) or cirrhosis
• Creatinine clearance ≥ 70 mL/min

You may not qualify if:

• Co-infection with hepatitis C virus (HCV), hepatitis D virus (HDV), or HIV
• History of Gilberts disease
• Laboratory parameters not within defined thresholds for leukopenia, neutropenia, anemia, thrombocytopenia, thyroid-stimulating hormone (TSH), or other evidence of hepatic decompensation
• Diagnosis of autoimmune disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease(COPD), malignancy, hemoglobinopathy, retinal disease, or patients who are immunosuppressed
• Evidence of hepatocellular carcinoma

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (23)

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

West Coast Clinical Trials, LLC

Costa Mesa, California, 92626, United States

Location

University of California Antiviral Research Center (AVRC)

San Diego, California, 92103, United States

Location

Indiana University Medical Center

Indianapolis, Indiana, 46202-5121, United States

Location

Tulane University Health Sciences Center

New Orleans, Louisiana, 70122, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Kansas City Gastroenterology and Hepatology

Kansas City, Missouri, 64131, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

CRI Worldwide, LLC

Philadelphia, Pennsylvania, 19139, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84123, United States

Location

Nepean Hospital

Kingswood, New South Wales, 2747, Australia

Location

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

Location

Monash University, Department of Medicine

Clayton, Victoria, 3168, Australia

Location

Royal Perth Hospital

Nedlands, Western Australia, 6009, Australia

Location

University of Calgary, Heritage Medical Research Center

Calgary, Alberta, T2N 4Z6, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Algorithme Pharma, Inc.

Montreal, Quebec, H3P 3P1, Canada

Location

Auckland Clinical Studies

Grafton, Auckland, 1142, New Zealand

Location

Asan Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

MeSH Terms

Conditions

Hepatitis B; Hepatitis

Interventions

Sagittal Abdominal Diameter; mycophenolic adenine dinucleotide; Cohort Studies

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Body Size; Body Weights and Measures; Body Constitution; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Anthropometry; Investigative Techniques; Physiological Phenomena; Epidemiologic Studies; Epidemiologic Study Characteristics; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Benedetta Massetto, M.D.

  Gilead Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2012
• First Posted: May 3, 2012
• Study Start: April 1, 2012
• Primary Completion: September 1, 2013
• Study Completion: October 1, 2013
• Last Updated: November 14, 2013

Record last verified: 2013-11

Locations

AU (4); CA (3); NZ (1); US (13); KR (2)