Phase 2, Multiple Ascending Dose Proof of Concept Study

A Phase 2, Randomized, Open-label, Ascending, Sequential Dose Group, Multiple Dose Study of the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of CMX157 in HBV-infected Subjects

This is a phase 2a study to evaluate the safety and tolerability of multiple oral doses of CMX157 at increasing dose levels.

Study Overview

• Status: Completed
• Conditions: Infectious Disease
• Intervention / Treatment: Drug: CMX157; Drug: TDF

Detailed Description

This is a phase 2a study to evaluate the safety and tolerability of multiple oral doses of CMX157 at increasing dose levels in hepatitis B virus(HBV) infected subjects.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Capable of giving written informed consent.
• Capable of completing study requirements.
• Chronic hepatitis B positive.
• HBV treatment naïve.

Exclusion Criteria:

• Positive result for HCV(hepatitis C virus), HDV(hepatitis D virus) or HIV(human immunodeficiency virus).
• History or medical condition that could impact patient safety.
• Current or past abuse of alcohol or illicit drugs.
• Abnormal laboratory value or ECG.
• Pregnant or breastfeeding.
• Clinical, histologic or laboratory evidence of significant liver fibrosis or cirrhosis.
• Systemic immunosuppression.
• Received an investigational drug or investigational vaccine within the 90 days prior to the first dose of study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CMX157 5mg versus TDF; CMX157, 5mg tablet, 28 days versus TDF(tenofovir disoproxil fumerate) 300mg tablet, 28 days	Drug: CMX157; tablet; Other Names: lipid conjugate TFV(tenofovir); Drug: TDF; 300mg tablet; Other Names: tenofovir disoproxil fumerate
Active Comparator: CMX157 10mg versus TDF; CMX157, 10mg tablet, 28 days versus TDF 300mg tablet, 28 days	Drug: CMX157; tablet; Other Names: lipid conjugate TFV(tenofovir); Drug: TDF; 300mg tablet; Other Names: tenofovir disoproxil fumerate
Active Comparator: CMX157 25mg versus TDF; CMX157, 25mg tablet, 28 days versus TDF 300mg tablet, 28 days	Drug: CMX157; tablet; Other Names: lipid conjugate TFV(tenofovir); Drug: TDF; 300mg tablet; Other Names: tenofovir disoproxil fumerate
Active Comparator: CMX157 50mg versus TDF; CMX157, 50mg tablet, 28 days versus TDF 300mg tablet, 28 days	Drug: CMX157; tablet; Other Names: lipid conjugate TFV(tenofovir); Drug: TDF; 300mg tablet; Other Names: tenofovir disoproxil fumerate
Active Comparator: CMX157 100mg versus TDF; CMX157, 100mg tablet, 28 days versus TDF 300mg tablet, 28 days	Drug: CMX157; tablet; Other Names: lipid conjugate TFV(tenofovir); Drug: TDF; 300mg tablet; Other Names: tenofovir disoproxil fumerate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the safety and tolerability of increasing multiple oral doses of CMX157 in HBV + patients	Capture adverse events, physical examinations, ECGs and clinical laboratory panels	28 days
To evaluate the antiviral activity of CMX157 versus tenofovir disproxil fumarate(TDF).	HBV DNA levels	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the pharmacokinetics of multiple doses of oral CMX157 in HBV + subjects, Cmax.	Measuring Cmax(concentration maximum): the peak plasma concentration.	28 days
Evaluation of the pharmacokinetics of multiple doses of oral CMX157 in HBV + subjects: Tmax.	Measuring Tmax(time maximum): the time Cmax was observed.	28 days
Evaluation of the pharmacokinetics of multiple doses of oral CMX157 in HBV + subjects: AUC.	Measuring AUC(area under the curve): area under plasma concentration versus time curve.	28 days
Evaluation of the pharmacokinetics of multiple doses of oral CMX157 in HBV + subjects: Cmin.	Measuring Cmin(concentration minimum): minimum observed plasma concentration.	28 days

Collaborators and Investigators

• Sponsor: ContraVir Pharmaceuticals, Inc.
• Investigators: Study Chair: John Sullivan-Boylai, MD, ContraVir Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Actual): July 18, 2017
• Study Completion (Actual): July 18, 2017

Study Registration Dates

• First Submitted: March 14, 2016
• First Submitted That Met QC Criteria: March 16, 2016
• First Posted (Estimate): March 17, 2016

Study Record Updates

• Last Update Posted (Actual): September 13, 2017
• Last Update Submitted That Met QC Criteria: September 12, 2017
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: chronic hepatitis B(CHB)
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Hexadecyloxypropyl 9-(2-(phosphonomethoxy)propyl)adenine
• Other Study ID Numbers: CTRV-CMX157-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes